20 4-13grading & staging tumour markers


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20 4-13grading & staging tumour markers

  2. 2. • Prognosis of the course of the disease• Determination of efficacy of various forms of cancertreatment require a high degree of similarity amongthe tumors being considered.
  3. 3. • Systems in semiquantitative terms,• The level of differentiation, or grade• Extent of spread of a cancer within the patient,or stage,
  4. 4. Grading of a cancer is based• Degree of differentiation of the tumor cells and thenumber of mitoses within the tumor as presumedcorrelates of the neoplasms aggressiveness.
  5. 5. • Grades I to IV with increasing anaplasia.• Criteria for the individual grades vary witheach form of neoplasia,• To judge the extent to which the tumor cellsresemble or fail to resemble their normalcounterparts.
  6. 6. • The correlation between histologic appearance andbiologic behavior is less than perfect.• Characterize a particular neoplasm in descriptiveterms,• Well-differentiated, mucin-secreting adenocarcinomaof the stomach, or• Highly undifferentiated, retroperitoneal malignanttumor-probably sarcoma.
  7. 7. Cytologic grading of squamous cell carcinoma of the lung.A. Well-differentiated (grade 1) squamous cell carcinoma
  8. 8. Poorly differentiated (grade 3) squamous cellcarcinoma. The malignant cells are difficult to identifyas being of squamous origin.
  9. 9. • Grading of cancers has proved of less clinicalvalue than has staging
  10. 10. The staging of cancers• Based on the size of the primary lesion,• Its extent of spread to regional lymph nodes,• Presence or absence of blood-bornemetastases
  11. 11. • Great importance in the selection of the bestform of therapy• Staging has proved to be of greater clinicalvalue than grading
  12. 12. • Union Internationale Contre Cancer (UICC)• American Joint Committee (AJC) on CancerStaging.
  13. 13. The UICC employs a classification calledthe TNM system-• T for primary tumor,• N for regional lymph node involvement• M for metastases.
  14. 14. The TNM staging varies for each specific formof cancer, but there are general principles• With increasing size, the primary lesion ischaracterized as T1 to T4.• T0 is added to indicate an in situ lesion. .
  15. 15. • N0 would mean no nodal involvement,whereas N1 to N3 would denote involvement ofan increasing number and range of nodes
  16. 16. • M0 no distant metastases,• M1 or sometimes M2
  17. 17. AJC divides all cancers into stages 0 to IV• Incorporating within each of these stages thesize of the primary lesion , presence of nodalspread & distant metastases.
  18. 18. • Stage 0. DCIS or LCIS (5-year survival rate: 92%).• Stage I.Invasive carcinoma 2 cm or less in diameter(including carcinoma in situ with microinvasion)without nodal involvement (5-year survival rate:87%).
  19. 19. Stage II• Invasive carcinoma 5 cm or less in diameterwith up to three involved axillary nodes or• Invasive carcinoma greater than 5 cm withoutnodal involvement (5-year survival rate: 75%).
  20. 20. Stage III• Invasive carcinoma 5 cm or less in diameter with fouror more involved axillary nodes;• Invasive carcinoma greater than 5 cm in diameterwith nodal involvement;• Invasive carcinoma with 10 or more involvedaxillary nodes;• Invasive carcinoma with involvement of theipsilateral internal mammary lymph nodes; or• Invasive carcinoma with skin involvement (edema,ulceration, or satellite skin nodules), chest wallfixation, or clinical inflammatory carcinoma (5-yearsurvival rate: 46%).
  21. 21. • Stage IV. Any breast cancer with distantmetastases (5-year survival rate: 13%).
  22. 22. Tumor Markers
  23. 23. Tumor MarkersBiochemical indicators of the presence of a tumor.• A molecule that can be detectedin plasma or other body fluids• Tumor markers cannot beprimary diagnosic modalities• Utility to support the diagnosis.• Response to therapy• Indicating relapse during thefollow-up period.•Cell-surfaceantigens,•Cytoplasmicproteins,•Enzymes,•Hormones.
  24. 24. CEA A complex glycoproteinElevations in many benigndisorders• Alcoholic cirrhosis,• Hepatitis,• Ulcerative colitis,• Crohn disease•60% to 90% ofcolorectal,•50% to 80% ofpancreatic•25% to 50% of gastricand breast carcinomasNormally produced in embryonictissue of the gut, pancreas, and liver
  25. 25. Lack both specificity and the sensitivity requiredfor the detection of early cancers• Preoperative CEA levels body burden of tumor.• Elevated CEA levels 6 weeks after therapy indicatesresidual disease.• A rising CEA level indicates recurrence, with anincrease in tumor marker level often precedingclinically detectable disease.• Serum CEA is also useful in monitoring the treatmentof metastatic breast cancer.
  26. 26. AFP Glycoprotein• Useful indicator of hepatocellularcarcinomas and germ cell tumors of thetestis.• Decline rapidly after surgical resectionof liver cell cancer or treatment of germcell tumors.• Less regularly in carcinomas of thecolon, lung, and pancreasEarly in Fetal Life,Yolk Sac,Fetal Liver & Fetal GitAdults withcancerarisingprincipallyinLiverGerm cellsof the testis.
  27. 27. Markers Associated CancersHormonesHuman chorionicgonadotropinTrophoblastic tumors,nonseminomatoustesticular tumorsCalcitonin Medullary carcinoma ofthyroidCatecholamine PheochromocytomaEctopic hormones Paraneoplastic Syndromes
  28. 28. Oncofetal Antigensα-Fetoprotein Liver cell cancer,nonseminomatous germcell tumors of testisCarcinoembryonicantigenCarcinomas of the colon,pancreas, lung, stomach,IsoenzymesProstatic acidphosphataseProstate cancerNeuron-specific enolase Small cell cancer of lung,neuroblastoma
  29. 29. Specific ProteinsImmunoglobulins Multiple myeloma and othergammopathiesProstate-specific antigen andprostate-specific membraneantigenProstate cancerMucins and Other GlycoproteinsCA-125 Ovarian cancerCA-19-9 Colon cancer, pancreatic cancerCA-15-3 Breast cancer
  30. 30. New Molecular Markersp53, APC, RAS mutations instool and serumColon cancerp53 and RAS mutations instool and serumPancreatic cancerp53 and RAS mutations insputum and serumLung cancerp53 mutations in urine Bladder cancer
  31. 31. Serologic Diagnosis• Theoretically, it may be possible to diagnose cancerby detecting cancer cell products in the serum,whether these are molecules secreted by malignantcells or antigens released by periodic death of suchcells.• No general serologic screening methods exist forcancer, but several tests are of value for certaintumors
  32. 32. Radiologic Diagnosis• CT & (MRI) scans, are invaluable for localizingmasses as part of the primary diagnosis or for stagingtumors.• As a general rule, radiologic findings suggestive ofcancer must be confirmed by either cytologic orhistologic examination of biopsy material beforetreatment can be started.