Distribution of estrogen and progesterone receptors isoforms in endometrial cancer

Abstract

Background70–80% of sporadic endometrial carcinomas are defined as endometrioid carcinoma (EC). Early-stage, well differentiated endometrial carcinomas usually retain expression of estrogen and progesterone receptors (ER and PR, respectively), as advanced stage, poorly differentiated tumors often lack one or both of these receptors. Well-described EC prognosis includes tumor characteristics, such as depth of myometrial invasion. Therefore, in the current study, we evaluated the expression profile of ER and PR isoforms, including ER-α, PR-A and PR–B, in correlation to EC tumor histological depth.MethodsUsing immunohistochemistry and image analysis software, the expression of ER-α, PR-A, PR–B and Ki67 was assessed in endometrial stroma and epithelial glands of superficial, deep and extra-tumoral sections of 15 paraffin embedded EC specimens, and compared to 5 biopsies of non-malignant endometrium.ResultsExpression of PR-A and ER-α was found to be lower in EC compared to nonmalignant tissue, as the stromal expression was dramatically reduced compared to epithelial cells. Expression ratios of both receptors were significantly high in superficial and deep portions of EC; in non-tumoral portion of EC were close to the ratios of nonmalignant endometrium. PR-B expression was low in epithelial glands of EC superficial and deep portions, and high in the extra-tumoral region. Elevated PR-B expression was found in stroma of EC, as well.ConclusionsThe ratio of ER-α and PR-A expression in the epithelial glands and the stroma of EC biopsies may serve as an additional parameter in the histological evaluation of EC tumor.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1155060506119016

Tumor progression, metastasis, and modulators of epithelial–mesenchymal transition in endometrioid endometrial carcinoma: an update

“…PR-B activation by progesterone resulted in tumor suppression by inhibiting cell growth and invasiveness via suppression of the expression of MMPs (1, 2, 7, and 9) and Ets1 transcription factor (Saito et al 2004). The relative overexpression of PR-B without transcriptional repression by PR-A was related to the metastatic potential in ECs (Kreizman-Shefer et al 2014).…”

“…Recently, Kreizman-Shefer et al (2014) proposed loss of ER as an advanced molecular pathology of EC with deregulation of molecular pathways. Common deregulation events include PTEN inactivation by mutation, de novo methylation of ER-A gene and aberrant methylation of CpG islands.…”

“…Expression of either or both isoforms of PR (PR-A and PR-B) was found to be reduced or absent in AEH (Pieczyń ska et al 2011) and in both glands and stroma of EC biopsies in comparison to non-malignant endometrial tissue (Kreizman-Shefer et al 2014). In addition to its growth inhibiting effects, progesterone plays a significant role in regulating invasive properties of EC cells.…”

Progesterone action in breast, uterine, and ovarian cancers

“…In general, hyperplasias express higher levels of PR-A and PR-B (Miyamoto, et al 2004) and comparison of low to high grade endometrial cancers reveals reduced to absent expression of one or both isoforms in epithelia or stroma; these expression profiles are often associated with shorter progression-free survival and overall survival rates (Jongen, et al 2009; Kreizman-Shefer, et al 2014; Leslie, et al 1997; Miyamoto et al 2004; Sakaguchi, et al 2004; Shabani, et al 2007). This silencing of PR expression may be due to hypermethylation of CpG islands within the promoter or first exon regions of the PR gene or to the presence of associated deacetylated histones.…”

The determination of zearalenone and its major metabolites in endometrial cancer tissues

“…Xenoestrogens alter estrogen receptors and disrupt estrogen signaling, which leads to cell proliferation. Xenoestrogens accumulate in the uterus and contribute to cancer [18][19][20][21][22].…”