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Tumor marker in market
ABSTRACT
Tumor Markers include a wide range of biomacromolecules orchestrated in abundance fixation
by a wide assortment of neoplastic cells. The markers could be endogenous results of
exceptionally dynamic metabolic threatening cells or the results of recently turned on qualities,
which stayed unexpressed in early life or recently obtained antigens at cell and sub-cell levels.
The presence of tumor marker and their focus are identified with the beginning and development
of dangerous tumors in patients. A perfect tumor marker ought to be profoundly delicate,
explicit, dependable with high prognostic worth, organ particularity and it should relate with
tumor stages. Be that as it may, none of the tumor markers answered to date has every one of
these attributes. Inspite of these impediments, numerous tumor markers have indicated incredible
clinical significance in checking adequacy of various methods of treatments during whole course
of sickness in malignant growth patients. Moreover, assurance of markers additionally helps in
early discovery of malignant growth repeat and in anticipation.
Introduction :
Tumor Markers are biochemical substances expounded by tumor cells either because of the
reason or impact of dangerous process. These markers can be ordinary endogenous items that are
delivered at a more prominent rate in disease cells or the results of recently turned on qualities
that stayed tranquil in the ordinary cells. A tumor marker created by the tumor what's more,
when present in noteworthy sums, demonstrates the nearness of a malignant growth. They might
be available as intracellular substances in tissues or might be discharged into the flow also,
show up in serum . Proceeding with scan for reasonable tumor markers in serum, tissue and body
liquids during neoplastic procedure is of clinical incentive in the administration of patients with
different malignancies. 1
The range of biochemical tumor markers answered to date is wide. Tumor markers can be
comprehensively delegated
1. Oncofetal antigens (for example alpha-fetoprotein (AFP), Carcinoembryonic antigen (CEA),
Pancreatic oncofetal antigen, fetal sulfoglycoprotein.
2. Tumor related antigens/Cancer Antigens for example CA125, CA19-9, CA15-3, CA72-4
CA50 and so forth.
3. Hormones for example Beta human chorionic gonadotropin, calcitonin, placental lactogen and
so forth.
4. Hormone receptors (for example estrogen and progesterone receptors)
5. Compounds and Isoenzymes (for example prostate explicit antigen (PSA), prostatic corrosive
phosphatase (PAP), neuron explicit enolase (NSE), glycosyl transferases, placental antacid
phosphatase (PALP), terminal deoxy nucleotidyl transferase (TDT), lysozyme, alpha amylase
6. Serum and tissue proteins (beta-2 microglobulin, monoclonal immunoglobulin/para proteins,
glial fibrillary acidic protein (GFAP), protein S-100, ferritin, fibrinogen corruption items)
7. Different biomolecules for example polyamines .
A perfect tumor marker hypothetically ought to have the accompanying measures 2
1. It should be profoundly delicate and ought to have low bogus negatives.
2. It ought to be profoundly explicit and ought to have low bogus positive.
3. It should have high positive and negative prescient esteem.
4. 100% precision in separating between sound people and tumor patients.
5. It ought to have the option to separate between neoplastic also, non-neoplastic malady and
show positive relationship with tumor volume and degree.
6. It ought to anticipate early repeat and have prognostic esteem.
7. It should be clinically delicate for example distinguishable at ahead of schedule phase of
tumor.
8. Its levels ought to be going before the neoplastic procedure, so it ought to be valuable for
screening early malignancy.
9. It ought to be either a widespread marker for a wide range of malignancies or explicit to one
sort of threat.
Tumor markers in routine use which will discuss it in details
table 1 :
Marker Cancer
CA15-3, BR 27.29 Breast
CEA, CA 19-9 Colorectal
CA 72.4, CA 19-9, CEA Gastric
NSE, CYFA 21.1 Lung
PSA, PAP Prostate
CA 125 Ovarian
Calcitonin, thyroglobulin Thyroid
hCG Trophoblastic
CA 19-9, CEA Pancreatic
AFP, CA 19-1 Hepatocellular
BAP, Osteocalcin, NTx Bone
Catecholamines, metabolites Pheochromocytoma
Fecal occult blood Colon cancer
ALPHA FETOPROTEIN (AFP)3
AFP, a very popular and extensively studied carcinoembryonic glycoprotein / Oncofetal antigen,
is a major fetal serum globulin with a molecular weight of approximately 65,000. The single
chain glycoprotein has carbohydrate content of 3% and amino acid sequence similar to that of
albumin. It is expressed either during malignancy or during intra uterine or early postnatal
life and Elevated in pregnancy, liver disease (hepatitis, cirrhosis,GI tumors), AFP level not
directly related to tumor size.
THE ROLE OF AFP IN MALIGNANCY
Serum AFP estimation is of significant clinical guide in conclusion, guess and checking essential
hepatocellular carcinoma , hepatoblastoma, non-seminomatous testicular germ cell tumors the
embryonal carcinoma, teratomas, choriocarcinoma and yolk sac carcinoma and so on , germ
cell tumors of ovary and extragonadal germ cell tumors . Roughly 60-90% of patients with
essential hepatocellular carcinoma have serum AFP focuses in excess of 500 ng/ml.
Hepatoblastoma; an undeveloped structure has consistently been seen as related with terribly
raised serum AFP levels. The level of fucosylation of AFP is answered to be a valuable
parameter for early identification of hepatocellular carcinoma. The serum AFP estimations may
be valuable as a touchy marker framework for the early identification of repeating hepatocellular
carcinoma, even before the clinical manifestations are obvious
. HUMAN CHORIONIC GONADOTROPIN (βHCG)
HCG, A marker of germ cell tumors and trophoblastic illness, is 45KD glycoprotein, made out of
two unique subunits the alpha chain (14 KD) and beta chain (24KD). It contains 30 % sugar. The
beta subunit decides the immunological and hormone explicitness. HCG is orchestrated by the
synctiotrophoblasts of the placenta during pregnancy. The pinnacle HCG fixation is reached
between tenth and twelfth long stretches of incubation. The reference esteems in serum of solid
men and non-pregnant ladies are under 5 IU/ml and post-menopausal ladies are under 10 IU/ml
HCG is a marker of first decision for gonadal (testicles and ovary) choriocarcinoma and
extragonadal choriocarcinoma. HCG shows 100 % affectability for choriocarcinoma
independent of their site notwithstanding hydatidiform mole. In testicular tumors, the location
of HCG and AFP corresponds with the histological discoveries, and is thusly pivotal for the
restorative strategies with the utilization of sequential assurance of βhCG, the biochemical
repeat goes before by 3 months before the patient has manifestations of clinical
repeat/metastases.
CARCINO-EMBYRIONIC ANTIGEN (CEA)4
CEA 150-300 kDa glycoprotein, Elevated in smokers and elderly , Elevated in breast, pancreatic,
GI, and lung cancer, Breast cancer: used for detecting and monitoring
metastatic disease , Elevated in benign diseases: cirrhosis, emphysema & rectal polyps , CEA –
Not useful for CRC Screening , New more specific marker for CRC: TIMP-1 (Tissue
inhibitor of metalloprotease)
Ensuing advancement of a radioimmunoassay (RIA) made it conceivable to distinguish
exceptionally low groupings of CEA in blood, other body liquids, and furthermore in typical and
infected tissues. It is discharged by certain undeveloped and grown-up tissues notwithstanding
adenocarcinoma of the stomach related organs. Broad investigations of patients bearing essential
and metastatic colorectal neoplasms have confirmed that its essential use is in the discovery of
nearby and metastatic malignant growth repeat after beginning resection of the essential tumor,
through intermittent postoperative investigation of CEA in serum or plasma.
PROSTATE SPECIFIC ANTIGEN (PSA) 5
Prostate explicit antigen (PSA) named prior as gammasemino protein because of its essence in
fundamental plasma. PSA is 34 KD single chain glycoprotein comprising of 93% amino acids
what's more, 7% sugar. It is a monomer comprised of 240 amino corrosive buildups. PSA, an
impartial serine protease, having chymotrypsin and trypsin like exercises has a place with
glandular kallikrein family. Prostate epithelium orchestrates PSA and productively forestalls the
departure of the protease into the dissemination. In any case, minor sum PSA enters into the
blood course. PSA is known to shape edifices with diverse protease inhibitors in serum just as in
original liquid and consequently different atomic structures are known to flow in blood. The 100
KD PSA-ACT complex remains the major immunoreactive type of PSA establishing 80-90%
of complete PSA n serum. The edifices of PSA with other serine protease inhibitors
(SERPINES) are PSA-AT (alpha-1 antitrypsin) PSAPCI (protease C inhibitor).
The PSA-AT and PSA-PCI happen at much lower focuses in serum representing less than 1% of
absolute edifices. Alpha-2 macroglobulin (α2M) too structures complex with PSA. Because of
extremely huge sub-atomic weight the α 2M exemplifies the entire PSA atom coming about in
concealing of all epitopes on PSA atom. The conceal epitopes forestall immunodetection of PSA
in this complex during routine chemical immunoassays. The staying free PSA comprised roughly
5-15% of the aggregate immunoreactive structures.
Prostate specific antigen clinical applications :
Early detection in conjunction with DRE , Determine success of radical prostatectomy
, Recurrence following treatment , Monitoring hormonal treatment.
PROSTATE ACID PHOSPHATASE (PAP) 6
Corrosive phosphatase action is multiple times progressively copious in prostate tissue than in
some other tissue. Corrosive phosphatase prostatic portion is helpful just in organizing evidently
limited illness i.e., essential prostate malignant growth before conclusive treatment for example,
radical prostatectomy. Its movement in serum can be evaluated by a few manufactured
substrates, however now explicit antibodies are accessible for immunoassays. The enzymatic test
seems better than the immunoassay in this unique circumstance. Enthusiasm for corrosive
phosphatase tests in serum as a measure of prostatic disease organizing has diminished with the
accessibility of the more touchy and explicit PSA examine.
CANCER ANTIGEN 25 (CA 125)
CA 125, a tumor related glycoprotein of more than 200 KD, Increased in benign diseases:
pregnancy, endometriosis,ovarian cysts, PID, cirrhosis, hepatitis, pericarditis Increased in other
cancers: lung, breast, GI, endometrial,& pancreaticwas identified by utilizing murine monoclonal
immunizer OC 125 produced by vaccination against histologically well characterized ovarian
adenocarcinoma cell line. OC 125 monoclonal immune response perceives numerous rehashing
antigenic determinants on a high sub-atomic weight glycoprotein. These epitopes are likewise
recognized in fetal coelomic epithelium, mullerian conduit remainders, amnion and amniotic
liquid, fetal and grown-up ordinary tracheal, bronchial, bronchiolar and terminal bronchiolar
epithelium . CA 125 antigenic determinants are most certainly not found in ordinary grown-up
ovarian tissues however are related with epithelial ovarian carcinoma. Raised CA 125 focuses
are found in the serum, milk and cervical discharges of pregnant ladies. Evidently solid ladies
with no ovarian mass (favorable or threatening) show CA 125 levels less than 35 u/ml in their
serum and all around, this worth was picked as the cut off worth, for example furthest constraint
of ordinary range.
CA 19-9 (CANCER ANTIGEN 19-9)
CA 19-9 is a tumor marker of first decision for malignant growth pancreas furthermore,
malignant growth nerve bladder. The marker is 210 KD tumor related glycoprotein antigen
present as sugar determinant on glycolipid and glycoprotein. CA 19-9 is portrayed by
monoclonal counter acting agent 1116 - NS 19-9 by inoculating BALB/c mice with human
colorectal malignancy line. This counter acting agent responds with a starch antigenic
determinant (CA 19-9) which has been recognized as a sialylated lacto-Nfucopentaose II, an
oligosaccharide sharing basic highlights with Lewis blood bunch substances. The antigen was
confined immunohistologically on fetal epithelia of the colon, little digestive system, stomach,
pancreas and liver and exceptionally little fixations on grown-up gastrointestinal tract and lung
tissue. CA-19-9 are highest for the adenocarcinoma pancreas. Sensitivity of 70 % is observed in
cholangio carcinomas and gallbladder carcinomas.
CA 15-3/CA27.297
• High molecular weight glycoprotein (Polymorphic Epithelial Mucin) • Breast cancer marker •
Elevated in benign diseases of liver & breast • Elevated in other cancers: pancreatic, lung,
ovarian, colorectal, & liver
BETA - 2 MICROGLOBULIN (β2M)
β2M is 11 KD light chain constituent of HLA antigen. The Beta 2 M is utilized clinically as a
marker of first decision for B-cell leukemia, lymphomas and numerous Myeloma. Be that as it
may, due to its non-particularity its moderate rise is seen in cases of strong tumors and
furthermore in different fiery sicknesses, considerate irresistible issue, and essential biliary
cirrhosis and in AIDS. It is utilized routinely for assessing tumor cell load, illness action and
visualization. It is likewise used to screen adequacy of patient's reaction to treatment. Raised
degrees of Beta 2 – M are likewise announced in cerebrospinal liquid (CSF), focal nerves
framework (CNS) Mets, intense lymphobalstic leukemia, Lymphoma and other
Lymphoproliferative scatters/sicknesses.
CYTOKERATINS / KERATINS
CYFRA 21-1
Cyfra 21-1 is an antigenic determinant present on 40 KD protein the cytokeratin 19. This antigen
is defined by using two mouse monoclonal antibodies the KS 19-1 and BM 19-21 by
immunization against MCF – 7cell line. This antigen is expressed in normal, simple epithelium
as well as in proliferating epithelium. It is also defined by using monoclonal antibody, which
detects specific epitopes on cytokeratin 19. Cyfra 21-1 is used as a tumor marker for non-small
cell lung cancer (NSCLC), such as squamous cell carcinoma (SCC), adenocarcinoma and large
cell carcinomas.
CALCITONIN
Calcitonin, a low sub-atomic weight circling peptide hormone, integrated by C cells of the
thyroid is utilized as tumor markers as its expanded focus is accounted for in malignancies with
skeletal metastases. Serum calcitonin fixations are too answered to increment in medullary
carcinoma of the thyroid, Bronchogenic carcinoma, little cell lung malignant growth, bosom,
liver, lung, renal malignant growths and carcinoid tumors
CATECHOLAMINES 8
Plasma and urinary norepinephrin and epinephrine levels are expanded especially in
Pheochromocytoma
EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)
EGFR a 170 KD, glycoprotein ties to epidermal development factor (EGF) with high proclivity
and shows huge grouping homology with V-erbD oncogene item. EGFR quality over articulation
is seen in SCC. EGFR levels are brought up in bosom malignancy, gliomas, lung disease, blood
malignancy, SCC and tumors of female genital tract. The bosom malignancy patients with
positive EGFR for answered to have diminished backslide free endurance. Nonattendance of
EGFR shows a decent reaction to tamoxifan treatment .
ESTROGEN RECEPTOR (ER), PROGESTERON RECEPTOR (PR)
ER a 70 KD protein is available in cores of mammary and uterine tissues. ER and PR have a
place with receptor super quality family counting receptors for thyroid hormone, nutrient D3 and
retinoic corrosive. In bosom tumor patients the ER and PR estimations help in recognizing the
patients liable to accomplish profit by endocrine treatment, 55% to 60% ER positive essential
malignancies of bosoms demonstrate great reaction to hormone treatment. Following
mastectomy, the patient with high convergences of ER and PR positive harmful tumors have
longer sickness free endurance contrasted with patients with low levels of the two receptors. PR
is a more touchy marker than ER in anticipating viable responsiveness to endocrine treatment in
bosom tumor patients ..
HOMOVANILLIC ACID (HVA) AND VANILLYMANDELIC (VMA)
HVA and VMA are acidic metabolites of catecholamine. Their expanded discharge is seen in
patients with neural peak tumors. Assurance of VMA and HVA additionally helps in recognizing
what's more, observing treatment in patients of Pheochromocytoma. Their estimations are
additionally pertinent for neuroblastomas
HYDROXY INDOLE ACETIC ACID (5-HIAA) 9
Urinary HIAA estimation is utilized clinically and aides in determination of indole discharging
tumors. Its focus too expanded in patients with carcinoid tumors. HIAA is routinely utilized for
observing adequacy of carcinoid condition treatment.
INTERLEUKIN-2 RECEPTOR/TAC ANTIGEN (IL-2R)
IL-2 α developed receptor, a 55 KD glycosylated protein is finished communicated in certain
sorts of lymphoid malignancies. Serum levels of IL-2 are raised in grown-up T-cell leukemia and
the marker additionally helps in checking treatment in these patients.
LIPID-ASSOCIATED SIALIC ACID IN PLASMA (LASA-P)
Expanded centralization of LASA-P is accounted for in numerous malignancies, for example,
bosom, gastrointestinal tract, lung, leukemia, lymphoma, Hodgkin's sicknesses and melanoma.
The slight increment of this marker is additionally seen in a few provocative maladies
demonstrating its poor particularity. The affectability of this marker shifts from 77% to 97% for
various tumors.
TUMOR SUPPRESSOR GENE P53
P53, a 53 KD atomic phosphoprotein works as tumor silencer by hindering cell multiplication.
P53 plays a predominant job in cell apoptosis. P53 quality changes are accounted for in roughly
half of a wide range of tumors. Regularly happening P53 quality changes are accounted for in
essential bosom, colon, ovarian, lung, and esophageal carcinomas.
SQUAMOUS CELL CARCINOMA (SCC) ANTIGEN 10
SCC antigen, a 48 KD protein, is filtered from uterine cervix The antigen fixation is raised or in
squamous cell carcinomas of head and neck, lung, throat and butt-centric channel. The most
elevated grouping of SCC antigen is found in patients with metastases. The marker rise is
additionally seen in 70% patients with cutting edge cervical malignancies. Sequential serum
SCC antigen assurance helps in deciding movement furthermore, relapse of cervical malignant
growth following chemotherapy. The antigen levels are likewise brought up in certain patients of
broad liver ailment. The joined utilization of CEA, NSE and SCC antigen has helped in
expanding affectability for location and observing of lung tumors .
MONOCLONAL IMMUNOGLOBULIN/PARAPROTEIN
Monoclonal immunoglobulin content is of extraordinary incentive in determination just as for
observing adequacy of remedial the executives of plasma cell neoplasms specifically numerous
Myeloma, Waldenstrom's macroglobulinemia, plasmacytoma, B cell leukaemias and
lymphomas(100-104). Ongoing distribution by Yilmaz and his group from Turkey have
underscored the requirement for reasonable utilization of tumor markers following the act of
proof based medication. It is unnecessary to express that inspite of non-explicitness of wide
range of tumor markers accessible today, their potential job in checking whole malignant growth
helpful course is exceptionally significant clinically.
conclusion:
Inspite of these impediments, numerous tumor markers have indicated incredible clinical
significance in checking adequacy of various methods of treatments during whole course of
sickness in malignant growth patients. Moreover, assurance of markers additionally helps in
early discovery of malignant growth repeat and in anticipation.
References :
1-Bates SE, Longo DL. Use of serum tumor markers in cancer diagnosis and management.
Semin. Oncol 1987; 14: 102-38.
2. Paterson AJ, Schlom J, Seares HF. A radioimmunoassayfor the detection of a human tumor-
associated glycoprotein(TAG 72) using monoclonal antibody B 72-3. Int J Cancer1986; 37:659-
66.
3. Esteva FJ, Hortobagyi GN. Prognostic molecular markers in early breast cancer. Breast
Cancer Res 2004; 6:109–18.
4. Fitzgeralk MG, MacDonald DJ, Krainer MG. BRCA1 mutations in Jewish women with early
onset breast cancer. N Engl J Med 1996; 334:143-9.
5. Del Villano BC, Brennan S, Brock P. Radioimmunometric assay for monoclonal antibody-
defined tumor marker CA 19-9. Clin Hem 1983; 29:549-52.
6. Bhattacharya S, Siegel ER, Petersen GM, Chari ST, Suva L, Haun RS. Diagnosis of Pancreatic
Cancer Using Serum Proteomic Profiling. Neoplasia 2004; 6:674–86.
7. Paterson AJ, Schlom J, Seares HF. A radioimmunoassay for the detection of a human tumor-
associated glycoprotein (TAG 72) using monoclonal antibody B 72-3. Int J Cancer
1986; 37:659-66.
8. William MS, Richard G, Kimberly KA, Jerry G, Scott HK, William FS, Philip PT.
Comparison of the Sensitivity and Specificity of the CA 19-9 and Carcinoembryonic Antigen
assays in detecting cancer of the Pancreas.Gastroenterology 1986; 90:343-9.
9. Kurman RJ, Norris HJ. Endodermal sinus tumor of the ovary : A clinical and pathological
analysis of 71 cases. Cancer 1976; 38:2404-19
10. Alpert E, Doysdale JW, Isselbacher KJ. Human alphafetoprotein: isolation, characterisation
and demonstration of microheterogeneity. J Biol Chem 1972; 247: 3792-8

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Tumor markers in market

  • 1. Tumor marker in market ABSTRACT Tumor Markers include a wide range of biomacromolecules orchestrated in abundance fixation by a wide assortment of neoplastic cells. The markers could be endogenous results of exceptionally dynamic metabolic threatening cells or the results of recently turned on qualities, which stayed unexpressed in early life or recently obtained antigens at cell and sub-cell levels. The presence of tumor marker and their focus are identified with the beginning and development of dangerous tumors in patients. A perfect tumor marker ought to be profoundly delicate, explicit, dependable with high prognostic worth, organ particularity and it should relate with tumor stages. Be that as it may, none of the tumor markers answered to date has every one of these attributes. Inspite of these impediments, numerous tumor markers have indicated incredible clinical significance in checking adequacy of various methods of treatments during whole course of sickness in malignant growth patients. Moreover, assurance of markers additionally helps in early discovery of malignant growth repeat and in anticipation. Introduction : Tumor Markers are biochemical substances expounded by tumor cells either because of the reason or impact of dangerous process. These markers can be ordinary endogenous items that are delivered at a more prominent rate in disease cells or the results of recently turned on qualities that stayed tranquil in the ordinary cells. A tumor marker created by the tumor what's more, when present in noteworthy sums, demonstrates the nearness of a malignant growth. They might be available as intracellular substances in tissues or might be discharged into the flow also, show up in serum . Proceeding with scan for reasonable tumor markers in serum, tissue and body liquids during neoplastic procedure is of clinical incentive in the administration of patients with different malignancies. 1 The range of biochemical tumor markers answered to date is wide. Tumor markers can be comprehensively delegated 1. Oncofetal antigens (for example alpha-fetoprotein (AFP), Carcinoembryonic antigen (CEA), Pancreatic oncofetal antigen, fetal sulfoglycoprotein. 2. Tumor related antigens/Cancer Antigens for example CA125, CA19-9, CA15-3, CA72-4 CA50 and so forth. 3. Hormones for example Beta human chorionic gonadotropin, calcitonin, placental lactogen and so forth. 4. Hormone receptors (for example estrogen and progesterone receptors) 5. Compounds and Isoenzymes (for example prostate explicit antigen (PSA), prostatic corrosive phosphatase (PAP), neuron explicit enolase (NSE), glycosyl transferases, placental antacid phosphatase (PALP), terminal deoxy nucleotidyl transferase (TDT), lysozyme, alpha amylase 6. Serum and tissue proteins (beta-2 microglobulin, monoclonal immunoglobulin/para proteins, glial fibrillary acidic protein (GFAP), protein S-100, ferritin, fibrinogen corruption items) 7. Different biomolecules for example polyamines . A perfect tumor marker hypothetically ought to have the accompanying measures 2
  • 2. 1. It should be profoundly delicate and ought to have low bogus negatives. 2. It ought to be profoundly explicit and ought to have low bogus positive. 3. It should have high positive and negative prescient esteem. 4. 100% precision in separating between sound people and tumor patients. 5. It ought to have the option to separate between neoplastic also, non-neoplastic malady and show positive relationship with tumor volume and degree. 6. It ought to anticipate early repeat and have prognostic esteem. 7. It should be clinically delicate for example distinguishable at ahead of schedule phase of tumor. 8. Its levels ought to be going before the neoplastic procedure, so it ought to be valuable for screening early malignancy. 9. It ought to be either a widespread marker for a wide range of malignancies or explicit to one sort of threat. Tumor markers in routine use which will discuss it in details table 1 : Marker Cancer CA15-3, BR 27.29 Breast CEA, CA 19-9 Colorectal CA 72.4, CA 19-9, CEA Gastric NSE, CYFA 21.1 Lung PSA, PAP Prostate CA 125 Ovarian Calcitonin, thyroglobulin Thyroid hCG Trophoblastic CA 19-9, CEA Pancreatic AFP, CA 19-1 Hepatocellular BAP, Osteocalcin, NTx Bone Catecholamines, metabolites Pheochromocytoma Fecal occult blood Colon cancer ALPHA FETOPROTEIN (AFP)3 AFP, a very popular and extensively studied carcinoembryonic glycoprotein / Oncofetal antigen, is a major fetal serum globulin with a molecular weight of approximately 65,000. The single chain glycoprotein has carbohydrate content of 3% and amino acid sequence similar to that of albumin. It is expressed either during malignancy or during intra uterine or early postnatal life and Elevated in pregnancy, liver disease (hepatitis, cirrhosis,GI tumors), AFP level not directly related to tumor size. THE ROLE OF AFP IN MALIGNANCY Serum AFP estimation is of significant clinical guide in conclusion, guess and checking essential hepatocellular carcinoma , hepatoblastoma, non-seminomatous testicular germ cell tumors the embryonal carcinoma, teratomas, choriocarcinoma and yolk sac carcinoma and so on , germ
  • 3. cell tumors of ovary and extragonadal germ cell tumors . Roughly 60-90% of patients with essential hepatocellular carcinoma have serum AFP focuses in excess of 500 ng/ml. Hepatoblastoma; an undeveloped structure has consistently been seen as related with terribly raised serum AFP levels. The level of fucosylation of AFP is answered to be a valuable parameter for early identification of hepatocellular carcinoma. The serum AFP estimations may be valuable as a touchy marker framework for the early identification of repeating hepatocellular carcinoma, even before the clinical manifestations are obvious . HUMAN CHORIONIC GONADOTROPIN (βHCG) HCG, A marker of germ cell tumors and trophoblastic illness, is 45KD glycoprotein, made out of two unique subunits the alpha chain (14 KD) and beta chain (24KD). It contains 30 % sugar. The beta subunit decides the immunological and hormone explicitness. HCG is orchestrated by the synctiotrophoblasts of the placenta during pregnancy. The pinnacle HCG fixation is reached between tenth and twelfth long stretches of incubation. The reference esteems in serum of solid men and non-pregnant ladies are under 5 IU/ml and post-menopausal ladies are under 10 IU/ml HCG is a marker of first decision for gonadal (testicles and ovary) choriocarcinoma and extragonadal choriocarcinoma. HCG shows 100 % affectability for choriocarcinoma independent of their site notwithstanding hydatidiform mole. In testicular tumors, the location of HCG and AFP corresponds with the histological discoveries, and is thusly pivotal for the restorative strategies with the utilization of sequential assurance of βhCG, the biochemical repeat goes before by 3 months before the patient has manifestations of clinical repeat/metastases. CARCINO-EMBYRIONIC ANTIGEN (CEA)4 CEA 150-300 kDa glycoprotein, Elevated in smokers and elderly , Elevated in breast, pancreatic, GI, and lung cancer, Breast cancer: used for detecting and monitoring metastatic disease , Elevated in benign diseases: cirrhosis, emphysema & rectal polyps , CEA – Not useful for CRC Screening , New more specific marker for CRC: TIMP-1 (Tissue inhibitor of metalloprotease) Ensuing advancement of a radioimmunoassay (RIA) made it conceivable to distinguish exceptionally low groupings of CEA in blood, other body liquids, and furthermore in typical and infected tissues. It is discharged by certain undeveloped and grown-up tissues notwithstanding adenocarcinoma of the stomach related organs. Broad investigations of patients bearing essential and metastatic colorectal neoplasms have confirmed that its essential use is in the discovery of nearby and metastatic malignant growth repeat after beginning resection of the essential tumor, through intermittent postoperative investigation of CEA in serum or plasma. PROSTATE SPECIFIC ANTIGEN (PSA) 5 Prostate explicit antigen (PSA) named prior as gammasemino protein because of its essence in fundamental plasma. PSA is 34 KD single chain glycoprotein comprising of 93% amino acids what's more, 7% sugar. It is a monomer comprised of 240 amino corrosive buildups. PSA, an impartial serine protease, having chymotrypsin and trypsin like exercises has a place with
  • 4. glandular kallikrein family. Prostate epithelium orchestrates PSA and productively forestalls the departure of the protease into the dissemination. In any case, minor sum PSA enters into the blood course. PSA is known to shape edifices with diverse protease inhibitors in serum just as in original liquid and consequently different atomic structures are known to flow in blood. The 100 KD PSA-ACT complex remains the major immunoreactive type of PSA establishing 80-90% of complete PSA n serum. The edifices of PSA with other serine protease inhibitors (SERPINES) are PSA-AT (alpha-1 antitrypsin) PSAPCI (protease C inhibitor). The PSA-AT and PSA-PCI happen at much lower focuses in serum representing less than 1% of absolute edifices. Alpha-2 macroglobulin (α2M) too structures complex with PSA. Because of extremely huge sub-atomic weight the α 2M exemplifies the entire PSA atom coming about in concealing of all epitopes on PSA atom. The conceal epitopes forestall immunodetection of PSA in this complex during routine chemical immunoassays. The staying free PSA comprised roughly 5-15% of the aggregate immunoreactive structures. Prostate specific antigen clinical applications : Early detection in conjunction with DRE , Determine success of radical prostatectomy , Recurrence following treatment , Monitoring hormonal treatment. PROSTATE ACID PHOSPHATASE (PAP) 6 Corrosive phosphatase action is multiple times progressively copious in prostate tissue than in some other tissue. Corrosive phosphatase prostatic portion is helpful just in organizing evidently limited illness i.e., essential prostate malignant growth before conclusive treatment for example, radical prostatectomy. Its movement in serum can be evaluated by a few manufactured substrates, however now explicit antibodies are accessible for immunoassays. The enzymatic test seems better than the immunoassay in this unique circumstance. Enthusiasm for corrosive phosphatase tests in serum as a measure of prostatic disease organizing has diminished with the accessibility of the more touchy and explicit PSA examine. CANCER ANTIGEN 25 (CA 125) CA 125, a tumor related glycoprotein of more than 200 KD, Increased in benign diseases: pregnancy, endometriosis,ovarian cysts, PID, cirrhosis, hepatitis, pericarditis Increased in other cancers: lung, breast, GI, endometrial,& pancreaticwas identified by utilizing murine monoclonal immunizer OC 125 produced by vaccination against histologically well characterized ovarian adenocarcinoma cell line. OC 125 monoclonal immune response perceives numerous rehashing antigenic determinants on a high sub-atomic weight glycoprotein. These epitopes are likewise recognized in fetal coelomic epithelium, mullerian conduit remainders, amnion and amniotic liquid, fetal and grown-up ordinary tracheal, bronchial, bronchiolar and terminal bronchiolar epithelium . CA 125 antigenic determinants are most certainly not found in ordinary grown-up ovarian tissues however are related with epithelial ovarian carcinoma. Raised CA 125 focuses are found in the serum, milk and cervical discharges of pregnant ladies. Evidently solid ladies with no ovarian mass (favorable or threatening) show CA 125 levels less than 35 u/ml in their serum and all around, this worth was picked as the cut off worth, for example furthest constraint
  • 5. of ordinary range. CA 19-9 (CANCER ANTIGEN 19-9) CA 19-9 is a tumor marker of first decision for malignant growth pancreas furthermore, malignant growth nerve bladder. The marker is 210 KD tumor related glycoprotein antigen present as sugar determinant on glycolipid and glycoprotein. CA 19-9 is portrayed by monoclonal counter acting agent 1116 - NS 19-9 by inoculating BALB/c mice with human colorectal malignancy line. This counter acting agent responds with a starch antigenic determinant (CA 19-9) which has been recognized as a sialylated lacto-Nfucopentaose II, an oligosaccharide sharing basic highlights with Lewis blood bunch substances. The antigen was confined immunohistologically on fetal epithelia of the colon, little digestive system, stomach, pancreas and liver and exceptionally little fixations on grown-up gastrointestinal tract and lung tissue. CA-19-9 are highest for the adenocarcinoma pancreas. Sensitivity of 70 % is observed in cholangio carcinomas and gallbladder carcinomas. CA 15-3/CA27.297 • High molecular weight glycoprotein (Polymorphic Epithelial Mucin) • Breast cancer marker • Elevated in benign diseases of liver & breast • Elevated in other cancers: pancreatic, lung, ovarian, colorectal, & liver BETA - 2 MICROGLOBULIN (β2M) β2M is 11 KD light chain constituent of HLA antigen. The Beta 2 M is utilized clinically as a marker of first decision for B-cell leukemia, lymphomas and numerous Myeloma. Be that as it may, due to its non-particularity its moderate rise is seen in cases of strong tumors and furthermore in different fiery sicknesses, considerate irresistible issue, and essential biliary cirrhosis and in AIDS. It is utilized routinely for assessing tumor cell load, illness action and visualization. It is likewise used to screen adequacy of patient's reaction to treatment. Raised degrees of Beta 2 – M are likewise announced in cerebrospinal liquid (CSF), focal nerves framework (CNS) Mets, intense lymphobalstic leukemia, Lymphoma and other Lymphoproliferative scatters/sicknesses. CYTOKERATINS / KERATINS CYFRA 21-1 Cyfra 21-1 is an antigenic determinant present on 40 KD protein the cytokeratin 19. This antigen is defined by using two mouse monoclonal antibodies the KS 19-1 and BM 19-21 by immunization against MCF – 7cell line. This antigen is expressed in normal, simple epithelium as well as in proliferating epithelium. It is also defined by using monoclonal antibody, which detects specific epitopes on cytokeratin 19. Cyfra 21-1 is used as a tumor marker for non-small cell lung cancer (NSCLC), such as squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinomas. CALCITONIN Calcitonin, a low sub-atomic weight circling peptide hormone, integrated by C cells of the thyroid is utilized as tumor markers as its expanded focus is accounted for in malignancies with
  • 6. skeletal metastases. Serum calcitonin fixations are too answered to increment in medullary carcinoma of the thyroid, Bronchogenic carcinoma, little cell lung malignant growth, bosom, liver, lung, renal malignant growths and carcinoid tumors CATECHOLAMINES 8 Plasma and urinary norepinephrin and epinephrine levels are expanded especially in Pheochromocytoma EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EGFR a 170 KD, glycoprotein ties to epidermal development factor (EGF) with high proclivity and shows huge grouping homology with V-erbD oncogene item. EGFR quality over articulation is seen in SCC. EGFR levels are brought up in bosom malignancy, gliomas, lung disease, blood malignancy, SCC and tumors of female genital tract. The bosom malignancy patients with positive EGFR for answered to have diminished backslide free endurance. Nonattendance of EGFR shows a decent reaction to tamoxifan treatment . ESTROGEN RECEPTOR (ER), PROGESTERON RECEPTOR (PR) ER a 70 KD protein is available in cores of mammary and uterine tissues. ER and PR have a place with receptor super quality family counting receptors for thyroid hormone, nutrient D3 and retinoic corrosive. In bosom tumor patients the ER and PR estimations help in recognizing the patients liable to accomplish profit by endocrine treatment, 55% to 60% ER positive essential malignancies of bosoms demonstrate great reaction to hormone treatment. Following mastectomy, the patient with high convergences of ER and PR positive harmful tumors have longer sickness free endurance contrasted with patients with low levels of the two receptors. PR is a more touchy marker than ER in anticipating viable responsiveness to endocrine treatment in bosom tumor patients .. HOMOVANILLIC ACID (HVA) AND VANILLYMANDELIC (VMA) HVA and VMA are acidic metabolites of catecholamine. Their expanded discharge is seen in patients with neural peak tumors. Assurance of VMA and HVA additionally helps in recognizing what's more, observing treatment in patients of Pheochromocytoma. Their estimations are additionally pertinent for neuroblastomas HYDROXY INDOLE ACETIC ACID (5-HIAA) 9 Urinary HIAA estimation is utilized clinically and aides in determination of indole discharging tumors. Its focus too expanded in patients with carcinoid tumors. HIAA is routinely utilized for observing adequacy of carcinoid condition treatment. INTERLEUKIN-2 RECEPTOR/TAC ANTIGEN (IL-2R) IL-2 α developed receptor, a 55 KD glycosylated protein is finished communicated in certain sorts of lymphoid malignancies. Serum levels of IL-2 are raised in grown-up T-cell leukemia and the marker additionally helps in checking treatment in these patients. LIPID-ASSOCIATED SIALIC ACID IN PLASMA (LASA-P) Expanded centralization of LASA-P is accounted for in numerous malignancies, for example,
  • 7. bosom, gastrointestinal tract, lung, leukemia, lymphoma, Hodgkin's sicknesses and melanoma. The slight increment of this marker is additionally seen in a few provocative maladies demonstrating its poor particularity. The affectability of this marker shifts from 77% to 97% for various tumors. TUMOR SUPPRESSOR GENE P53 P53, a 53 KD atomic phosphoprotein works as tumor silencer by hindering cell multiplication. P53 plays a predominant job in cell apoptosis. P53 quality changes are accounted for in roughly half of a wide range of tumors. Regularly happening P53 quality changes are accounted for in essential bosom, colon, ovarian, lung, and esophageal carcinomas. SQUAMOUS CELL CARCINOMA (SCC) ANTIGEN 10 SCC antigen, a 48 KD protein, is filtered from uterine cervix The antigen fixation is raised or in squamous cell carcinomas of head and neck, lung, throat and butt-centric channel. The most elevated grouping of SCC antigen is found in patients with metastases. The marker rise is additionally seen in 70% patients with cutting edge cervical malignancies. Sequential serum SCC antigen assurance helps in deciding movement furthermore, relapse of cervical malignant growth following chemotherapy. The antigen levels are likewise brought up in certain patients of broad liver ailment. The joined utilization of CEA, NSE and SCC antigen has helped in expanding affectability for location and observing of lung tumors . MONOCLONAL IMMUNOGLOBULIN/PARAPROTEIN Monoclonal immunoglobulin content is of extraordinary incentive in determination just as for observing adequacy of remedial the executives of plasma cell neoplasms specifically numerous Myeloma, Waldenstrom's macroglobulinemia, plasmacytoma, B cell leukaemias and lymphomas(100-104). Ongoing distribution by Yilmaz and his group from Turkey have underscored the requirement for reasonable utilization of tumor markers following the act of proof based medication. It is unnecessary to express that inspite of non-explicitness of wide range of tumor markers accessible today, their potential job in checking whole malignant growth helpful course is exceptionally significant clinically. conclusion: Inspite of these impediments, numerous tumor markers have indicated incredible clinical significance in checking adequacy of various methods of treatments during whole course of sickness in malignant growth patients. Moreover, assurance of markers additionally helps in early discovery of malignant growth repeat and in anticipation.
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