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Immunohistochemical Expression of c-erbB2, c-erbB3 and c-erbB4 Protein in Breast Cancer

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=Abstract =

Immunohistochemical Expression of c-erbB2, c-erbB3 and c-erbB4 Protein in Breast Cancer

Kyong-Sik Leel, Ja-Yun Koo" Hyun Cheol Chung", Chang-Ok Suh', Hy-De Leel, Byung Chan Leel, Woo-Hee Jung4 and Woo-Ick Yang4

Department of General SurgeryJ, Internal Medicini, Radiation oncologl.

Patho[og/ Yonsei University, College of Medicine, Seoul, Korea

Breast cancer is the third leading cause of cancer related deaths in Korean women. Members of the erhB receptor family, the EGF receptor and c-erbB2, c-erbB3 and c-erbB4. are commonly over-expressed in human breast cancer and there is a high correlation with an aggressive breast cancer phenotype and poor patient prognosis. Since the over~expression of the EGF receptor and c-erbB2 suggested that signalling of erbB receptors may contribute to the development and progression of breast cancer, we investigated the correlation of clinicopathological factors and the immunohistochemical expression of c-erbB2, c-erhB3 and c-erbB4. To detennine the c-erhB immunoreactivity, we used Rabbit anti-human c-erbB2 oncoprotein (DAKO, Denmark), mouse monoclonal c-erbB3(RTJ.2, Santa Cruz) and rabbit polyclonal antibody c-erbB4(Santa Cruz) directed against each c-erbB protein by immunohistochemistry from paraffin-embedded tissue in a series of 190 women with breast cancer. About 25.8%(49 out of 190 patients) of breast cancers overexpressed c-erbB2, and 40.0%(76 out of 190 patients) and 18.9%(36 out of 190 palieuts) overexpressed c-erbB3 and c-erbB4, respectively. Poor histologic grade showed tendency of positive correlation of the positivity of c-erbB2 and 3 but without statistical significance and no correlation with c-erbB4. We observed positive correlations among c-erbB2, c-erhB3 and c-erbB4 expression.(p<0.05) Estrogen receptors (ER) showed inverse correlations with c-erbB2(p=-0.OOl), c-erbB3(p=0.043) and c-erbB4(p-0.197) and progesterone receptors also showed inverse correlation with c-erbB2(p-O.018). Tumor size (p>O.05) and lymph node status(p>O.05) were not related with c-erbB family expression. The expressions of c-erbB2, c-erbB3 and c-erbB4 showed no survival benefit or no disease free benefit compared to c-erhB family negativity in univariate analysis (Kaplan-Meier life table analysis). Our results suggest that c-erbB2, c-erbB3 and c-erbB4 may regulate the growth of breast cancer by the interactions of these family of growth factor receptor that are dependent of honnonal control. (KoreanJ of Breast Cancer 1998;1:215...225) Key Words: c-erbB2, c-erbB3, c-erbB4, Breast cancer

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