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Type: Journal article
Title: High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the colon cancer family registry
Author: Rosty, C.
Walsh, M.
Lindor, N.
Thibodeau, S.
Mundt, E.
Gallinger, S.
Aronson, M.
Pollett, A.
Baron, J.
Pearson, S.
Clendenning, M.
Walters, R.
Nagler, B.
Crawford, W.
Young, J.
Winship, I.
Win, A.
Hopper, J.
Jenkins, M.
Buchanan, D.
Citation: Familial Cancer, 2014; 13(4):573-582
Publisher: Springer Verlag
Issue Date: 2014
ISSN: 1389-9600
Statement of
Christophe Rosty, Michael D. Walsh, Noralane M. Lindor, Stephen N. Thibodeau, Erin Mundt, Steven Gallinger, Melyssa Aronson, Aaron Pollett, John A. Baron, Sally Pearson, Mark Clendenning, Rhiannon J. Walters, Belinda N. Nagler, William J. Crawford, Joanne P. Young, Ingrid Winship, Aung Ko Win, John L. Hopper, Mark A. Jenkins and Daniel D. Buchanan
Abstract: The question of whether prostate cancer is part of the Lynch syndrome spectrum of tumors is unresolved. We investigated the mismatch repair (MMR) status and pathologic features of prostate cancers diagnosed in MMR gene mutation carriers. Prostate cancers (mean age at diagnosis = 62 ± SD = 8 years) from 32 MMR mutation carriers (23 MSH2, 5 MLH1 and 4 MSH6) enrolled in the Australasian, Mayo Clinic and Ontario sites of the Colon Cancer Family Registry were examined for clinico-pathologic features and MMR-deficiency (immunohistochemical loss of MMR protein expression and high levels of microsatellite instability; MSI-H). Tumor MMR-deficiency was observed for 22 cases [69 %; 95 % confidence interval (CI) 50–83 %], with the highest prevalence of MMR-deficiency in tumors from MSH2 mutation carriers (19/23, 83 %) compared with MLH1 and MSH6 carriers combined (3/9, 33 %; p = 0.01). MMR-deficient tumors had increased levels of tumor infiltrating lymphocytes compared with tumors without MMR-deficiency (p = 0.04). Under the assumption that tumour MMR-deficiency occurred only because the cancer was caused by the germline mutation, mutation carriers are at 3.2-fold (95 % CI 2.0–6.3) increased risk of prostate cancer, and when assessed by gene, the relative risk was greatest for MSH2 carriers (5.8, 95 % CI 2.6–20.9). Prostate cancer was the first or only diagnosed tumor in 37 % of carriers. MMR gene mutation carriers have at least a twofold or greater increased risk of developing MMR-deficient prostate cancer where the risk is highest for MSH2 mutation carriers. MMR IHC screening of prostate cancers will aid in identifying MMR gene mutation carriers.
Keywords: Prostate cancer; Lynch syndrome; Mismatch repair deficiency; Mismatch repair gene; mutations; Tumor infiltrating lymphocytes
Rights: © Springer Science+Business Media Dordrecht 2014
DOI: 10.1007/s10689-014-9744-1
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