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1. With regard to biomarkers for breast cancer, which of the following matched pairs is incorrect?

A. Estrogen receptor/Tissue-based biomarker

B. Carcinoembryonic antigen (CEA)/Serum-based biomarker

C. HER2/Serum-based biomarker

D. Progesterone receptor/Tissue-based biomarker

The correct answer is C. HER2, which is also known as ERBB2 and NEU, is a tissue-based marker. HER2 is a transmembrane receptor with cytoplasmic tyrosine kinase activity.

2. Estrogen receptor and progesterone receptor status is routinely assessed by which method in the laboratory?

A. Fluorescent in-situ hybridization (FISH)

B. Immunohistochemistry (IHC)

C. Chromogenic in-situ hybridization (CISH)

D. Periodic acid-Schiff (PAS) staining

The correct answer is B. The IHC method evaluates the percentage of cells with nuclear estrogen and progesterone receptors. A tumor is scored positive for either of the receptors if >1% of the tumor cell nuclei are immunoreactive.

3. One of the following methods is not used to determine HER2 status. Identify the method which is not used to determine HER2 status.

A. Immunohistochemistry (IHC)

B. Chromogenic in-situ hybridization (CISH)

C. Karyotype analysis

D. Fluorescence in-situ hybridization (FISH)

The correct answer is C. FISH assesses HER2 status at the DNA level with a fluorescent-labeled nucleic acid probe that recognizes the HER2 gene. In the CISH method, an alternative to FISH, the HER2 probe is visualized by an immunoperoxidase reaction. Immunohistochemistry assesses HER2 status at the protein level, and the result is presented on a semiquantitative scale with higher numbers representing more HER2 protein expression. There is no role for karyotype analysis in the determination of HER2 status.

4. Which of the following tumor-suppressor gene mutations is found in the largest number of hereditary breast and ovarian cancer cases?

A. TP53 mutation

B. PTEN (phosphatase tensin homolog)

C. BRCA1 and BRCA2

D. STK11

The correct answer is C. All of the choices listed represent highly penetrant forms of hereditary breast cancer. However, the BRCA1 and BRCA2 mutations represent a much larger proportion of hereditary breast cancer cases than the other choices.

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