Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diseases of the Colon & Rectum
Published in: Diseases of the Colon & Rectum 1/2006

01-10-2006

Frequency of Immunohistochemical Loss of Mismatch Repair Protein in Double Primary Cancers of the Colorectum and Stomach in Japan

Authors: Tetsuji Hayashi, M.D., Masami Arai, M.D., Masashi Ueno, M.D., Hirokatsu Kinoshita, M.D., Yurika Tada, Koichi Koizumi, M.D., Yoshio Miki, M.D., Toshiharu Yamaguchi, M.D., Yo Kato, M.D., Joji Utsunomiya, M.D., Tetsuichiro Muto, M.D., Kenichi Sugihara, M.D.

Published in: Diseases of the Colon & Rectum | Special Issue 1/2006

Login to get access

Purpose

Colorectal cancer and gastric cancer are the two most commonly associated malignancies in Japan. We examined mismatch repair deficiency in the tumors of patients with primary colorectal and gastric cancers retrospectively.

Methods

In 103 cases and 102 healthy control subjects, surgical specimens of colorectal and gastric cancer underwent immunohistochemical analysis of mismatch repair proteins (hMLH1 and hMSH2) and microsatellite instability testing.

Results

Immunohistochemical and microsatellite instability testing produced similar results. High microsatellite instability in colorectal cancer was found in 23 of 103 cases (23 percent) with colorectal and gastric cancers, and in 8 of 102 healthy control subjects (8 percent). Twelve (12 percent) had mismatch repair deficiency in both colorectal and gastric cancers, and both tumors had loss of the same mismatch repair protein (hMLH1, n = 5; hMSH2, n = 7). They had the first cancer at a younger age, with a higher frequency of familial colorectal cancer than the others. Seventeen had mismatch repair deficiency in either tumor, which showed loss of expression of hMLH1. Multiple cancers and right-sided colon cancers developed more frequently in patients with mismatch repair deficiency.

Conclusions

Patients with both colorectal and gastric cancers are more likely to have phenotypic evidence of hereditary nonpolyposis colorectal cancer than patients with colorectal cancer only. Among patients with double tumors, 12 percent showed a common deficiency in the same mismatch repair protein in both tumors by immunohistochemistry, and they should undergo genetic counseling for germline mutational analysis. Immunohistochemistry was effective in detecting mismatch repair deficiency of colorectal and gastric cancer as well as microsatellite instability testing, and may be more practical to perform phenotypic analysis of tumors because of its cost-effectiveness.
Literature
1.
Tomoda, H, Taketomi, A, Baba, H,  et al. 1998Multiple primary colorectal and gastric carcinoma in JapanOncol Rep5147149PubMed
2.
Knudson, AG,Jr 1971Mutation and cancer: statistical study of retinoblastomaProc Natl Acad Sci USA68820823PubMedCrossRef
3.
Staebler, A, Lax, SF, Ellenson, LH 2000Altered expression of hMLH1 and hMSH2 protein in endometrial carcinomas with microsatellite instabilityHum Pathol31354358PubMedCrossRef
4.
Thibodeau, SN, French, AJ, Cunningham, JM,  et al. 1998Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1Cancer Res5817131718PubMed
5.
Thibodeau, SN, French, AJ, Roche, PC,  et al. 1996Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genesCancer Res5648364840PubMed
6.
Dietmaier, W, Wallinger, S, Bocker, T,  et al. 1997Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expressionCancer Res5747494756PubMed
7.
Dieumagard, B, Grandjouan, S, Sabourin, JC,  et al. 2000Extensive screening for hereditary non-polyposis colorectal cancerBr J Cancer82871880CrossRef
8.
Cawkwell, L, Gray, S, Murgatroyd, H,  et al. 1999Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repairGut45409415PubMedCrossRef
9.
Debniak, T, Kurzawski, G, Gorski, B,  et al. 2000Value of pedigree clinical data, immunohistochemistry and microsatellite instability analysis in reducing the cost of determining hMLH1 and hMSH2 gene mutations in patients with colorectal cancerEur J Cancer364954PubMedCrossRef
10.
Marcus, VA, Madlensky, L, Gryfe, R,  et al. 1999Immunohistochemistry for hMLH1 and hMSH2: a practical test for DNA mismatch repair-deficient tumorsAm J Surg Pathol2312481255PubMedCrossRef
11.
Ward, R, Meagher, A, Tomlinson, I,  et al. 2001Microsatellite instability and the clinicopathological features of sporadic colorectal cancerGut48821829PubMedCrossRef
12.
Vasen, HF, Watson, P, Mecklin, JP, Lynch, HT 1999New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCCGastroenterology11614531456PubMedCrossRef
13.
Watson, P, Lynch, HT 1993Extracolonic cancer in hereditary nonpolyposis colorectal cancerCancer71677685PubMedCrossRef
14.
Rodriguez-Bigas, MA, Boland, CR, Hamilton, SR,  et al. 1997A National Cancer Institute workshop on hereditary nonpolyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelinesJ Natl Cancer Inst8917581762PubMedCrossRef
15.
Hall, NR, Finan, PJ, Ward, B,  et al. 1994Genetic susceptibility to colorectal cancer in patients under 45 years of ageBr J Surg8414851489
16.
Plank, M, Rambech, E, Moslein, G, Muller, W, Olsson, H, Nilbert, M 2002High frequency of microsatellite instability and loss of mismatch-repair protein expression in patients with double primary tumors of the endometrium and colorectumCancer9425022510CrossRef
17.
Kane, MF, Loda, M, Gaida, GM,  et al. 1997Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell linesCancer Res57808811PubMed
18.
Lothe, RA, Peltomaki, P, Meling, GI,  et al. 1993Genomic instability in colorectal cancer: relationship to clinicopathological variables and family historyCancer Res5358495852PubMed
19.
Kim, H, Jen, J, Vogelstein, B, Hamilton, SR 1994Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequencesAm J Pathol145148156PubMed
20.
Herman, JG, Umar, A, Polyk, K,  et al. 1998Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinomaProc Natl Acad Sci USA9568706875PubMedCrossRef
Metadata
Title
Frequency of Immunohistochemical Loss of Mismatch Repair Protein in Double Primary Cancers of the Colorectum and Stomach in Japan
Authors
Tetsuji Hayashi, M.D.
Masami Arai, M.D.
Masashi Ueno, M.D.
Hirokatsu Kinoshita, M.D.
Yurika Tada
Koichi Koizumi, M.D.
Yoshio Miki, M.D.
Toshiharu Yamaguchi, M.D.
Yo Kato, M.D.
Joji Utsunomiya, M.D.
Tetsuichiro Muto, M.D.
Kenichi Sugihara, M.D.
Publication date
01-10-2006
Publisher
Springer-Verlag
Published in
Diseases of the Colon & Rectum / Issue Special Issue 1/2006
Print ISSN: 0012-3706
Electronic ISSN: 1530-0358
DOI
https://doi.org/10.1007/s10350-006-0722-z

Other articles of this Special Issue 1/2006

Diseases of the Colon & Rectum 1/2006 Go to the issue

OriginalPaper

Intersphincteric Resection in Patients with Very Low Rectal Cancer: A Review of the Japanese Experience

OriginalPaper

A New Concept for the Surgical Anatomy of Posterior Deep Complex Fistulas: The Posterior Deep Space and the Septum of the Ischiorectal Fossa

EditorialNotes

Editorial

OriginalPaper

Efficacy and Safety of Endoscopic Balloon Dilation for Crohn’s Strictures

OriginalPaper

The Risk of Multiple Primary Malignancies with Colorectal Carcinoma

Original Contributions

Who Can Get the Beneficial Effect from Lateral Lymph Node Dissection for Dukes C Rectal Carcinoma Below the Peritoneal Reflection?