Biomarkers of progestin therapy resistance and endometrial hyperplasia progression.
OBJECTIVE
We sought to identify biomarkers associated with progestin therapy resistance and persistence/progression of endometrial hyperplasia.


METHODS
We performed a nested case-control study among women with complex (n = 73) and atypical (n = 41) hyperplasia treated with oral progestin, followed up 2-6 months for persistence/progression. We evaluated index endometrial protein expression for progesterone receptor isoform A, progesterone receptor isoform B (PRB), PTEN, Pax-2, and Bcl-2. Odds ratios and 95% confidence intervals (CIs) were estimated.


RESULTS
Among women with atypical hyperplasia, high PRB expression was associated with 90% decreased risk of persistence/progression (95% CI, 0.01-0.8). High expression of progesterone receptor A and PRB suggested decreased risk of persistence/progression (odds ratio, 0.1; 95% CI, 0.02-1.0). These findings were not observed among women with complex hyperplasia. No associations were found with PTEN, Pax-2, and Bcl-2 protein expression.


CONCLUSIONS
PRB expression shows promise as a biomarker of progestin response. Further research is warranted to understand how PRB expression may guide treatment decisions.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. kupson@u.washington.edu
Kristen
K
Upson
Kimberly H
KH
Allison
Susan D
SD
Reed
Carolyn D
CD
Jordan
Katherine M
KM
Newton
Elizabeth M
EM
Swisher
Jennifer A
JA
Doherty
Rochelle L
RL
Garcia
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D051762:PAX2 Transcription Factor / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011372:Progestins / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D016037:Single-Blind Method; D016896:Treatment Outcome
D015415:Biomarkers; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D011372:Progestins; D019253:Proto-Oncogene Proteins c-bcl-2; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human