Abnormal mismatch repair and other clinicopathologic predictors of poor response to progestin treatment in young women with endometrial complex atypical hyperplasia and well‐differentiated endometrial adenocarcinoma: a consecutive case series

• Published in: BJOG : an international journal of obstetrics and gynaecology Vol. 124; no. 10; pp. 1576 - 1583
• Main Authors: Zakhour, M, Cohen, JG, Gibson, A, Walts, AE, Karimian, B, Baltayan, A, Aoyama, C, Garcia, L, Dhaliwal, SK, Elashoff, D, Amneus, M, Walsh, C
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2017
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Age; Biomarkers; Body mass; Body mass index; Colorectal cancer; Complex atypical hyperplasia; DNA Mismatch Repair; DNA repair; Endometrial cancer; Endometrial Hyperplasia - drug therapy; Endometrial Hyperplasia - genetics; Endometrial Hyperplasia - pathology; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Endometrium; Female; Genetic disorders; Gynecology; Health risk assessment; Hormone replacement therapy; Humans; Hyperplasia; Immunohistochemistry; Invasiveness; Lynch syndrome; Malignancy; Medical prognosis; Middle Aged; Mismatch repair; MMR protein; Progestin; Progestins - therapeutic use; Protein expression; Womens health; United States > US; endometrial cancer; mismatch repair; Complex atypical hyperplasia; Lynch syndrome
• ISSN: 1470-0328; 1471-0528
• DOI: 10.1111/1471-0528.14491

Objective To report the response to progestin therapy in young women with endometrial complex atypical hyperplasia (CAH) or FIGO grade 1 endometrial adenocarcinoma (FIGO 1 EAC) based on clinicopathologic features, including abnormal DNA mismatch repair (MMR) by immunohistochemistry (IHC). Design Consecutive case series. Setting Olive View‐UCLA Medical Center in Sylmar, CA, USA, and Cedars‐Sinai Medical Center in Los Angeles, CA, USA. Population Women ≤55 years old with CAH or FIGO 1 EAC. Methods Response to progestin therapy in 84 consecutive patients was assessed based on clinicopathologic factors, including age, body mass index (BMI), initial histology, and IHC staining for MMR proteins. Main outcome measures Rates of abnormal MMR protein expression and response to progestin therapy were determined. Results Six (7%) patients had abnormal IHC staining, of whom five (83%) had FIGO 1 EAC at initial diagnosis. Following progestin treatment, none of the endometrial lesions in patients with abnormal IHC for MMR proteins had resolution of hyperplasia or malignancy, in contrast to 41 (53%) with normal staining (P = 0.028). Age ≤40 years and initial lesion (CAH versus FIGO 1 EAC) were predictors of response to progestin; BMI was not. Conclusions In this cohort, 7% of women ≤55 years of age with CAH or FIGO 1 EAC had loss of MMR proteins by IHC. These patients had a higher incidence of invasive cancer and a lower incidence of resolution with progestin therapy. Tweetable Abnormal MMR protein expression predicts poor response to progestins in young women with CAH or FIGO 1 EAC. Tweetable Abnormal MMR protein expression predicts poor response to progestins in young women with CAH or FIGO 1 EAC.