Simultaneous Bilateral Breast Carcinomas: A Category with Frequent Coexpression of HER-2 and ER-α, High Ki-67 and bcl-2, and Low p53

Abstract

The aim of this study was to evaluate clinicopathological characteristics and immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and their axillary metastases. Immunohistochemical analysis and in situ hybridization were performed using formalin-fixed/paraffin-embedded tissues. In total, 15 primary and 9 metastatic tumors from 8 patients were evaluated. The expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), Ki 67, p53, bcl-2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was evaluated by chromogenic in situ hybridization (CISH). Four patients were younger that 40 years of age (mean 47 years). Six patients had pleomorphic lobular carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the contralateral breast. One patient had atypical medullary carcinoma in both breasts and 1 patient had atypical medullary carcinoma in 1 breast and pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors and corresponding metastatic tumors was similar for the expression of ER-alpha (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2 and ER-alpha is exceptional in hereditary breast carcinoma and sporadic breast carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression of HER-2 and ER-alpha. P53 protein expression was found in only 2/15 (13%) primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast carcinomas, which often express p53 protein. Most of the patients presented with axillary metastases and had very aggressive course. Characteristically, the tumors showed high levels of expression of ER-alpha and Her2 amplification, were bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical medullary carcinoma there was no expression of ER-alpha or amplification of Her-2.

Immunohistochemically defined subtypes and outcome in occult breast carcinoma with axillary presentation

“…It is noteworthy that the biological features were evaluated on axillary nodes indicating a prognostic role for biological features performed on nodal tissues in OBC. In general, the concordance of the biological features (HER-2 status, ER and PgR expression) between the primary tumour and ipsilateral axillary lymph node metastases is high, ranging from 78 to 90% [23][24][25][26].…”

Chromogenic in situ hybridization compared with other approaches to evaluate HER2/neu status in breast carcinomas

“…For these comparisons, 40 studies with available data 14-18,24,26-30,34-39,41-51,53,55,57-65,68 were analyzed. …”

Pleomorphic lobular carcinoma of the breast: a non-evident diagnosis: case report and reviewof the literature

“…Certains considé -raient que ces deux entité s auraient la mê me origine cellulaire canalaire au dé part et qui, par perte de la diffé renciation des molé cules de cohé sion, entraîneraient la transformation d'un CCI en CLP. Toutefois, des preuves molé culaires ont montré qu'il s'agit de deux entité s distinctes dont le support gé né tique est diffé rent de par la mise en é vidence d'une translocation (1q,16q) objectivé e dans le carcinome lobulaire et le CLP [1,8,18,19]. Le pronostic du CLP est ré servé et dé pend du grade histopronostique, de l'expression des facteurs hormonaux, de la multifocalité et la bilaté -ralité , des lé sions, ainsi que de l'existence d'un envahissement ganglionnaire et viscé ral locoré gional et à distance [3,4,13,[17][18][19]22].…”