Progesterone receptor isoforms A and B in human epithelial ovarian carcinoma: immunohistochemical and RT-PCR studies

Human epithelial ovarian carcinoma is well-known as a sex steroid-dependent neoplasm, but the possible biological significance of progesterone receptor (PR) in this cancer remains controversial. Recently, two isoforms of human PR, PRA and PRB, have been characterized and different functional characteristics have been reported for these two isoforms. We therefore examined immunohistochemistry (107 cases) and reverse transcription-polymerase chain reaction (RT-PCR) (16 cases) for PRA, PRB, and oestrogen receptor-a (ER-a). Labeling indices (LI) for PRA and PRB were 2.4 and 43.6, respectively, and the difference was statistically significant. PRB LI, but not PRA LI, as well as performance status, stage, and residual tumour turned out to be independent prognostic factors following multivariate analysis. There was also a significant correlation between ER-a LI and PRB LI (r = 0.595, P < 0.0001), suggestive of a possible interaction between these two receptors. RT-PCR also detected the expression of PR isoform transcripts in the same pattern as was observed with immunohistochemistry. Results of these studies indicate that PRA and PRB both mediate distinct pathways of progesterone action in ovarian carcinoma. Moreover, it is important to examine PRB LI as a prognostic factor in the cases of human epithelial ovarian carcinoma. © 2000 Cancer Research Campaign http://www.bjcancer.com

• Publication year

  2000

• Venue

  British Journal of Cancer

• Publication date

  2000-11-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1054/bjoc.2000.1463PMID 11076658PMCID 2363436
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• RT-PCR detected PR isoform transcripts in the same pattern as immunohistochemistry.

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• ER-a labeling index showed a significant positive correlation with PRB labeling index.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• PRB labeling index, but not PRA labeling index, was an independent prognostic factor in multivariate analysis.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• PRB labeling index was markedly higher than PRA labeling index in the ovarian carcinoma specimens examined by immunohistochemistry.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review

• immunohistochemistry

  method

  A tissue-staining method used here to measure receptor labeling in ovarian carcinoma specimens.

  Aliases: IHC

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• labeling index

  measurement

  The proportion of tumor cells showing positive receptor staining in the immunohistochemical assessment.

  Aliases: LI

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• multivariate analysis

  analysis method

  A statistical analysis framework used to test whether receptor measures independently predicted prognosis.

  Aliases: multivariable analysis

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• oestrogen receptor-a

  protein receptor

  The estrogen receptor alpha measured alongside progesterone receptor isoforms in the tumor samples.

  Aliases: ER-a, ER-alpha, estrogen receptor alpha

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• pra

  protein isoform

  The A isoform of the human progesterone receptor examined in ovarian carcinoma tissue.

  Aliases: progesterone receptor A, PR-A

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• prb

  protein isoform

  The B isoform of the human progesterone receptor examined in ovarian carcinoma tissue.

  Aliases: progesterone receptor B, PR-B

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review
• reverse transcription-polymerase chain reaction

  method

  A transcript-detection method used here to assess PR isoform mRNA expression in tumor samples.

  Aliases: RT-PCR

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewAK (4715169a40) review

• Colocalization of progesterone receptors A and B by dual immunofluorescent histochemistry in human endometrium during the menstrual cycle.

  1999cited by this paper
• Estrogen regulation of transforming growth factor-α in ovarian cancer

  1998cited by this paper
• Functionality of the progesterone receptor in ovarian cancer and its regulation by estrogen.

  1998cited by this paper
• Estrogen regulation of transforming growth factor-alpha in ovarian cancer.

  1998cited by this paper
• Expression of Progesterone Receptor Form A and B mRNAs in Uterine Leiomyoma

  1998cited by this paper
• Progesterone receptor status is a significant prognostic variable of progression-free survival in advanced epithelial ovarian cancer.

  1998cited by this paper
• Progesterone receptor subtype B is differentially regulated in human endometrial stroma.

  1998cited by this paper
• Progestin receptor isoforms and prostaglandin dehydrogenase in the endometrium of women using a levonorgestrel-releasing intrauterine system.

  1998cited by this paper
• Selective down-regulation of progesterone receptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action.

  1998cited by this paper
• Differential expression of uterine progesterone receptor forms A and B during the menstrual cycle.

  1997cited by this paper
• Distribution of the A and B forms of the progesterone receptor messenger ribonucleic acid and protein in uterine leiomyomata and adjacent myometrium.

  1997cited by this paper
• Colocalization of 11 beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human epithelia.

  1997cited by this paper
• Mapping and Characterization of the Functional Domains Responsible for the Differential Activity of the A and B Isoforms of the Human Progesterone Receptor*

  1997cited by this paper
• Expression of the chicken progesterone receptor forms A and B is differentially regulated by estrogen in vivo.

  1997cited by this paper
• Responses in the brain of estrogen receptor a-disrupted mice

  1997cited by this paper
• Responses in the brain of estrogen receptor alpha-disrupted mice.

  1997cited by this paper
• Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma.

  1996cited by this paper
• Estrogen and progesterone receptor status as prognostic indicators in patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary.

  1996cited by this paper
• Progesterone receptor A and B protein expression in human breast cancer.

  1996cited by this paper
• Expression of progesterone receptor form A and B mRNAs in gynecologic malignant tumors.

  1995cited by this paper
• Preferential Stimulation of Human Progesterone Receptor B Expression by Estrogen in T-47D Human Breast Cancer Cells (*)

  1995cited by this paper
• Inhibitory cross-talk between steroid hormone receptors: differential targeting of estrogen receptor in the repression of its transcriptional activity by agonist- and antagonist-occupied progestin receptors

  1995cited by this paper
• The A and B isoforms of the human progesterone receptor operate through distinct signaling pathways within target cells

  1994cited by this paper
• Long-term survival in advanced ovarian cancer after cytoreduction and chemotherapy treatment.

  1994cited by this paper
• Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function.

  1993cited by this paper
• Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program.

  1993cited by this paper
• Steroid receptors in ovarian carcinoma: immunohistochemical determination may lead to new aspects.

  1992cited by this paper
• Endocrine factors in common epithelial ovarian cancer.

  1991cited by this paper
• Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience.

  1991cited by this paper
• Molecular action of progesterone.

  1990cited by this paper
• Multihormonal regulation of the progesterone receptor in MCF-7 human breast cancer cells: interrelationships among insulin/insulin-like growth factor-I, serum, and estrogen.

  1990cited by this paper
• Two distinct estrogen‐regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B.

  1990cited by this paper
• Oestrogen and progesterone receptor content as a prognostic factor in advanced epithelial ovarian carcinoma

  1990cited by this paper
• Progestin regulation of cellular proliferation.

  1990cited by this paper
• Study of ovarian tumors treated at Nagoya University Hospital, 1965-1988.

  1990cited by this paper
• Importance of steroid receptors and aromatase activity in the prognosis of ovarian cancer: high tumor progesterone receptor levels correlate with longer survival.

  1989cited by this paper
• Clinical correlation of hormone receptor status in epithelial ovarian cancer.

  1989cited by this paper
• The relationship of steroid receptor expression to nuclear DNA distribution and clinicopathological characteristics in epithelial ovarian tumors.

  1989cited by this paper
• Steroid receptors in epithelial ovarian carcinoma: relation to clinical parameters and survival.

  1988cited by this paper
• The impact of aggressive debulking surgery and cisplatin-based chemotherapy on progression-free survival in stage III and IV ovarian carcinoma.

  1988cited by this paper
• The steroid and thyroid hormone receptor superfamily.

  1988cited by this paper
• Monoclonal antibodies to human progesterone receptor: characterization by biochemical and immunohistochemical techniques.

  1987cited by this paper
• Steroid receptor content in human ovarian tumors: survival of patients with ovarian carcinoma related to steroid receptor content.

  1986cited by this paper
• Cytoreductive surgery in ovarian carcinoma: feasibility and morbidity.

  1986cited by this paper
• Cloning of the chicken progesterone receptor.

  1986cited by this paper
• Cytoreductive surgery in ovarian carcinoma: Feasibility and morbidity

  1986cited by this paper
• Prognostic factors in advanced ovarian carcinoma.

  1986cited by this paper
• Prognostic relevance of ploidy, proliferation, and resistance-predictive tests in ovarian carcinoma.

  1985cited by this paper
• Progestin Therapy of Endometrial, Breast and Ovarian Carcinoma

  1984cited by this paper
• Prognostic significance of nuclear DNA content in serous ovarian tumors.

  1984cited by this paper
• In situ photolinked nuclear progesterone receptors of human breast cancer cells: subunit molecular weights after transformation and translocation.

  1983cited by this paper
• Cytoplasmic progesterone and estradiol receptors in normal, hyperplastic, and carcinomatous endometria: therapeutic implications.

  1981cited by this paper
• Is a functional estrogen receptor always required for progesterone receptor induction in breast cancer?

  1981cited by this paper
• The role of progesterone receptors in the management of advanced breast cancer

  1980cited by this paper
• Do Estrogen and Progesterone Receptors (E2R and PR) in Metastasizing Endometrial Cancers Predict the Response to Gestagen Therapy?

  1980cited by this paper
• The value of estrogen and progesterone receptors in the treatment of breast cancer

  1980cited by this paper
• Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy.

  1978cited by this paper
• Steroid receptors in human breast cancer.

  1978cited by this paper

• Biomarkers in high grade serous ovarian cancer.

  2024cites this paper
• Differential expression analysis in epithelial ovarian cancer using functional genomics and integrated bioinformatics approaches

  2023cites this paper
• Re-evaluating the role of progesterone in ovarian cancer: is progesterone always protective?

  2023cites this paper
• Immunohistochemical features of canine ovarian papillary adenocarcinoma and utility of cell block technique for detecting neoplastic cells in body cavity effusions

  2022cites this paper
• Sex steroid hormones and DNA repair regulation: implications on cancer treatment responses.

  2022cites this paper
• Progesterone Receptors Promote Quiescence & Ovarian Cancer Cell Phenotypes via DREAM in p53-Mutant Fallopian Tube Models.

  2021cites this paper
• Hormone therapy for ovarian cancer: Emphasis on mechanisms and applications

  2021cites this paper
• Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma

  2021cites this paper
• Progesterone decreases ovarian cancer cells migration and invasion.

  2020cites this paper
• MODULATION OF GENES AND PROTEIN LOCALIZATION FOR ESTROGEN AND PROGESTERONE RECEPTORS IN CYCLOPHOSPHAMIDE-EFFECTED OVARY BY TOCOTRIENOLS SUPPLEMENTATION

  2019cites this paper
• Correlation of NRF2 and progesterone receptor and its effects on ovarian cancer biology

  2019cites this paper
• C-ERB-2, P53, Ki67 Proteins and Receptors of Estrogen and Progesterone on the Prognosis of Epithelial Ovarian Cancer

  2019cites this paper
• Estrogen receptor β is associated with expression of cancer associated genes and survival in ovarian cancer

  2018cites this paper
• Progesterone action in breast, uterine, and ovarian cancers.

  2015influential citation
• Active FOXO1 Is a Key Determinant of Isoform-Specific Progesterone Receptor Transactivation and Senescence Programming

  2015influential citation
• Ki-67 as an independent prognostic factor in an unselected cohort of patients with ovarian cancer: results of an explorative, retrospective study.

  2014cites this paper
• [Applicability of selective progesterone receptor modulators in the treatment of uterine leiomyomata and their future role in the field of gynecology].

  2013cites this paper
• Fluorescent Ligand for Human Progesterone Receptor Imaging in Live Cells

  2013cites this paper
• Progesterone receptors induce FOXO1-dependent senescence in ovarian cancer cells

  2013cites this paper
• The Role of Luteal Phase Fallopian Tube Epithelium in High-grade Ovarian Serous Carcinoma

  2012cites this paper
• Steroid hormone receptor expression in ovarian cancer: progesterone receptor B as prognostic marker for patient survival

  2012influential citation
• Evaluation of a hormone receptor‐positive ovarian carcinoma subtype with a favourable prognosis by determination of progesterone receptor and oestrogen receptor 1 mRNA expression in formalin‐fixed paraffin‐embedded tissue

  2011cites this paper
• Cytoplasmic expression of estrogen receptor beta (ERβ) predicts poor clinical outcome in advanced serous ovarian cancer.

  2011cites this paper
• Cancer Therapy : Preclinical Forkhead Transcription Factor FOXO 1 is a Direct Target of Progestin to Inhibit Endometrial Epithelial Cell Growth

  2011cites this paper
• Decreased progesterone receptor isoform expression in luteal phase fallopian tube epithelium and high-grade serous carcinoma

  2011cites this paper
• Molecular markers in epithelial ovarian cancer: their role in prognosis and therapy.

  2010cites this paper
• Forkhead Transcription Factor FOXO1 is a Direct Target of Progestin to Inhibit Endometrial Epithelial Cell Growth

  2010cites this paper
• Steroid and Xenobiotic Receptor (SXR) as a possible prognostic marker in epithelial ovarian cancer

  2010cites this paper
• Estrogen regulation and physiopathologic significance of alternative promoters in breast cancer.

  2010cites this paper
• Correlation Between Immunohistochemical Biomarkers Expression and Prognosis of Ovarian Carcinomas in Tunisian Patients

  2010cites this paper
• Induction of senescence by progesterone receptor-B activation in response to cAMP in ovarian cancer cells.

  2009cites this paper
• Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the ovarian cancer association consortium pooled analysis

  2008cites this paper
• The human progesterone receptor shows evidence of adaptive evolution associated with its ability to act as a transcription factor.

  2008cites this paper
• Clinicopathological significance of circadian rhythm‐related gene expression levels in patients with epithelial ovarian cancer

  2008cites this paper
• Loss of estrogen receptor β isoform expression and its correlation with aberrant DNA methylation of the 5′‐untranslated region in human epithelial ovarian carcinoma

  2008cites this paper
• Hormonal therapy in ovarian cancer

  2007cites this paper
• Promoter methylation status of the Cyclin D2 gene is associated with poor prognosis in human epithelial ovarian cancer

  2007cites this paper
• Analysis of the expression of estrogen receptor, progesterone receptor and chicken ovalbumin upstream promoter-transcription factor I in ovarian epithelial cancers and normal ovaries.

  2007cites this paper
• Decreased expression of RIZ1 and its clinicopathological significance in epithelial ovarian carcinoma: Correlation with epigenetic inactivation by aberrant DNA methylation

  2007cites this paper
• Hormonal therapy in ovarian cancer

  2006cites this paper
• Progesterone receptor isoforms as a prognostic marker in human endometrial carcinoma

  2006cites this paper
• Contribution of immunohistochemistry in prognostic assessment of epithelial ovarian carcinoma --review of the literature I.

  2006cites this paper
• Les progestatifs en cancérologie mammaire : Isoformes du récepteur de la progestérone : rôle dans la cancérogenèse mammaire

  2006cites this paper
• Estrogen-induced loss of progesterone receptor expression in normal and malignant ovarian surface epithelial cells

  2005cites this paper
• Modulation of Folate Receptor-alpha by Glucocorticoid Receptor and Progesterone Receptor

  2005cites this paper
• Expression of steroid hormone receptors in BRCA1-associated ovarian carcinomas.

  2005cites this paper
• Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications.

  2005cites this paper
• Expression of estrogen-responsive finger protein (Efp) is associated with advanced disease in human epithelial ovarian cancer.

  2005cites this paper
• Expression of progesterone receptor is a favorable prognostic marker in ovarian cancer.

  2005cites this paper
• Estrogen and progesterone receptors in ovarian epithelial tumors.

  2004cites this paper
• Sex-steroid hormones, gonadotropin and ovarian carcinogenesis: a review of epidemiological and experimental data

  2004cites this paper
• Nuclear receptor and cofactor expression in female reproductive tissues

  2004cites this paper
• Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition.

  2004cites this paper
• Possible effects of progesterone on human central nervous system and neurogenic tumors

  2004cites this paper
• Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation.

  2004cites this paper
• Decreased Expression of 14-3-3σ Is Associated with Advanced Disease in Human Epithelial Ovarian Cancer

  2004cites this paper
• Telomerase Reverse Transcriptase (hTERT) mRNA and Telomerase RNA (hTR) as Targets for Downregulation of Telomerase Activity

  2004cites this paper
• Estrogen, Progesterone and Epithelial Ovarian Cancer

  2003cites this paper
• Loss of coordinated androgen regulation in nonmalignant ovarian epithelial cells with BRCA1/2 mutations and ovarian cancer cells.

  2003cites this paper
• Non-genomic progesterone receptors in the mammalian ovary: some unresolved issues.

  2003cites this paper
• Progesterone production and actions in the human central nervous system and neurogenic tumors.

  2002cites this paper
• Differential Expression of Progesterone Receptor Isoforms A and B in the Normal Ovary, and in Benign, Borderline, and Malignant Ovarian Tumors

  2002cites this paper
• Progesterone Receptor A and B Isoforms in the Human Breast and Its Disorders

  2001cites this paper
• Expression of 5α‐Reductases in Human Epithelial Ovarian Cancer: Its Correlation with Androgen Receptor Status

  2001cites this paper
• Reproductive Biology and Endocrinology Open Access Estrogen, Progesterone and Epithelial Ovarian Cancer

  year unknowncites this paper