Correlation of c-erbB-2 (HER-2/neu) expression and amplification with other prognostic factors in breast carcinoma

ABSTRACT CORRELATION OF c-erbB-2 (HER-2/neu) EXPRESSION AND AMPLIFICATION WITH OTHER PROGNOSTIC FACTORS IN BREAST CARCINOMA Several factors have been identified in breast carcinoma which affect the biologic behavior, therapy and the prognosis of the tumor. Among these, c-erbB-2 ( HER-2/neu) oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the Epidermal Growth Factor receptor. In the literature, studies regarding the prognostic role of c- erbB-2 oncoprotein overexpression and gene amplification with and without other parameters is controversial. Immunohistochemistry, PCR, Southern Blot, Northern Blot, Western Blot analyses, ELISA and FISH are the methods of detecting c-erbB-2 abnormalities. In this study, paraffin sections from 60 female breast samples were analyzed. Immunohistochemistry was used to detect estrogen status and c-erbB-2 protein expression whereas differential PCR was used to detect c-erbB-2 gene amplification. Differential PCR is an alternative semi-quantitative method for evaluating gene amplification and can be performed in formalin-fixed paraffin-embedded specimens. We compared the prognostic impact of c-erbB-2 gene amplification and protein overexpression with conventional prognostic factors (age, histologic type and size of the tumor, grade, lymphatic invasion, lymph node involvement and estrogen status). In our study, a highly significant degree of concordance (p=0.000) between c-erbB-2 amplification and overexpression was observed. Our results also showed that c-erbB-2 expression and gene amplification in breast carcinoma is significantly related to the number of metastatic lymph nodes (p=0.003), poor histologic grade (p=0.000) and lymphatic invasion (p=0.003). Age, histologic type, tumor size and estrogen status did not correlate with c-erbB-2 status in our study. Our study confirmed the importance of c-erbB-2 overexpression and gene amplification as a single and combined prognostic parameter together with conventional factors and can be detected by both immunohistochemistry and differential PCR techniques. Differential PCR technique provides semi-quantitative, reliable results and can be use routinely. Key words: c-erbB-2,, immunohistochemistry, breast carcinoma, PCR, prognostic factors vn