[Her-2 amplification and p185 expression in invasive breast cancer cells in women]

Abstract

Introduction: The objective of the investigation was to describe p185 protein expression using immunohistochemistry (IHC) and HER-2 gene amplification by fluorescence in situ hybridization (FISH), assessment being semi-quantitative and with the more precise computer image analysis, and to determine whether p185 overexpression is associated with some clinical and morphological parameters such as histological type, histological grade, axillary lymph node status, tumor size, estrogen receptor expression, proliferative index, and age in females with invasive breast carcinoma.

Material and methods: Histological preparations from 390 breast carcinomas were studied with the IHC reaction (HercepTest) based on a polyclonal anti-p185 antibody. HercepTest results classified semi-quantitatively as 2+ and 3+ were evaluated using a computer image analyzer and the p185 index was calculated. HER-2 amplification was carried out with FISH using a unique probe (HER-2) with a satellite probe (CEP17). The FISH reaction was assessed routinely by counting red fluorescence signals emitted by the HER-2 gene and additionally with AnalySIS software (AS). The latter method showed that the mean HER-2 amplification index in carcinomas determined as 2+ was significantly lower as compared to carcinomas defined as 3+ (p < 0.0001). On the other hand, the mean amplification indices of carcinomas classified as 3+ and of 2+ cancers which manifested HER-2 amplification did not differ significantly. High HER-2 amplification values (HER-2/CEP17 > 5) were noted in a similar percentage of carcinomas classified by IHC as 2+ (45.5%) or 3+ (55.5%). No correlation was observed between the intensity of the immunohistochemical reaction to p185 as assessed by computer image analysis and the HER-2 amplification index either in breast carcinomas classified semi-quantitatively as 2+ or 3+. The p185 index in 2+ carcinomas without HER-2 amplification might be higher than in some cancers with HER-2 amplification or even higher than in some carcinomas with HER-2 amplification belonging to the 3+ class. Significant differences were noted in p185 expression between ductal and lobular carcinomas (p = 0.0001) and between lobular and medullar carcinomas (p = 0.003). Invasive ductal carcinomas revealed significant differences in p185 expression depending on histological grade (I degree vs III degree p = 0.02; II degree vs III degree p = 0.02), estrogen receptor expression (p = 0.01), and proliferative index (p = 0.02).