title: Lynch Syndrome in patients with clear cell and endometrioid cancers of the ovary.
abstract: OBJECTIVE
  Patients with Lynch Syndrome are at an increased risk for a variety of malignancies, including ovarian cancer. Ovarian cancers associated with Lynch Syndrome are predominantly clear cell or endometrioid in histology. Lynch Syndrome is characterized by germline mutations in mismatch repair (MMR) genes. The current study aims to assess the prevalence of loss of MMR expression in patients with endometrioid and clear cell ovarian carcinoma.
  
  
  METHODS
  A retrospective review identified 90 patients with endometrioid and/or clear cell carcinomas. Slides made from tumor tissue microarray blocks were evaluated using immunohistochemical stains with antibodies against MLH1, PMS2, MSH2, and MSH6. Statistical analysis was performed.
  
  
  RESULTS
  Seven of the 90 cases (7.8%) had loss of MMR expression. The mean age of patients with loss of MMR expression (47 years) was significantly younger than those with retained MMR expression (p=0.014). Loss of MMR expression was present in 20% of patients under the age of 53 with clear cell or endometrioid cancers. Genetic studies found that 3 of the 5 patients with loss of MMR expression carried mutations consistent with Lynch Syndrome; acquired hypermethylation of MLH1 was noted in one patient. Six of 7 patients (86%) whose tumors lacked MMR expression had synchronous or metachronous primary malignancies, a significantly greater prevalence than those with retained MMR expression (p<0.001).
  
  
  CONCLUSIONS
  Patients under the age of 53 with clear cell or endometrioid ovarian carcinomas are at a clinically significant risk for loss of MMR expression and Lynch Syndrome; routine screening with immunohistochemical staining should be considered.
authors.affiliation: Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. Electronic address: koah@hawaii.edu.
authors.forename: Koah R
authors.initials: KR
authors.lastname: Vierkoetter
authors.affiliation: Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Asia R
authors.initials: AR
authors.lastname: Ayabe
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: VanDrunen
authors.affiliation: Biostatistics Core, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Hyeong Jun
authors.initials: HJ
authors.lastname: Ahn
authors.affiliation: Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Shimizu
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Keith Y
authors.initials: KY
authors.lastname: Terada
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D012189:Retrospective Studies
keywords: Clear cell ovarian carcinoma; Endometrioid ovarian carcinoma; Lynch Syndrome; Microsatellite instability; Mismatch repair; Ovarian cancer
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