Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome

Abstract Urothelial carcinoma of the upper urinary tract is relatively uncommon but may develop as a manifestation of the hereditary nonpolyposis colorectal cancer syndrome (HNPCC), which is characterized by mutations in a number of DNA mismatch repair genes and detectable as microsatellite instability or loss of the respective protein by immunostaining. No well-established screening test is available for urothelial carcinomas of the upper urinary tract, and little is known of the clinical impact of screening for HNPCC in patients with upper urinary tract cancer. We describe herein a patient with a urothelial carcinoma of the ureter and a strongly positive history of cancer, who was subsequently found to have HNPCC. Our findings reinforce the importance of obtaining a comprehensive history of cancer in patients with urothelial carcinoma of the renal pelvis and ureter. Subsequent identification of individuals with HNPCC enables the patient and at-risk relatives to benefit from targeted surveillance and management programs.

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Missense Mismatch Repair Gene Alterations, Microsatellite Instability, and Hereditary Nonpolyposis Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.14.3178 ◽

2002 ◽

Vol 20 (14) ◽

pp. 3178-3179 ◽

Cited By ~ 10

Author(s):

Wade S. Samowitz ◽

Martha L. Slattery ◽

Emilio Porfiri ◽

Mario Scartozzi ◽

Andrea Piga ◽

...

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Mismatch Repair ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Mismatch Repair Gene ◽

Repair Gene ◽

Hereditary Nonpolyposis ◽

Gene Alterations

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Immunohistochemistry Identifies Carriers of Mismatch Repair Gene Defects Causing Hereditary Nonpolyposis Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.180 ◽

2005 ◽

Vol 23 (21) ◽

pp. 4705-4712 ◽

Cited By ~ 24

Author(s):

Astrid T. Stormorken ◽

Inger Marie Bowitz-Lothe ◽

Tove Norèn ◽

Elin Kure ◽

Steinar Aase ◽

...

Keyword(s):

Colorectal Cancer ◽

Mismatch Repair ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Mismatch Repair Gene ◽

Repair Gene ◽

Predictive Values ◽

Blood Samples ◽

Bethesda Criteria ◽

Amsterdam Criteria ◽

Hereditary Nonpolyposis

Purpose Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by mutations in mismatch repair (MMR) genes. The aim of this study was to validate immunohistochemistry and family history as prescreening tools to predict germline mutations in MLH1, MSH2, and MSH6. Patients and Methods Pedigrees from 250 families were extended, cancer diagnoses were verified, and families were classified according to the Amsterdam and the Bethesda criteria. Tumor specimens were examined with immunohistochemistry for the presence of MLH1, MSH2, and MSH6 proteins. Mutation analyses were performed in blood samples from the same patients. Results Blood samples from affected index persons in 181 families and tumor specimens from 127 of the affected index persons were obtained. Thirty tumors lacked one or more gene products. Sensitivity of immunohistochemistry to detect mutation carriers was 100%, specificity was 82%, and positive predictive value was 85%. Sensitivities, specificities, and positive predictive values for the Amsterdam criteria were 82%, 8%, and 45%, respectively, and for the Bethesda criteria were 100%, 0%, and 48%, respectively. Distribution of mutations was MLH1 = 4, MSH2 = 11, and MSH6 = 4. Conclusion Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations.

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Comprehensive Molecular Analysis of Mismatch Repair Gene Defects in Suspected Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) Cases

Cancer Research ◽

10.1158/0008-5472.can-09-0358 ◽

2009 ◽

Vol 69 (17) ◽

pp. 7053-7061 ◽

Cited By ~ 30

Author(s):

James Mueller ◽

Isabella Gazzoli ◽

Prathap Bandipalliam ◽

Judy E. Garber ◽

Sapna Syngal ◽

...

Keyword(s):

Colorectal Cancer ◽

Lynch Syndrome ◽

Mismatch Repair ◽

Molecular Analysis ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Mismatch Repair Gene ◽

Repair Gene ◽

Hereditary Nonpolyposis ◽

Gene Defects

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Molecular Analysis of Colorectal Cancer Tumors from Patients with Mismatch Repair–Proficient Hereditary Nonpolyposis Colorectal Cancer Suggests Novel Carcinogenic Pathways

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-06-2996 ◽

2007 ◽

Vol 13 (19) ◽

pp. 5729-5735 ◽

Cited By ~ 39

Author(s):

Ana Sánchez-de-Abajo ◽

Miguel de la Hoya ◽

Marjo van Puijenbroek ◽

Alicia Tosar ◽

J.A. López-Asenjo ◽

...

Keyword(s):

Colorectal Cancer ◽

Mismatch Repair ◽

Molecular Analysis ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Hereditary Nonpolyposis

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MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1722106115 ◽

2018 ◽

Vol 115 (11) ◽

pp. 2806-2811 ◽

Cited By ~ 3

Author(s):

David W. Brammer ◽

Patrick J. Gillespie ◽

Mei Tian ◽

Daniel Young ◽

Muthuswamy Raveendran ◽

...

Keyword(s):

Colorectal Cancer ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Rhesus Macaques ◽

Pedigree Analysis ◽

Hepatic Flexure ◽

Cancer Center ◽

Cancer Syndrome ◽

University Of Texas ◽

Hereditary Nonpolyposis ◽

Md Anderson

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques (Macaca mulatta) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoroacetate ([18F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [18F]fluorothymidine ([18F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1-rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.

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Advanced Colon Cancer Before the Age of 20 Years: A Case for Extension of the Current Colonscopy Surveillance Guidelines in Hereditary Nonpolyposis Colorectal Cancer Syndrome

Canadian Journal of Gastroenterology ◽

10.1155/2004/746174 ◽

2004 ◽

Vol 18 (5) ◽

pp. 319-320 ◽

Cited By ~ 1

Author(s):

Victor K Wong ◽

Eric M Yoshida ◽

Anthony G Ryan ◽

Stephen GF Ho ◽

Baljinder Salh

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Hereditary Nonpolyposis Colorectal Cancer ◽

Pelvic Mass ◽

Cancer Syndrome ◽

Advanced Colon Cancer ◽

Hereditary Nonpolyposis ◽

History Of ◽

Current Guidelines ◽

Colorectal Adenocarcinomas

BACKGROUND:Hereditary nonpolyposis colorectal cancer (HNPCC) currently accounts for between 2% to 6% of all colorectal adenocarcinomas. Controversies exist regarding the current guidelines for colonoscopic screening for colon cancer.CASE REPORT:A case of colon cancer in a young Japanese man with a family history of colon cancer that did not meet the criteria for HNPCC is reported. A malignant pelvic mass discovered shortly before his 20th birthday prompted a colonoscopy. The findings at colonscopy determined that the patient and his family fulfilled the criteria of HNPCC.CONCLUSION:Before finding a pelvic mass metastatic from adenocarcinoma of the ascending colon, this patient was clearly outside of the current guidelines for HNPCC screening. It is suggested that in similar patients, even if they do not fulfill all the criteria for HNPCC, it would be appropriate to consider screening well before the recommended lower age.

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