Immunohistochemical detection of EGFR, p185^erbB-2, Bcl-2 and p53 in breast carcinomas in pre-menopausal and post-menopausal women

Abstract

Young pre-menopausal women with breast carcinomas have an overall worse prognosis than older, post-menopausal women. Because histologic grade is a major predictor of tumor behavior and correlates with biomarker expression, we assessed the immunohistochemical expression of epidermal growth factor receptor (EGFR), p185(erbB-2) and Bcl-2, and nuclear accumulation of p53 in breast carcinomas in pre- and post-menopausal women with equivalent histologic grades. This allowed identification of differences in biomarker expression and prognostic significance in pre- and post-menopausal women independent of histologic grade. We investigated 100 infiltrating ductal carcinomas (IDC) in pre-menopausal women, ages 45 years and younger, and 100 IDC in post-menopausal women, ages 65 years and older. The IDC were selected so that the proportions of high and low/moderate grade carcinomas were equal in the pre- and post-menopausal groups. Prognostic utility of biomarker expression in pre- and post-menopausal groups was determined by product limit and multivariate analysis of survival. There were statistically significant differences in cytoplasmic expression of EGFR and Bcl-2 and nuclear accumulation of p53, but not in the expression of p185(erbB-2), in carcinomas of high vs. low histologic grade. There was no difference in the expression of EGFR, p185(erbB-2) or Bcl-2, or in nuclear accumulation of p53 in these IDC from pre- vs. post-menopausal women. Bcl-2 and the nuclear accumulation of p53 were of prognostic significance in our overall study population; however, when assessing pre- and post-menopausal women separately, Bcl-2 and p53 were of prognostic significance only in pre-menopausal, but not post-menopausal women. In summary expression of EGFR and Bcl-2 and nuclear accumulation of p53 were significantly associated with histologic grade, but not with menopausal status. In addition, there were differences in the prognostic effectiveness of these biomarkers in pre- vs. post-menopausal women.

Immunohistochemical expression of epidermal growth factor receptor in breast cancer

“…It has been reported in some investigations that EGFR expression could be significantly associated with nuclear grade [14,15]. In the current study, the proportion of nuclear grade 3 tumors was found to be comparatively higher in EGFR-expressing cancers.…”

A Shift from Nuclear to Cytoplasmic Breast Cancer Metastasis Suppressor 1 Expression Is Associated with Highly Proliferative Estrogen Receptor-Negative Breast Cancers

“…The breast cancers constituting the microarrays were also immunostained for detection of expression of ER, PR, ErbB2, p53, Bcl2, p27 Kip1 and Ki-67, as previously described [31, 32]. Each of these protein biomarkers functions in the growth and progression of breast cancer and is a prognostic indicator or is associated with other indicators of prognosis.…”

“…Expression of ErbB2 at the cell membrane and cytoplasmic expression of Bcl2 were semiquantified by the same immunoscoring system used for BRMS1 and as previously described [31]. For ER, PR, p53, Ki-67 and p27 Kip1 , the percentage of cells with nuclear staining was determined.…”

“…Sections were incubated in anti-BRMS1 (S07050, 1: 1,000), and subsequent immunostaining was carried out as described above. Immunostaining for Bcl2, ErbB2, p53, ER, PR, p27 Kip1 and Ki-67 was performed as previously described [31, 32]. Briefly, immunostaining for Bcl2 required antigen retrieval consisting of incubation in boiling 10 mM citrate buffer (pH 6.0) for 5 min.…”

Primary Cilia Are Decreased in Breast Cancer: Analysis of a Collection of Human Breast Cancer Cell Lines and Tissues

“…Formalin-fixed, paraffin-embedded primary breast cancer tissues with corresponding non-cancerous, histologically normal breast tissue from the cancer resection specimens were obtained from the archives of the UAB Department of Pathology after Institutional Review Board approval. The breast cancer tissues were characterized for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu expression by IHC, as described previously (Talley et al 2002(Talley et al ,2008.…”