Tags

Type your tag names separated by a space and hit enter

High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the colon cancer family registry.
Fam Cancer 2014; 13(4):573-82FC

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.

Authors+Show Affiliations

Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology and Centre for Epidemiology and Biostatistics, University of Melbourne, Parkville, VIC, 3010, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25117503

Citation

Rosty, Christophe, et al. "High Prevalence of Mismatch Repair Deficiency in Prostate Cancers Diagnosed in Mismatch Repair Gene Mutation Carriers From the Colon Cancer Family Registry." Familial Cancer, vol. 13, no. 4, 2014, pp. 573-82.
Rosty C, Walsh MD, Lindor NM, et al. High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the colon cancer family registry. Fam Cancer. 2014;13(4):573-82.
Rosty, C., Walsh, M. D., Lindor, N. M., Thibodeau, S. N., Mundt, E., Gallinger, S., ... Buchanan, D. D. (2014). High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the colon cancer family registry. Familial Cancer, 13(4), pp. 573-82. doi:10.1007/s10689-014-9744-1.
Rosty C, et al. High Prevalence of Mismatch Repair Deficiency in Prostate Cancers Diagnosed in Mismatch Repair Gene Mutation Carriers From the Colon Cancer Family Registry. Fam Cancer. 2014;13(4):573-82. PubMed PMID: 25117503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the colon cancer family registry. AU - Rosty,Christophe, AU - Walsh,Michael D, AU - Lindor,Noralane M, AU - Thibodeau,Stephen N, AU - Mundt,Erin, AU - Gallinger,Steven, AU - Aronson,Melyssa, AU - Pollett,Aaron, AU - Baron,John A, AU - Pearson,Sally, AU - Clendenning,Mark, AU - Walters,Rhiannon J, AU - Nagler,Belinda N, AU - Crawford,William J, AU - Young,Joanne P, AU - Winship,Ingrid, AU - Win,Aung Ko, AU - Hopper,John L, AU - Jenkins,Mark A, AU - Buchanan,Daniel D, PY - 2014/8/14/entrez PY - 2014/8/15/pubmed PY - 2015/7/22/medline SP - 573 EP - 82 JF - Familial cancer JO - Fam. Cancer VL - 13 IS - 4 N2 - 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. SN - 1573-7292 UR - https://www.unboundmedicine.com/medline/citation/25117503/High_prevalence_of_mismatch_repair_deficiency_in_prostate_cancers_diagnosed_in_mismatch_repair_gene_mutation_carriers_from_the_colon_cancer_family_registry_ L2 - https://doi.org/10.1007/s10689-014-9744-1 DB - PRIME DP - Unbound Medicine ER -