Tumor markers are substances produced by tumor cells or the body's response to tumors that can be detected in blood, urine, or tissue. They are used to screen for cancers, help diagnose cancer, determine prognosis, detect recurrence, and monitor treatment response. An ideal tumor marker would be highly sensitive and specific to a particular cancer, correlate with tumor size, respond rapidly to treatment, and predict recurrence before clinical detection. Examples of commonly used tumor markers include AFP, CEA, CA125, PSA, and CA15-3. Their levels can be elevated in both cancer and some benign conditions.

1. TUMOUR MARKERS
Dr. Ajit Kumar Singh
PGT-Laboratory medicine
CNCI , Kolkata-700160
Moderator
Dr. Garima Chauhan
MD (Biochemistry)
Assistant Professor
Department of laboratory medicine
Chittaranjan National Cancer Institute, Kolkata

2. DEFINITION
 Substance that can be detected in higher than normal amount in serum ,
urine, or tissue of patient with certain types of cancer .
 Tumor marker are produced either by the cancer cells themselves or by the
body in a response to the cancer.
 No tumor marker is pathognomonic
 Most used as a surveillance tool to monitor for recurrence of the neoplasm

3. USES OF TUMOUR MARKERS
o Screening populations at risk
Not all tumor markers are good screening tools
o Diagnosis
Use results from markers, imaging, risk factors, and symptoms
o Prognosis
Concentration of the marker determines prognosis
o Detection of recurrence
Once tumor is removed, elevations of marker can indicate regrowth
o Monitoring response to treatment
Decreased levels of tumor marker indicate therapy is working, increased levels of tumor
marker may indicate need for a change to therapy
o Clinical staging of cancer
o Estimating tumor volume (eg . CHOREOCARCINOMA )

4. 1. Detectable only if tumour is present
2. Identifies the type of tumour
3. Circulating concentration correlates with the mass of tumour present
4. Responds rapidly to treatment-induced remission
5. Responds rapidly to relapse (Predict recurrences before they are
clinically detectable)
6. Should predict outcome
7. In patients with stable disease
8. Test should be cost effective
What are the characteristics of an ideal tumor marker?

5. Classification according to type of the molecule:-
1 .Enzymes or isoenzymes (ALP,LDH, PAP)
2 .Hormones (calcitonin, β-Hcg)
3 .Oncofetal antigens (AFP, CEA)
4.Carbohydrate epitopes recognised by monoclonal antibodies
(CA 15-3,CA 19- 9,CA125)
5.Receptors (Estrogen, progesterone)
6.Protein Markers (Paraproteins)

6. DETECTION OF TUMOUR MARKER
Serological:
Enzyme assays.
Immunological:
CLIA.
ELISA.
Cytogenetic analysis:
FISH.
Spectral karyotyping(SKY).
Comparative genomic hybridization
(CGH).
Genetic analysis:
Sequencing.
Reverse transcription.
Electrophoresis.
DNA micro-array analysis.
Proteomics:
Surface-enhanced laser desorption/ionization

7. Chemiluminescent immunoassay (CLIA)

9. Examples of some clinically important tumor
markers
1. AFP (alpha fetoprotein):
 Alpha fetoprotein is protein that is produced in early fetal life.
 AFP is the major serum protein of human fetus, and it falls to low levels by one
year of age.
 The cut-off value ofAFP is 0-9 U/ml, but it reaches 500 U/ml in late pregnancy.
 However, elevated levels (more than 500 U/ml) are found in many cases of 10HCC,
Hepatoblastoma (Fibrolamellar Variant – Neurotensin ) and GCT.
 Prognosis -GCT
• Furthermore AFP may also be increased in serum of non-neoplastic conditions. In these
cases the rise may be transient, and associated with the tissue (usually the liver) response
to injury, and usually of lesser magnitude (100-300 U/ml )

10. 2. CEA ( Carcinoembryonic Antigen )
 Itisaglycoprotein moleculenormallyfoundin thetissueofa developing fetus.
 Levels of CEAin the blood decrease after birth.
 CEAis normally found in small amounts in the blood of most healthy people.
 Cut-off value of CEAis about 0- 3 ng/ml.
 High CEA levels (above 5 ng/ml) have been found in colorectal adenocarcinoma and in
some tumors of the lung, pancreas, uterus, and breast.
 Less marked elevations occurs in non-neoplastic diseases such as emphysema,
ulcerativecolitis,pancreatitisandalcoholism,andinserumofheavysmokers.
3. CA 15-3 (Cancer antigen 15-3)
 CA15.3 is the most reliable and highly specific tumor marker for breast cancer.
 The CA15.3 level can provide prognostic information in the follow-up management of
patients with breast cancer.
 Cut-off value of CA15-3 is 0-35 units/ml.

11. 4. CA19-9 (Cancer antigen 19-9 )
 Cancer antigen is a protein that is found in very small amounts on the surface of certain
cancer cells.
 Cut-off value is 0-35 units/ml.
 It may be found in the blood when it is shed by tumor cells.
 A CA19-9 test may be done to check: a person’s response to treatment for pancreatic
cancer, especially advanced pancreatic cancer.
 if pancreatic cancer is still growing or has come back (recurred) after treatment
 It is also found in trace amounts in the pancreas, liver, gall bladder and lungs of
healthy adults.
5.CA 125 (cancer antigen 125)
 Cancer antigen 125 is a protein produced by a variety of cells, particularly ovarian cancer
cells.
 CA125 is most reliable and highly specific tumor marker for ovarian cancer.
 Cut-off value is 0-35 units/ml.

12. 6.PSA (prostatic specific antigen)
 It is widely accepted tumor marker in prostaticcancer.
 PSA isglycoproteinproducedonlyby prostatic epithelialcells and it is organ specific.
 Normal level: 0-4ng/ml.
 Elevated Level (more than 4ng/ml) occurs in:
 60% of prostatic cancer.
 40% of benign prostatic hypertrophy.
7.Prostatic acid phosphatase(PAP)
 One of the famous enzymes used as tumor marker.
 The serum level of prostatic acid phosphatase (PAP) is elevated in prostatic carcinoma.
 Certain precautions must be taken before taking serum samples for prostatic acid phosphatase
assay.
 These include avoidance of rectal examination(DRE), and passage of catheter at least 7 days
before sampling and constipation must be avoided.
 As these factors may result in false positive rise in serum acid phosphatsseactivity due to
squeezing of the prostatic tissues.
 Cut-off value is 0.5-11 units/liter

13. 8.LDH (Lactate dehydrogenase)
 An elevationin all five LDH isoenzymes (LDH1, LDH2, LDH3, LDH4, LDH5) canbe
seenin leukemia and lymphoma.
 Selective increases in LDH isoenzymes LDH3 and LDH5 (liver enzyme) may
occur in liver carcinoma.
 Cut-off value of total LDH ranges from 140 to 240units/liter.
9. Calcitonin
 Patients with medullarythyroid carcinomacan be screenedby measuring
calcitonin levels.
10. HCG (Human chorionic gonadotropin)
 Hormone produced by placenta, and used for detection of pregnancy.
 Reaching maximum level at 8th week of gestation.
 It increases in testicular carcinoma , GCT, GTN .

14. Human Chorionic Gonadotropin (βhCG)
 Multiple forms in serum (intact heterodimer, free alpha, free
beta chains, various degradation products)
 Function is to maintain progesterone production during first
2 weeks of pregnancy
Reference: <5 U/L
Elevated βhCG:
 Physiological condition: pregnancy
 Benign condition: pituitary adenoma
 Malignancies:
 Gestational trophoblastic disease
 NSGCT
 SGCT testis (20%)

15. 12. Cancer antigen CA 27-29
 Ca 27-29 levels can be elevated in breast as well as in cancers of the colon, stomach, kidney, lung,
ovary, pancreas, uterus, and liver
 First trimester pregnancy ,endometriosis, benign breast disease, kidney disease, and liver disease
also may be associated with elevated CA 27-29 levels.
13. P53
 Tumor suppressor gene.
 Because of its central role in preventing the propagation of cells with DNA damage, P53 has been
referred to as the “guardian of the genome”.
 The P53 gene on chromosome 17p is the most commonly mutated gene in human cancer.
 In about 50 to 70 percent of CRCs, P53 inactivation occurs by a mutation of one allele followed by
loss of the remaining wild type gene (Knudson’s 2 hit hypothesis).
 In many but not all studies, patients whose tumors harbor P53 mutations have worse outcomes and
shorter survival than those without such mutations.

16. • It is unclear why patients with the Li Fraumeni syndrome (a condition caused by a
germline mutation in p53 in which patients frequently develop carcinomas,
sarcomas, and leukemias) are not at particularly increased risk of developing
CRCs.
• Li-Fraumeni syndrome (LFS) : is an inherited autosomal dominant disorder that is
manifested by a wide range of malignancies that appear at an unusually early age.
• Li-Fraumeni syndrome is also known as the Sarcoma, Breast, Leukemia, and
Adrenal Gland (SBLA) cancer syndrome.
• This cancer predisposition syndrome is inherited as an autosomal dominant
disorder and is associated with abnormalities in the tumor protein P53 gene (TP53).

17. PROTEIN MARKERS
1.Ferritin- Ferritin is a marker for Hodgkin lymphoma, leukemia, liver, lung and breast cancer.
2.Thyroglobulin- It is a useful marker for detection of differentiated thyroid cancer
(Follicular & papillary).
3.Paraproteins(M-protein Immunoglobulin- Bence-Jones protein) - is a free monoclonal
immunoglobulin light chain in the urine it is a reliable marker for multiple myeloma
4.β2 microglobulin

18. RECEPTOR MARKERS
1.Estrogen receptors
2.Progesterone receptors
3.HER2 or c-erb2
4.BRAF
5.ALK
6.KRAS

19. ENZYMES
 Alkaline Phosphatase (ALP)-
 LDH
Biological reference interval
Physiological variation
Pathological variation
Type

20. Biogenic amines
• Pheochromocytoma are diagnosed by testing 24-hour urine
samples for catecholamines and their metabolites as well as by
determinig plasma metanephrine levels.
• The 24-hour urinary vanillylmandelic acid (VMA) excretion has
poor diagnostic sensitivity and specificity compared with
fractionated 24-hour urinary metanephrines.
• False-positive VMA tests may result from ingestion of caffeine,
raw fruits, or medications (alpha-methyldopa).
• Urinary metanephrine are 98% sensitive and also about 98%
specific for pheochromocytomas, whereas VMA measurement
are slightly less sensitive and specific

21. Other common tumour markers
Neuron specific enolase – neuroendocrine tumours like small cell
carcinoma of lung, neuroblastoma, pheochromocytoma etc.
Chromogranin A
Inhibin
SCCA
S-100
HMB-45
Melan-A
Mitf-1
Vimentin

23. New tumor marker
 Oncotype-DX
 PAX-8
 TTF
 NMPs
 BTAs

24. Some benign conditions associated with rise in
tumor markers
Associated non-malignant conditions
Viral Hepatitis, liver injury, pregnancy
Testicular failure, pregnancy
Smokers, hepatitis, cirrhosis, pancreatitis, gastritis
• Marker
• AFP
• β-hCG
• CEA
• PSA Prostatitis, benign prostatic hyper-plasia

27. • Specificity
• It is a measure of the incidence of negative results in persons known to be free of a disease, that is true negative (TN).
• Specificity = TN/ All without disease (FP +TN) X 100
• Efficiency
• The efficiency of a test is the number of correct results divided by the total number of tests.
• Efficiency = TP + TN/ Total number of tests (TP + TN + FP + FN) X 100
• Sensitivity
• It is a measure of the incidence of positive results in patients known to have a condition, that is true positive (TP)
• Sensitivity = TP/ All with disease (TP +FN) X 100
• Predictive values
• The predictive value of a test is a measure (%) of the times that the value (positive or negative) is the true value, i.e. the percent
of all positive tests that are true positives is the Positive Predictive Value (PV +ve).
• PV +ve = TP/ All positive (TP +FP) X 100
• PV -ve = TN/ All negative (TN +FN) X 100

28. Conclusions
Tumor markers have changed the diagnosis and management of patients with
malignancies
They play a vital role in staging testicular cancers, screening for prostate cancers,
prognosis in colorectal cancers.
They are being evaluated in screening for HCC, epithelial ovarian cancers.
Further research is needed to refine the role of these markers in management of
cancer patients.
Recent advances in technology provide additional malignant tumor markers in the
immediate future

29. 1. Have high disease sensitivity i.e.it should be positive in all patients with particular cancer.
 Sensitivity of any tumor marker refers to the number of true positives, and it could be calculated as
follows:
• Number of true positives
X 100
• Number of true positives + False negatives
 True positive isa malignant case which gives an elevated marker level above the
cut- off value.
 False negative is a malignant case which gives a normal value for the marker
where as it is proved malignant histopathologically.
 Cut-off value is the highest value obtained by the normal control.
2. Have high disease specificity i.e. it should be negative in all normal
population.
 Specificity of any tumor marker refers to the number of true negatives (normal
individuals), and it could be calculated as follows:
• Number of true negatives
X 100
• Number of true negatives + False positives
True negative is a normal case which gives a normal value for the marker.
False positive is a normal case with elevated marker level abovethe cut-off value.

30. IDEAL TUMOR MARKERS
• Be specific to the tumor
• Level should change in response to tumor size
• An abnormal level should be obtained in the presence of
micrometastases
• The level should not have large fluctuations that are
independent of changes in tumor size
• Levels in healthy individuals are at much lower
concentrations than those found in cancer patients
• Predict recurrences before they are clinically detectable
• Test should be cost effective

31. Carcinoembryonic antigen (CEA)
• CEA is a highly glycosylated cell surface glycoprotein involved in intercellular
adhesion
• CEA is shed from the cell surface into the circulation and can be detected in
serum.
•It is thought that infiltrating tumour growth breaks down the normal
barriers that usually prevent CEA from entering the circulation.
Malignancies associated with
elevated CEA levels
Over-expressed primarily by
adenocarcinomas:
 Colon
 Rectum
 Breast
 Lung
Benign conditions associated with
elevated CEA levels
 Pulmonary emphysema
 Bronchitis
 Acute ulcerative colitis
 Rectal polyps
 Hepatitis
 Alcoholic cirrhosis
 Obstructive jaundice
 Smokers
 Renal disease

32. CEA
 Normal range: <5ng/ml
 Smokers: <10ng/ml
 Suspect malignancy at >20ng/ml
 Suspect metastatic spread at >50ng/ml
 T1/2: 3 days (1-5 days)
Dukes’ Grade
A
B
C
D
% patients
CEA >5ng/ml
4
26
44
65

33. Cancer Antigen 125 (CA125)
 Glycoprotein, with unknown biological function
 Marker developed through immunization of mice with cells from an
ovarian carcinoma line, to produce the OC 125 monoclonal antibody
Epithelial cells
• Fallopian tubes
• Endometrium
• Endocervix
• Normal ovary
Mesothelial cells
• Pleura
• Pericardium
• Peritoneum

34. CA125
‘Normal’ serum concentration: <35 kU/L
Elevated in menstruation
T1/2: 5 days (1-5 days)
Malignancies associated with elevated CA 125
80-85% ovarian serous adenocarcinomas
50% Stage I
>90% Stage II
Endometrium
Breast
Uterus
Liver
Stomach
Pancreas
Cervix
Fallopian tubes
Biliary tract
Colon
Lung

37. CA19-9
Normal serum concentration <37 U/ml
T1/2 : 24 hrs
20% patients
with pancreatic
adenocarcinoma
do not produce
CA19-9

39. Prostatic Specific Antigen
(PSA)
 Serine protease
 Liquefy seminal coagulum
 Production is androgen-dependent
 Produced almost exclusively by epithelial component
of prostate gland
 Raised in:
Benign prostatic hypertrophy
Acute and chronic prostatitis
Urinary retention
 T½ = 2.5 days (radical prostatectomy)

40. Carcinoembryonic antigen (CEA)
• Glycoprotein
• Found in embryonic endodermal epithelium
• Serum levels disappear almost completely after birth, but
small amounts may be present in the colon.
• Elevated in primary colorectal cancer as well as with breast,
thyroid, lung, ovarian, prostate, liver, pancreatic cancer.
• Elevated in benign conditions including diverticulitis,
cholecystitis, Pancreatitis, Inflammatory bowel disease,
peptic ulcer disease, bronchitis, liver abscess, and alcoholic
cirrhosis, especially in smokers and in elderly persons

41. • Use of CEA level as a screening test for colorectal
cancer is not recommended
• Useful if obtained preoperatively and postoperatively in
patient with CR Ca
• Preoperative elevation indicator of poor prognosis
• The 2007 ASCO clinical practice guidelines state that the
data are insufficient to support the use of CEA to
determine whether to give a patient adjuvant therapy ,
that data stronger for the use of CEA for monitoring for
postoperative recurrence
• CEA measurement is the most cost-effective approach
for detecting metastasis.

42. • In cases in which the patient would be a candidate for
resection of recurrent colorectal cancer or systemic therapy,
the 2006 ASCO guidelines recommend the postoperative CEA
testing be performed every 3 moths in patient with stage two
or three disease for at least 3 years
• CEA is the marker of choice for monitoring metastatic CR Ca
during systemic therapy.
• CEA can be used in conjunction with diagnostic imaging and
history and physical exam for monitoring patient during active
therapy
• In the absence of measurable disease, an increase in CEA
level may be taken to indicate treatment failure.

43. • Individual laboratory assays vary slightly, but the typical
upper limit of normal for CEA in non-smokers is 3.8
micrograms per liter (mcg/L). For smokers, the upper
limit of normal is 5.5 mcg/L

44. In order to use a tumor marker for screening in the presence of cancer in
asymptomatic individuals in general population, the marker should be produced
by tumor cells and not be present in healthy people.
However, most tumor markers are present in normal, benign and cancer tissues
and are not specific enough to be used for screening cancer.

45. Applications in ovarian cancer detection
Early detection of ovarian cancer through the measurement of CA-125,
usually in combination with other modalities (eg, bimanual pelvic
examination, transvaginal ultrasonography), is the most promising
application of this tumor marker, permitting effective triage of patients for
primary surgery.

46. CA 125
1 Approx 90% of ovarian cancers are epithelial carcinomas and contain a
epithelium–related glycoprotein, cancer antigen 125.
2The major forms in serum have molecular weights of 200 kDa to 400 kDa.
3 Marked elevations (>1500 U/mL) are generally seen with ovarian cancer.
4 The ACOG and Society of Gynecologic Oncologists- recommend gyne-onco
referral for women with a pelvic mass suggestive of ovarian cancer and a serum
CA-125 value >35 U/mL in postmenopausal women or >200 U/mL in
premenopausal women.

47. Alpha-Fetoprotien
• glycoprotein that is normally produced during gestation by the fetal liver and
yolk sac.
• Levels decrease soon after birth in healthy adults.
• serum concentration of which is often elevated in patients with HCC. Serum
levels of AFP do not correlate well with other clinical features of HCC such as
size, stage, or prognosis.
• Elevated serum AFP occurs in pregnancy , with tumors of gonadal origin (both
germ cell(ovary or testicle) and non-germ cell) and in a variety of other
malignancies, of which gastric cancer is the most common.
• Elevated serum AFP may also be seen in patients with chronic liver disease
without HCC such as acute or chronic viral hepatitis . AFP may be slightly higher
in patients with cirrhosis due to hepatitis C .
• Benign conditions that can cause elevations of AFP : cirrhosis, hepatic necrosis,
acute hepatitis, chronic active hepatitis, ataxia telangiectasia, wiskott-aldrich
syndrome, neural tube defect, and pregnancy.

48. • The sensitivity of an elevated AFP level for detecting HCC is
60% .
• AFP is considered to be sensitive and specific enough To be
used for screening for HCC in high risk population .
• Current recommendations are to screen healthy hepatitis B
virus carriers with annual or semiannual measurement of AFP
and to screen carriers with cirrhosis of any etiology with twice-
yearly measurement of AFP level and liver ultrasonography.
• AFP efficacy in early diagnosis of HCC is limited
• Larger proportion of patients diagnosed with HCC are now
AFP seronegative due to imaging technology improvement
•

49. • It is generally accepted that serum levels greater than 500 mcg/L
(normal in most laboratories is between 10 and 20 mcg/L) in a high-risk
patient is diagnostic of HCC.However, HCC is often diagnosed at a
lower AFP level in patients undergoing screening.
• Not all tumors secrete AFP, and serum concentrations are normal in up
to 40 percent of small HCCs.
• Furthermore, an elevated AFP may be more likely in patients with HCC
due to viral hepatitis compared with alcoholic liver disease.
• Elevated levels were associated with the presence of stage III or IV
fibrosis, an elevated international normalized ratio, and an elevated
serum aspartate aminotransferase level.
• AFP levels are normal in the majority of patients with fibrolamellar
carcinoma, a variant of HCC.
• Patients with cirrhosis and persistently elevated AFP values have an
increased risk of developing HCC compared with those who have
fluctuating or normal levels.
• Despite the issues inherent in using AFP for the diagnosis of HCC, it
has emerged as an important prognostic marker, especially in patients
undergoing resection and those being considered for liver
transplantation. Patients with AFP levels >1000 mcg/L have an
extremely high risk of recurrent disease following transplantation,
irrespective of the tumor size

50. CA 19-9
• Cancer antigen 19-9 , sialylated Lewis (a) antigen
• Tumor related antigen
• Glycoprotein
• CA 19-9 levels are not a useful tumor marker.
• CA 19-9 requires the presence of the Lewis blood group antigen (a glycosyl
transferase) to be expressed. Among individuals with a Lewis-negative
phenotype (an estimated 5 to 10 percent of the population), CA 19-9 levels are
not a useful tumor marker
• One study found that serum concentrations above 37 U/mL represented the
most accurate cutoff value for discriminating pancreatic cancer from benign
pancreatic disease, but the sensitivity and specificity for pancreatic cancer at
this level were only 77 and 87 percent, respectively
• The data are insufficient to recommend use CA19-9 for screening, diagnosis,
surveillance, or monitoring of therapy for colon Ca
• 2006 ASCO guidelines there are insufficient data to recommend use of CA 19-9
for screening, diagnosis, or determination of operability of pancreatic cancer

51. • Patient with locally advanced or metastatic cancer
receiving active therapy, CA19-9 can be measured at the
start of therapy and every 1-3 months while therapy is
given, elevation in serial CA19-9 levels may indicate
progressive disease and should be confirmed by
additional studies.
• Although several marker candidates have emerged from
preclinical studies (and one, macrophage inhibitory
cytokine-1, appears particularly promising ), none has
replaced CA 19-9 to date

53. C- KIT
• proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a receptor
tyrosine kinase protein that in humans is encoded by the KIT gene.
• Antibodies to CD117 are widely used in immunohistochemistry to help
distinguish particular types of tumor in histological tissue sections. It is used
primarily in the diagnosis of GISTs, which are positive for CD117, but
negative for markers such as desmin and S-100, which are positive in
smooth muscle and neural tumors, which have a similar appearance. In
GISTs, CD117 staining is typically cytoplasmic, with stronger accentuation
along the cell membranes. CD117 antibodies can also be used in the
diagnosis of mast cell tumors and in distinguishing seminomas from
embryonal carcinomas

54. • around 95 percent of GISTs arising in adults
overexpress KIT.Approximately 80 percent of GISTs
have KIT gene mutations that lead to constitutive
activation of the KIT receptor.

55. PSA
• Androgen-regulated serine protease produced by the
prostate epithelium.
• PSA is normally present in low concentrations in the
blood of all adult males.
• PSA levels may be elevated in the blood of men with
benign prostatic hyperplasia, as well as in men with
prostate cancer
• PSA levels have been shown to be useful in evaluating
the effectiveness of prostate cancer treatment and
monitoring for recurrence after therapy.

57. • In monitoring for recurrence, a trend of increasing levels is
considered more significant than a single absolute elevated
value.
• Although PSA has widely used for prostate Ca screening, the
utility of PSA screening remains controversial.
• In 2010 American cancer society updated its guidelines for the
early detection of prostate Ca to state that men who have at
least a 10 years life expectancy should have an opportunity to
make an informed decision with there health care provider
about whether to be screened for prostate Ca with DRE and
serum PSA, after receiving information about the benefits,
risks, and uncertainties associated with prostate Ca
screening, this recommendation was reinforced in their 2013
guideline.

58. • Studies have estimated that PSA elevations can precede
clinical disease by 5 to 10 years or even longer .
• PSA has a half-life of 2.2 days, and levels elevated by
different benign conditions will have variable recovery
times(DRE, Ejaculation,)
• The five-alpha reductase inhibitors finasteride and
dutasteride lower PSA levels.
• The traditional cutoff for an abnormal PSA level in the
major screening studies has been 4.0 ng/mL .

59. Screening for prostate cancer
• When a decision is made to screen, screening be performed with
prostate specific antigen (PSA) tests at intervals ranging from every
two to four years. We suggest not performing digital rectal examination
as part of screening.
• When a decision is made to screen, screening stop after age 69 or
earlier when comorbidities limit life expectancy to less than 10 years,
or the patient decides against further screening. Stopping screening at
age 65 may be appropriate if the PSA level is less than 1.0 ng/mL.
• Men with an abnormal DRE (if performed) or PSA level above 7 ng/mL
should be referred, without further testing, to an interventional
specialist who can evaluate them for a transrectal ultrasound-guided
prostate biopsy.
• men with a PSA level between 4 ng/mL and 7 ng/mL undergo repeat
testing several weeks later . Prior to repeat PSA testing, men should
abstain from ejaculation and bike riding for at least 48 hours. Men with
symptomatic prostatitis should be treated with antibiotics before
retesting. Men with a repeat PSA level above 4 ng/mL should be
referred for transrectal ultrasound-guided prostate biopsy.

60. • Numerous strategies have been proposed to improve the
diagnostic performance of PSA when levels are less than 10.0
ng/mL. These strategies include measuring PSA velocity
(change in PSA over time), PSA density (PSA per unit volume
of prostate), free PSA, complexed PSA, and using age- and
race-specific reference ranges.
• There is no consensus on using any of the PSA modifications,
and none of them has been shown in clinical trials to reduce
the number of unnecessary biopsies or improve clinical
outcomes. The total PSA cutoff of 4.0 ng/mL has been the
most accepted standard because it balances the tradeoff
between missing important cancers at a curable stage and
avoiding both detection of clinically insignificant disease and
subjecting men to unnecessary prostate biopsies.

61. CA 125
• A protein that is higher than normal in approximately 80 percent of women with ovarian
cancer. It can be measured with a blood test. CA 125 is commonly used to monitor
women with ovarian cancer.
• The normal values for CA 125 may vary slightly among individual
laboratories. In most laboratories, the normal value is less than 35 U
/ml.
• The most common use of the test is the monitoring of people with a known cancer that
elevates CA 125 level, such as cancer of the ovary. In the patient who is known to have a
malignancy, such as ovarian cancer, the CA 125 level can be monitored periodically. A
decreasing level generally indicates that therapy, including chemotherapy, has been
effective, while an increasing level indicates tumor recurrence. Because of normal test
variation, small changes are usually not considered significant. A doubling or halving of the
previous value would be important.

62. • In the patient who is being evaluated for a pelvic mass, a CA
125 level greater than 65 is associated with malignancy in
approximately 90% of cases. However, without a
demonstrable mass, the association is much weaker.
• A number of benign conditions can cause elevations of the CA
125 level, including pregnancy, endometriosis, uterine
fibroids(benign tumors), pancreatitis, normal menstruation,
pelvic inflammatory disease, and liver disease. Benign tumors
or cysts of the ovaries can also cause an abnormal test result.
• Increases can also be seen in cancers other than ovarian
cancer, including malignancies of the uterine tubes,
endometrium, lung, breast, pancreas, and gastrointestinal
tract.

63. • So if you have a higher than normal CA 125 level, you could have
ovarian cancer or a more common and less serious condition. Pelvic
ultrasound may be helpful to know if you have ovarian cancer, although
the only way to know for sure if you have ovarian cancer is to have
surgery. As a result, CA 125 is not recommended as a stand-alone
screening test for ovarian cancer.
• Combined CA 125 and pelvic ultrasound — Several studies have
looked at using CA 125 and pelvic ultrasound together to detect ovarian
cancer. However, the results of these studies have been somewhat
disappointing:
1) Many women had unnecessary surgery because of false positive
test results (the CA 125 or pelvic ultrasound was abnormal but no
cancer was found).
2) Some studies of CA 125 and pelvic ultrasound have found more
cancers at an early, more treatable stage, while others have not. No
published studies have shown that these tests reduce the risk of dying
of ovarian cancer.

64. Cancer antigen CA 27-29
• The MUC-1 gene product in the serum may be
quantitated by using radioimmunoassay with a
monoclonal antibody against the CA27-29
• Ca 27-29 levels can be elevated in breast as well as in
cancers of the colon, stomach, kidney, lung, ovary,
pancreas, uterus, and liver
• First trimester pregnancy ,endometriosis, benign breast
disease, kidney disease, and liver disease also may be
associated with elevated CA 27-29 levels.

65. THANK YOU