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.
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-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 (APR(pos)) 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 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.
authors.affiliation: Centre Oscar-Lambret, 3 Rue Frédéric Combemale, 59000 Lille, France. Electronic address: j-bonneterre@o-lambret.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bonneterre
authors.affiliation: Centre Oscar-Lambret, 3 Rue Frédéric Combemale, 59000 Lille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Hutt
authors.affiliation: Institut Gustave Roussy, 114 Rue Édouard Vaillant, 94805 Villejuif, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bosq
authors.affiliation: Centre for Cancer Research, Westmead Millennium Institute Sydney Medical School - Westmead, University of Sydney, New South Wales, Australia.
authors.forename: J Dinny
authors.initials: JD
authors.lastname: Graham
authors.affiliation: Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Powell
authors.affiliation: Centre Oscar-Lambret, 3 Rue Frédéric Combemale, 59000 Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Leblanc
authors.affiliation: Saitama Medical University International Medical Center, Hidaka Campus, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: University of Cincinnati Cancer Institute, 3255 Eden Ave. Suite 250, Cincinnati, OH 45267, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Herzog
authors.affiliation: The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.affiliation: Centre for Cancer Research, Westmead Millennium Institute Sydney Medical School - Westmead, University of Sydney, New South Wales, Australia.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Clarke
authors.affiliation: Invivis Pharmaceuticals, 547 Meadow Road, Bridgewater, NJ 08807, USA; Arno Therapeutics, 200 Route 31 Flemington, NJ 08822, USA.
authors.forename: Erard M
authors.initials: EM
authors.lastname: Gilles
authors.affiliation: Arno Therapeutics, 200 Route 31 Flemington, NJ 08822, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Zukiwski
authors.affiliation: University of Arizona Cancer Center-Phoenix, Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
mesh_terms: D018269:Carcinoma, Endometrioid / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000378:metabolism; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011379:Prognosis; D011980:Receptors, Progesterone / Q000032:analysis* / Q000378:metabolism; D016707:Tissue Fixation
chemical_list: D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone; D005557:Formaldehyde
keywords: Activated progesterone receptor; Anti-progestin; Endometrial cancer; Onapristone; Progestin