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. Bonneterre, J., Hutt, E., Bosq, J., Graham, J. D., Powell, M. A., Leblanc, E., Fujiwara, K., Herzog, T. J., Coleman, R. L., Clarke, C. L., Gilles, E. M., Zukiwski, A. A., & Monk, B. J. Gynecol Oncol, 138(3):663–7, September, 2015.
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 [link]Paper  doi  abstract   bibtex   
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-alpha (ERalpha), 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 (APR(pos)) tumors were prospectively defined as any tumor with \textbackslashtextbackslashtextgreater5% countable malignant cells with an aggregated nuclear pattern. Tumor APR status was analyzed against other biomarkers including ERalpha 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 APR(pos). Percent of ER(pos) cells correlated with % PR(pos) malignant cells (p=0.001, rho=0.44). APR positivity did not correlate with % PR(pos) 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 APR(pos). 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.
@article{bonneterre_development_2015,
	title = {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},
	volume = {138},
	issn = {1095-6859 (Electronic) 0090-8258 (Linking)},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/26142884},
	doi = {10.1016/j.ygyno.2015.06.037},
	abstract = {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-alpha (ERalpha), 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 (APR(pos)) tumors were prospectively defined as any tumor with {\textbackslash}textbackslashtextgreater5\% countable malignant cells with an aggregated nuclear pattern. Tumor APR status was analyzed against other biomarkers including ERalpha 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 APR(pos). Percent of ER(pos) cells correlated with \% PR(pos) malignant cells (p=0.001, rho=0.44). APR positivity did not correlate with \% PR(pos) 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 APR(pos). 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.},
	number = {3},
	journal = {Gynecol Oncol},
	author = {Bonneterre, J. and Hutt, E. and Bosq, J. and Graham, J. D. and Powell, M. A. and Leblanc, E. and Fujiwara, K. and Herzog, T. J. and Coleman, R. L. and Clarke, C. L. and Gilles, E. M. and Zukiwski, A. A. and Monk, B. J.},
	month = sep,
	year = {2015},
	keywords = {Carcinoma, Endometrial Neoplasms/*chemistry/metabolism/pathology, Endometrioid/*chemistry/metabolism/pathology, Estrogen Receptor alpha/analysis/metabolism, Female, Formaldehyde, Humans, Immunohistochemistry, Ki-67 Antigen/analysis/metabolism, Neoplasm Grading, Neoplasm Staging, Paraffin Embedding, Progesterone/*analysis/metabolism, Prognosis, Receptors, Tissue Fixation},
	pages = {663--7},
}
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