Prostate Carcinomas Arising in Lynch Syndrome Patients Frequently Show Concordant Mismatch Repair Deficiency
Christophe Rosty, Michael D Walsh, Mark Clendenning, Joanne P Young, Noralane Lindor, John L Hopper, Mark A Jenkins, Daniel D Buchanan. Queensland Institute of Medical Research, Brisbane, Australia; University of Queensland, Brisbane, Australia; Envoi Pathology, Brisbane, Australia; Sullivan Nicolaides Pathology, Brisbane, Australia; Mayo Clinic, Scottsdale, AZ; University of Melbourne, Melbourne, Australia
Background: Lynch syndrome (LS) is an inherited predisposition to developing carcinomas of the colorectum, endometrium, small intestine, stomach, pancreatico-biliary tract, ovary and upper urinary tract. Mutations in mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 underpin Lynch syndrome. While prostate adenocarcinoma is not considered one of the spectrum tumours for LS, case reports have documented loss of MMR expression in prostate carcinoma from LS patients.
Design: We sought to investigate the incidence of MMR loss of expression in prostate carcinoma from LS carriers enrolled in the Australasian Colorectal Cancer Family Registry (ACCFR). MMR immunohistochemistry was performed on tissue samples from prostate carcinoma (biopsies and prostatectomy specimens).
Results: There were 15 prostate carcinomas from 15 LS patients (mean age = 62.2 years). Eight individuals had been diagnosed with colorectal carcinoma, one individual with pancreatic carcinoma, and prostate carcinoma was the only malignancy diagnosed in five individuals. MMR-deficiency was detected in 12/15 (80%) cases: MLH1/PMS2 loss in 2, MSH2/MSH6 loss in 10. The pattern of loss of MMR expression was consistent with the individual's germline mutation in all cases. All fifteen adenocarcinomas were of acinar type: 1 with Gleason score (GS) 6 (this tumour had normal MMR expression and arose in an MSH6 mutation carrier), 7 with GS 7, and 7 with GS ≥8. Tumour infiltrating lymphocytes were noted in low numbers in seven of the tumours.
Conclusions: These findings indicate that MMR-deficiency is commonly observed in prostate adenocarcinomas arising in Lynch syndrome mutation carriers. The prostate tumours with MMR-deficiency from these carriers demonstrated frequent high histologic grade, a feature in common with MMR-deficient cancers from other sites. Prostate carcinoma was the only tumour in 5/15 MMR carriers.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 2:00 PM
Proffered Papers: Section A, Monday Afternoon