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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

TUMOR MARKERS

Dr. Ismet M. NurSp.PA (K), MM.

Dept. of Pathology Anatomy UNPAD/ HasanSadikin Hospital

Bandung

tumor markers are
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
tumor markers3
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
how to detect
How to detect ?
  • The tissue samples are available from :
    • - exision or biopsy
    • - needle biopsy
    • - cytologic smears

Diagnosis of cancer

methods
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
immuno
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

methods7
Methods

Molecular Diagnosis by

  • Cytogenetic analysis
  • Polymerase Chain Reaction (PCR)
  • Fluorescence Insitu Hybridization (FISH)
  • Flow Cytometry
the techniques can be applied for
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
incidence of breast cancer
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
risk factors
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.
can breast cancer be found early
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
how is breast cancer diagnosed
How Is Breast Cancer Diagnosed?
  • Signs and Symptoms
  • Medical History and Physical Examination
  • Imaging Test for Breast Disease Diagnosis
  • Nipple Discharge Examination
  • Biopsy
laboratory testing of breast cancer biopsy samples
Laboratory Testing of Breast Cancer Biopsy Samples
  • Types of breast cancer
  • Grades of breast cancer
  • Prognostic factors

immunohistochemistry

immunohistochemistry
IMMUNOHISTOCHEMISTRY
  • immunohistochemistry is a staining technique for identifying cellular or tissue constituents (antigens) by using spesific antibody.
ihc for breast cancer
IHC for Breast Cancer
  • Steroid Hormone Receptors
  • HER-2/ neu / c-erbB-2
  • p53
  • bcl-2
  • nm23H1
  • Ki-67 /MIB
  • MUC1
steroid hormone receptors estrogen receptor progesteron receptor er pr
Steroid Hormone ReceptorsEstrogen Receptor/Progesteron ReceptorER/PR
  • Predict the response rate to endocrine therapy
  • Positive hormone receptor status is a favorable prognosis.
slide18

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%

oncogene c erbb 2 neu her 2
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
slide22
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.
slide23
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.
bcl 2
Bcl-2
  • bcl-2 is a suppressor of apoptotic cell death.
  • The expression of bcl-2 is correlated positively with higher estrogen receptor content.
ki 67 mib 1
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.
conclusions
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.