A 55-year old woman undergoes surgery for a stage II invasive ductal carcinoma. The mass is removed, with the specimen showing negative margins and no lymph node involvement. To determine treatment options, immunohistochemical studies are performed to evaluate expression of receptors for estrogen, progesterone, and HER2-type EGF. Which of the following markers will most likely show immunoreactivity that is limited to the nucleus?
Estrogen and HER2 receptors
B.
Estrogen and progesterone receptors
C.
Estrogen, HER2, and progesterone receptors
D.
Estrogen receptor only
E.
HER2 receptor only
F.
Progesterone receptor only
The correct answer is B. Breast cancer is the second leading cause of cancer deaths among women. While surgical excision with negative margins and no lymph node involvement has a relatively good prognosis for the patient, an adjunct therapy involving either chemotherapy or radiotherapy is strongly recommended for high-grade cancers. In particular, tumors that express certain receptors such as estrogen, progesterone, and the HER2-type epidermal growth factor (EGF) receptors may make the lesion more susceptible to pharmacologic interventions, including the estrogen receptor antagonist tamoxifen and the HER2 EGF receptor blocker trastuzumab (Herceptin). Since both estrogen (choice D) and progesterone receptors (choice F) are steroid hormone receptors, they will mostly be located in the nucleus to act as transcription factors. These would appear as a nuclear pattern of staining.
In contrast, EGF receptors (choices A, C, and E) are tyrosine kinase receptors and will be largely localized in the cell membrane surface.
MedEssentials (2nd Ed.): pp. 399, 400, 401
First Aid (2008): pp. 450, 451
Estrogen receptor and progesterone receptor are steroid hormone receptors, and therefore are found in the cell nucleus; whereas HER2 receptor (which is in the family of epidermal growth factors) is on the cytoplasmic membrane.
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