The clinical importance and prognostic implications of microsatellite instability in sporadic cancer

doi:10.1053/ejso.2002.1399

European Journal of Surgical Oncology (EJSO)

Volume 29, Issue 3, April 2003, Pages 201-212

https://doi.org/10.1053/ejso.2002.1399 Get rights and content

Abstract

Aims: The genetic abnormality known as microsatellite instability (MSI), first identified in colorectal cancer in 1993, has subsequently been recognised in other malignancies. These cancers are caused by a defect in the nuclear mismatch repair system, allowing mutations to accumulate with every cellular division. Hereditary Non Polyposis Colon Cancers (HNPCC) and associated malignancies demonstrating MSI have a unique histological appearance, improved prognosis and altered response to chemotherapy and radiotherapy. This review examines the incidence of MSI and its clinical significance in commonly occurring solid malignancies.

Method: A medline based literature search was performed using the key words ‘Microsatellite Instability’ and the name of the specific malignancy being investigated. Additional original papers were obtained from citations in those articles identified in the original medline search.

Results: MSI has been detected in many solid malignancies although the definition of instability applied has been variable. It is most commonly found in sporadic malignancies that also occur in the HNPCC syndrome such as colorectal, stomach, endometrial and ovarian cancer. MSI may impart a favorable prognosis in colorectal, gastric, pancreatic and probably oesophageal cancers but a poor prognosis in non small cell lung cancer. In clinical studies colorectal cancers demonstrating MSI respond better to chemotherapy while in vitro studies using MSI positive cell lines show resistance to radiotherapy and chemotherapy.

Conclusion: MSI may be a useful genetic marker in prognosis and could be an influential factor in deciding treatment options. However, in many cancers its significance remains unclear and more evaluation is required.

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^f1: Correspondence to: Professor P. B. Boulos, Department of Surgery, Royal Free and University College Medical School, University College London, 2nd Floor, Charles Bell House, 67–73 Riding House Street, London, WIW 7EJ, UK. Tel: +442076799317; Fax: +442076799317; E-mail:[email protected]

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Review ArticleThe clinical importance and prognostic implications of microsatellite instability in sporadic cancer

Abstract

A genetic model for colorectal tumorigenesis

Cell

Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis

Nature

Microsatellite instability in cancer of the proximal colon

Science

Clues to the pathogenesis of familial colorectal cancer

Science

A National Cancer Institute Workshop on Microsatellite Instability for cancer detec-tion and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer

Cancer Res

Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability

Science

Microsatellite instability in the insulin-like growth factor II receptor gene in gastrointestinal tumours

Nat Genet

Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal tumors

Cancer Res

Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype

Science

Widespread microsatellite instability occurs infrequently in adenocarcinoma of the gastric cardia

Oncogene

Alternative genetic pathways in colorectal carcinogenesis

Proc Natl Acad Sci USA

Does MSI-low exist?

J Pathol

Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways

J Clin Pathol

Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations

Am J Hum Genet

Application of the National Cancer Institute international criteria for determination of micro- satellite instability in ovarian cancer

Cancer Res

The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer

Gastroenterology

Molecular screening for hereditary nonpolyposis colorectal cancer: a prospective, population-based study

J Clin Oncol

Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome

Int J Cancer

The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer

Am J Med

The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC)

Dis Colon Rectum

Genetic testing is important in families with a history suggestive of hereditary non-polyposis colorectal cancer even if the Amsterdam criteria are not fulfilled

Br J Surg

New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC

Gastroenterology

Association of sebaceous gland tumors and internal malignancy: the Muir–Torre syndrome

Am J Med

Muir–Torre syndrome in several members of a family with a variant of the Cancer Family Syndrome

Br J Dermatol

Colorectal cancer and the Muir–Torre syndrome in a Gypsy family: a review

Am J Gastroenterol

Structure of the human MSH2 locus and analysis of two Muir–Torre kindreds for msh2 mutations

Genomics

Genetic linkage in Muir–Torre syndrome to the same chromosomal region as cancer family syndrome

Eur J Cancer

The genetic basis of Muir–Torre syndrome includes the hMLH1 locus

Am J Hum Genet

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Cancer Res

The molecular basis of Turcot's syndrome

N Engl J Med

The hPMS2 exon 5 mutation and malignant glioma. Case report

J Neurosurg

Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome

Genes Chromosomes Cancer

Brain tumor-polyposis syndrome: two genetic diseases?

J Clin Oncol

Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients

Nat Med

Microsatellite instability and the role of hMSH2 in sporadic colorectalcancer

Oncogene

Colorectal carcinoma survival among hereditary nonpolyposis colorectal carcinoma family members

Cancer

Varying features of early age-of-onset ‘sporadic’ and hereditary nonpolyposis colorectal cancer patients

Dis Colon Rectum

Survival analysis in families affected by hereditary non-polyposis colorectal cancer

Int J Cancer

Pathology of hereditary nonpolyposis colorectal cancer

Ann N Y Acad Sci

Review Article
The clinical importance and prognostic implications of microsatellite instability in sporadic cancer