TY - JOUR
T1 - High glucocorticoid receptor expression in the sarcomatous versus carcinomatous elements of Mullerian carcinosarcomas
AU - Kurnit, Katherine C.
AU - Steiner, Meghan
AU - Lastra, Ricardo R.
AU - Weroha, S. John
AU - Cursio, John
AU - Lengyel, Ernst
AU - Fleming, Gini F.
AU - Conzen, Suzanne D.
N1 - Funding Information:
The authors would like to acknowledge Dr. Jennifer Veneris for her contributions to this work. Ernst Lengyel receives research funding from AbbVie and Arsenal Bio to perform translational ovarian cancer research that is completely unrelated to this study. Suzanne Conzen is an inventor on patents licensed by The University of Chicago to Corcept Therapeutics regarding a method to use glucocorticoid receptor modulators as therapies for triple-negative breast cancer and prostate cancer that is not directly relevant to Mullerian carcinosarcomas. Gini Fleming has served on an advisory board to GSK on a topic not directly related to this study.
Funding Information:
GFF, SDC, SJW, and EL acknowledge support from the Mayo Clinic SPORE in Ovarian Cancer Developmental Research Program, Pilot Study Award (5P50CA136393-09); SDC and GFF received funding from NIH R21CA223426-02. KCK, MS, JTV, RRL, EL, GFF acknowledge support from the University of Chicago Comprehensive Cancer Center Core Immunohistochemistry Facility, grant #5P30CA014599-46.
Publisher Copyright:
© 2022
PY - 2022/6
Y1 - 2022/6
N2 - Glucocorticoid receptor can be associated with poor prognosis among a variety of solid tumors in the absence of other nuclear hormone receptors. Our objective was to characterize differences in glucocorticoid receptor (GR), estrogen receptor (ER), progesterone receptor (PR), and androgen receptor expression in the sarcomatous versus carcinomatous components of ovarian and uterine carcinosarcomas. Eighteen patients diagnosed with Mullerian carcinosarcoma between May 2009 and August 2014 were included. Nuclear receptor expression was evaluated by immunohistochemistry using whole tissue specimens. Receptor expression was quantified using the H-score. Mean H-scores were compared between the sarcomatous and carcinomatous components of tumors using Wilcoxon signed-rank tests. We found that GR expression was significantly higher in the sarcomatous components than in the carcinomatous components of the cancers (mean H score 144.4 vs 38.9, p = 0.002). Conversely, ER (3.1 vs 63.1, p = 0.002) and PR (1.7 vs 47.2, p < 0.0001) expression were significantly decreased in the sarcomatous component compared to the carcinomatous component. Androgen receptor expression was low overall (0 versus 2.8, p = 0.04). We hypothesize that GR-high, ER/PR-low expression is associated with epithelial to mesenchymal transition in the sarcomatous cells and may serve as a potential therapeutic target.
AB - Glucocorticoid receptor can be associated with poor prognosis among a variety of solid tumors in the absence of other nuclear hormone receptors. Our objective was to characterize differences in glucocorticoid receptor (GR), estrogen receptor (ER), progesterone receptor (PR), and androgen receptor expression in the sarcomatous versus carcinomatous components of ovarian and uterine carcinosarcomas. Eighteen patients diagnosed with Mullerian carcinosarcoma between May 2009 and August 2014 were included. Nuclear receptor expression was evaluated by immunohistochemistry using whole tissue specimens. Receptor expression was quantified using the H-score. Mean H-scores were compared between the sarcomatous and carcinomatous components of tumors using Wilcoxon signed-rank tests. We found that GR expression was significantly higher in the sarcomatous components than in the carcinomatous components of the cancers (mean H score 144.4 vs 38.9, p = 0.002). Conversely, ER (3.1 vs 63.1, p = 0.002) and PR (1.7 vs 47.2, p < 0.0001) expression were significantly decreased in the sarcomatous component compared to the carcinomatous component. Androgen receptor expression was low overall (0 versus 2.8, p = 0.04). We hypothesize that GR-high, ER/PR-low expression is associated with epithelial to mesenchymal transition in the sarcomatous cells and may serve as a potential therapeutic target.
KW - Carcinosarcoma
KW - Estrogen receptor
KW - Glucocorticoid receptor
KW - Progesterone receptor
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U2 - 10.1016/j.gore.2022.100987
DO - 10.1016/j.gore.2022.100987
M3 - Article
AN - SCOPUS:85129465747
SN - 2211-338X
VL - 41
JO - Gynecologic Oncology Reports
JF - Gynecologic Oncology Reports
M1 - 100987
ER -