title: Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression.
abstract: OBJECTIVE
  This study examines premenopausal and early menopause patients in a unique population with endometrial cancer and loss of mismatch repair (MMR) gene expression. The purpose is to compare clinical and pathologic differences in patients with loss of expression (LOE) to those with normal expression (NE).
  
  
  METHODS
  Endometrial cancer patients under age 60 in-between 1998 and 2008 were identified from a single tumor registry. Clinical and pathologic data were abstracted from records. Staining for expression of MSH6, MSH2, MLH1, and PMS2 were performed on archived tissue blocks. Statistical analysis was performed.
  
  
  RESULTS
  158 patients were analyzed; 58% Asian, 34% Pacific Islander, and 8% Caucasian. 31 demonstrated LOE of at least one MMR gene; 127 retained NE. 50% Caucasian, 21.9% Asian, and 12.5% Pacific Island populations had LOE of one or more MMR genes. LOE was found to have a higher incidence of Grade III (p=0.0013) and stage 3-4 tumors (p=0.0079), mean depth of myometrial invasion (p=0.0019), lymphovascular space invasion (p=0.0020), nodal metastases (p=0.0157), and a lower incidence of Grade I (p=0.0020) and stage 1A tumors (p=0.0085). LOE had a significantly lower mean BMI (p=0.0001). 35% of patients in the NE vs zero in the LOE group had a BMI greater than 40.
  
  
  CONCLUSIONS
  Younger patients with LOE endometrial cancer appear to represent a clinically significant subgroup of patients without features characteristically found in classic type 1 endometrial cancer generally demonstrating lower BMI and tumors associated with poor prognostic characteristics. It is unclear if the distinctive ethnicity found in Hawaii has a significant impact on outcome. Further investigation is necessary to identify appropriate treatment strategies.
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA. KassondraG@gmail.com
authors.forename: Kassondra S
authors.initials: KS
authors.lastname: Grzankowski
authors.forename: David M
authors.initials: DM
authors.lastname: Shimizu
authors.forename: Chieko
authors.initials: C
authors.lastname: Kimata
authors.forename: Michael
authors.initials: M
authors.lastname: Black
authors.forename: Keith Y
authors.initials: KY
authors.lastname: Terada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000328:Adult; D044466:Asian People / Q000235:genetics; D002296:Carcinosarcoma / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D012189:Retrospective Studies; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes