Development of a technique to detect the activated form of the progesterone receptor and correlation with clinical and histopathological characteristics of endometrioid adenocarcinoma of the uterine corpus

Jacques Bonneterrea, , , Emilie Hutta, Jacques Bosqb, J. Dinny Grahamc, Matthew A. Powelld, Eric Leblanca, Keiichi Fujiwarae, Thomas J. Herzogf, Robert L. Colemang, Christine L. Clarkec, Erard M. Gillesh, i, Alexander A. Zukiwskii, Bradley J. Monkj

Objective

Hormonal therapy is generally reserved for patients with endometrial cancers that fail cytotoxic chemotherapy, but there is a lack of sufficiently sensitive diagnostics to identify potential responders. We sought to develop a diagnostic technique to detect activated progesterone receptors (APR) in endometrial cancers using routine immunohistochemistry (IHC) and to correlate the presence of APR with other histopathological features and clinical disease stage.

Methods

Seventy-two tumor block specimens from patients with endometrial cancer were processed with conventional IHC methods for estrogen receptor-α (ERα), progesterone receptor (PR) and Ki67, a marker of proliferation. Tumor specimens were analyzed for the PR nuclear distribution patterns in individual tumor cells: APR positive (APRpos) tumors were prospectively defined as any tumor with > 5% countable malignant cells with an aggregated nuclear pattern. Tumor APR status was analyzed against other biomarkers including ERα expression, Ki67 and tumor grade.

Results

Fifty-six of 72 samples were endometrioid. Twenty-six of 49 PR-positive endometrioid tumors (53%; 95% CI 39–67%) were APRpos. Percent of ERpos cells correlated with % PRpos malignant cells (p = 0.001, rho = 0.44). APR positivity did not correlate with % PRpos cells in a given tumor, nor did it correlate with % Ki67 positivity; APR positivity was independent of disease stage and tumor grade (p = NS).

Conclusions

In this study, approximately half of endometrioid tumors were APRpos. APR is independent of histopathological and other known risk factors. Refining conventional PR detection has the potential to prospectively identify patients with endometrial cancer who may benefit from anti-progestin therapy.

Gynecologic Oncology

Volume 138, Issue 3, September 2015, Pages 663–667