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TUMOR MARKERS

TUMOR MARKERS. Dr. Ismet M. Nur Sp.PA (K), MM. Dept. of Pathology Anatomy UNPAD / Hasan Sadikin Hospital Bandung. Tumor markers are :. Biochemical indicators of the presence of a tumor

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TUMOR MARKERS

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  1. TUMOR MARKERS Dr. Ismet M. NurSp.PA (K), MM. Dept. of Pathology Anatomy UNPAD/ HasanSadikin Hospital Bandung

  2. Tumor markers are : • Biochemical indicators of the presence of a tumor • Substances that can often be detected in higher than normal amount in the blood, urine or body tissues of some patients with certain types of cancer • Include cell surface antigens, cytoplasmic proteins, enzymes and hormones

  3. Tumor markers • Produced either by the tumor itself or by the body in response to the presence of cancer. • The utility in clinical medicine is to support the diagnosis, determining in the response to therapy, follow up , and prognosis

  4. How to detect ? • The tissue samples are available from : • - exision or biopsy • - needle biopsy • - cytologic smears Diagnosis of cancer

  5. Methods Immunohistochemistry • Categorization of undifferentiated malignant tumors - keratin for carcinoma ( epithelial origin) - desmin for neoplasm of muscle cell origin • Categorization of leukemia and lymphoma • Determination of site of origin of metastatic cancer

  6. Immuno… • Detection of molecules that have prognostic or therapeutic significance - breast cancer : ER, PR, c-erbB2, p53 BRCA1/ BRCA2 - ovarian cancer / endometrial cancer : ER, PR, c-erbB2, BRCA1/ BRCA2

  7. Methods Molecular Diagnosis by • Cytogenetic analysis • Polymerase Chain Reaction (PCR) • Fluorescence Insitu Hybridization (FISH) • Flow Cytometry

  8. The techniques can be applied for • Diagnosis of malignant neoplasm • Prognosis of malignant neoplasm • Detection of minimal residual disease • Diagnosis of hereditary predisposition to cancer

  9. Selected tumor markers

  10. Incidence of breast cancer : • Rare before age 20, rises steadily around the age of menopause • In USA and Canada 1 in 8 women will develop breast cancer. • In Indonesia , second cause of mortality in women after cervix cancer

  11. Risk factors • Maternal relative with breast cancer • BRCA1 and BRCA2 genes. • Longer reproductive span. • Obesity • Nulliparity • Later age at first pregnancy. • Atypical epithelial hyperplasia • Previous breast ca.

  12. Can Breast Cancer Be Found Early ? • In USA screening mammogram every year for women aged 40 and older. • Between aged 20-39 , clinical breast examination by a health professional every 3 years. • Women aged 20 or older BSE every month

  13. How Is Breast Cancer Diagnosed? • Signs and Symptoms • Medical History and Physical Examination • Imaging Test for Breast Disease Diagnosis • Nipple Discharge Examination • Biopsy

  14. Laboratory Testing of Breast Cancer Biopsy Samples • Types of breast cancer • Grades of breast cancer • Prognostic factors immunohistochemistry

  15. IMMUNOHISTOCHEMISTRY • immunohistochemistry is a staining technique for identifying cellular or tissue constituents (antigens) by using spesific antibody.

  16. IHC for Breast Cancer • Steroid Hormone Receptors • HER-2/ neu / c-erbB-2 • p53 • bcl-2 • nm23H1 • Ki-67 /MIB • MUC1

  17. Steroid Hormone ReceptorsEstrogen Receptor/Progesteron ReceptorER/PR • Predict the response rate to endocrine therapy • Positive hormone receptor status is a favorable prognosis.

  18. The predictive power of combined ER/PR phenotypes in patients with advanced/metastatic breast cancer receiving endocrine therapy (American Univ of Beirut) :Phenotype Incidence Response rateER+/PR+ 58% 77%ER+/PR- 23% 27%ER-/PR+ 4% 46%ER-/PR- 15% 11%

  19. IHC staining of ER :

  20. Oncogene : c-ErbB-2/neu/HER-2 • neu/HER-2 oncogene encodes a 185 kDa transmembrane glycoprotein. • The neu/HER-2 gene product possesses tyrosine kinase activity. • Overexpression in about 30% Ca. Related to resistance chemoth/ , grow and spread more agressively • Treated with HERCEPTIN

  21. IHC of C-ErbB-2/neu/HER-2:

  22. p53 • P53 is tumor suppressor gene which can induce apoptosis after irreparable cell damage and regulates the normal cell growth cycles by activating the transcription of involved gene. • Inactivation or mutation of p53 leads to replication of damaged DNA thus promoting the development of malignant cell clones.

  23. Overexpression of mutant p53 can be detected by IHC. • Overexpression of p53 seems to be related to resistance against certain regimens of endocrine and cytostatic chemotherapy.

  24. IHC of p53

  25. Bcl-2 • bcl-2 is a suppressor of apoptotic cell death. • The expression of bcl-2 is correlated positively with higher estrogen receptor content.

  26. IHC of bcl-2

  27. Ki-67 / MIB-1 • Ki-67 is nuclear protein which is expressed in the S,G2 and M phase of dividing cells. • Expression of Ki-67 is used as an index of proliferative activity in breast cancer. • The presence of <10% low rate, 10-20% intermediate and >20% is • high proliferative rate.

  28. IHC of Ki-67

  29. Conclusions : • Immunohistochemistry is a staining technique for detecting many prognostic factors of breast cancer. • The accurate examination and reporting of standard pathologic features remains very important in the diagnosis and prognosis of women with breast cancer.

  30. THANKYOU

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