TUMOR MARKERS

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TUMOR MARKERS

• Dr. Ismet M. Nur Sp.PA (K), MM.
• Dept. of Pathology Anatomy UNPAD/ Hasan Sadikin
  Hospital
• Bandung

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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

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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

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How to detect ?

• The tissue samples are available from
• - exision or biopsy
• - needle biopsy
• - cytologic smears
• Diagnosis of cancer

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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

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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

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Methods

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

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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

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Selected tumor markers
Markers Associated cancer
Hormones HCG ER/ PR Oncofetal Antigens Alpha-fetoprotein CEA Isoenzymes Prostatic acid phosphatase Specific protein Prostate spesific antigens Mucin and other Glycoproteins CA-125 CA-15.3 Trophoblastic tumors Breast and endometrial Ca. Liver Ca Breast, colon, pancreas ca. Prostate cancer Prostate cancer Ovarian cancer Breast cancer
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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

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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.

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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

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How Is Breast Cancer Diagnosed?

• Signs and Symptoms
• Medical History and Physical Examination
• Imaging Test for Breast Disease Diagnosis
• Nipple Discharge Examination
• Biopsy

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Laboratory Testing of Breast Cancer Biopsy
Samples

• Types of breast cancer
• Grades of breast cancer
• Prognostic factors
• immunohistochemistry

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IMMUNOHISTOCHEMISTRY

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

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IHC for Breast Cancer

• Steroid Hormone Receptors
• HER-2/ neu / c-erbB-2
• p53
• bcl-2
• nm23H1
• Ki-67 /MIB
• MUC1

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Steroid Hormone ReceptorsEstrogen
Receptor/Progesteron ReceptorER/PR

• Predict the response rate to endocrine therapy
• Positive hormone receptor status is a favorable
  prognosis.

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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 77ER/PR- 23 27ER-/P
R 4 46ER-/PR- 15 11
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IHC staining of ER
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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

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

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• 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.

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IHC of p53
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Bcl-2

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

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IHC of bcl-2
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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 lt10 low rate, 10-20
  intermediate and gt20 is
• high proliferative rate.

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IHC of Ki-67
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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.

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