title: 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.
abstract: 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).
  
  
  
  Consecutive case series.
  
  
  
  Olive View-UCLA Medical Center in Sylmar, CA, USA, and Cedars-Sinai Medical Center in Los Angeles, CA, USA.
  
  
  
  Women ≤55 years old with CAH or FIGO 1 EAC.
  
  
  
  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.
  
  
  
  Rates of abnormal MMR protein expression and response to progestin therapy were determined.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Abnormal MMR protein expression predicts poor response to progestins in young women with CAH or FIGO 1 EAC.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of California Los Angeles Medical Center, Los Angeles, CA, USA.|Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Zakhour
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of California Los Angeles Medical Center, Los Angeles, CA, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Cohen
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of California Los Angeles Medical Center, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gibson
authors.affiliation: Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Walts
authors.affiliation: Department of Pathology & Laboratory Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Karimian
authors.affiliation: Department of Pathology & Laboratory Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Baltayan
authors.affiliation: Department of Pathology & Laboratory Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Aoyama
authors.affiliation: Department of Obstetrics & Gynecology, Olive View-UCLA Medical Center, Sylmar, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Garcia
authors.affiliation: Department of Medicine Statistics Core, University of California Los Angeles Medical Center, Los Angeles, CA, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Dhaliwal
authors.affiliation: Department of Medicine Statistics Core, University of California Los Angeles Medical Center, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Elashoff
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Olive View-UCLA Medical Center, Sylmar, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Amneus
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Walsh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D053843:DNA Mismatch Repair; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011372:Progestins / Q000627:therapeutic use*
chemical_list: D011372:Progestins
keywords: Complex atypical hyperplasia; Lynch syndrome; endometrial cancer; mismatch repair