Carcinomas from postmenopausal patients generally demonstrated higher levels of ras p21 than those from premenopausal patients, but no significant difference in ras p21 expression in carcinomas between estrogen-receptor rich and estrogen-receptor poor patients was found.
This finding suggests that different causal mechanisms operate for these two types of breast cancer and supports the hypothesis that an early first birth protects against breast cancer by reducing the level of ERs in the mammary epithelial cells from which carcinomas develop.
The diploid tumors were most often estrogen receptor-positive (nine of nine examined carcinomas), whereas 13 of 19 non-diploid tumors studied did not contain estrogen receptors.
A higher percentage of comedo-invasive carcinomas demonstrated aneuploidy 71%; p = 0.0158), elevated levels of S-phase fraction (75%; p = 0.0016) and Ki-67 staining (55%; p = 0.0512), overexpression of HER-2/neu oncogene (47%; p = 0.0011), and were ER negative (35%; p = 0.0148), PR negative (47%; p = 0.0073) when compared to noncomedo-invasive carcinomas.
The expression of mRNAs for epidermal growth factor (EGF), transforming growth factor alpha(TGF alpha), EGFR, platelet-derived growth factor (PDGF) A and B chain, PDGF receptor (PDGFR), transforming growth factor beta (TGF beta), erbB-2 and estrogen receptor (ER) genes was first examined in 6 human esophageal carcinoma cell lines, 6 xenoplanted and 15 surgically resected esophageal carcinomas.
We have used a new technique of polymerase chain reaction select suppression subtractive hybridization to identify genes that are expressed only in ER-negative carcinomas.
We compared our findings with conventional clinicopathological indicators [menopausal status, number of axillary nodes, histological grade, tumor size and type, estrogen receptor (ER), and progesterone receptor] and with p53 protein expression. bcl-2 protein was present in 65% of the carcinomas (117/180) and it was significantly associated with ER and progesterone receptor and inversely associated with p53 in both the groups of patients treated with adjuvant chemotherapy and tamoxifen.
Early immunohistochemical prognostic studies produced equivocal results but we, and others, have recently shown that strong staining for cyclin D1 is more likely to be seen in well differentiated, estrogen receptor positive carcinomas.
These results indicate that Akt3 may contribute to the more aggressive clinical phenotype of the estrogen receptor-negative breast cancers and androgen-insensitive prostate carcinomas.
Although mammary tumor development appears hormone-responsive at early stages, invasive carcinomas are hormone-independent, which corresponds to the loss of estrogen receptor-alpha expression during tumor progression.
We applied comparative genomic hybridization (CGH) to analyze 105 primary breast carcinomas using histograms to indicate the incidence of DNA imbalances of tumor subgroups and difference histograms to compare invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive and -negative tumors (ER(+)/ER(-)).
The histological grade and the expression of estrogen receptor (ER) significantly influenced the prognosis of these NE carcinomas, either pure or NE-apocrine differentiated.
Duodenal carcinomas were methylated more frequently or had increased methylation densities than biliary carcinomas at p14 (P = 0.04), hMLH1 (P = 0.04), MGMT (P = 0.01), MINT1 (P = 0.01), MINT25 (P = 0.01), MINT27 (P = 0.001), RAR beta (P = 0.03), and ER (P = 0.001), and than ampullary carcinomas at RAR beta (P = 0.02) and ER (P = 0.03).
Subsequent comparison between 20 carcinomas using AFM220xe5, with and without LOH in terms of pathological parameters showed significant associations with differences in age (P = 0.04) ER (P = 0.05) Ki-67 (P = 0.04) and PR (P = 0.01) a trend toward significance was found for tumor size (P = 0.06) and histological grade III (P = 0.06).
Regional loss of ER-alpha expression occurs in breast tumors and is consistently present in hypoxic regions defined by the proximity of necrosis and induction of hypoxia-induced genes carbonic anhydrase IX (CA-IX) and glucose transporter 1 (Glut-1), in both in situ (n = 29; P < 0.0001) and invasive (n = 20; P = 0.0001) carcinomas.
The fact that the mutation was not found leads us to believe that this mutation is absent from most cells in invasive carcinomas and furthermore that the major expression product of the ER-alpha gene in cancers does not contain the K303R mutation.
The novel estrogen receptor (ER)-interacting protein and the proline-, glutamic acid-, and leucine-rich protein 1 ( PELP1 ), also called the modulator of nongenomic activity of ER ( MNAR ), have been shown to activate steroid hormone receptors in mammary carcinomas by nongenomic and genomic mechanisms.
The majority of spontaneous and DMBA-induced carcinomas and sarcomas from p53(R270H/+)WAPCre mice is estrogen receptor alpha positive, and expression profiles of genes also implicated in human breast cancer appear similarly altered.