Faculty Collaboration Database

Increased risk for hereditary nonpolyposis colorectal cancer-associated synchronous and metachronous malignancies in patients with microsatellite instability-positive endometrial carcinoma lacking MLH1 promoter methylation. Clin Cancer Res 2004 Jan 15;10(2):481-90

Date

02/05/2004

Pubmed ID

14760069

DOI

10.1158/1078-0432.ccr-1110-03

Scopus ID

2-s2.0-0842290011 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

PURPOSE: The aim of this study was to evaluate number and types of synchronous and metachronous malignancies in patients with endometrial carcinoma with and without microsatellite instability (MSI).

EXPERIMENTAL DESIGN: From a series of 413 endometrial cancer patients, we identified 94 patients with MSI-positive (MSI+) cancers and grouped them by tumor MLH1 promoter methylation status. These 94 patients were matched by year of surgery to 94 patients with MSI-negative (MSI-) endometrial cancers from the same series. Medical records were reviewed for clinicopathologic information including rates and types of synchronous and metachronous malignancies. Hereditary nonpolyposis colorectal cancer (HNPCC)-associated second and third cancers were analyzed for MSI and MSH2, MSH6, and MLH1 expression for comparison with the corresponding endometrial cancers.

RESULTS: The MSI+ and MSI- cohorts were similar with regard to age, race, grade, and histology. Twenty-eight MSI+ endometrial cancers (29.8%) were MLH1 unmethylated. Rates of synchronous and metachronous cancers were also similar in the MSI+ and MSI- groups at 20 and 23%, respectively. However, patients with MSI+ MLH1 unmethylated endometrial cancers had an excess of HNPCC-associated second and third cancers compared with those with MSI+ MLH1 methylated and MSI- endometrial cancers (18% versus 4.5%, P = 0.034, and 2.1%, P = 0.002). Six of seven second tumors from 5 patients with MSI+ MLH1 unmethylated endometrial cancers showed concordant MSI and mismatch repair protein expression status.

CONCLUSIONS: Our observation that patients with MSI-positive MLH1 unmethylated endometrial carcinoma are at increased risk for HNPCC-associated synchronous and metachronous malignancies suggests inherited cancer susceptibility. These patients and their families may warrant more intense cancer surveillance.

Author List

Buttin BM, Powell MA, Mutch DG, Rader JS, Herzog TJ, Gibb RK, Huettner P, Edmonston TB, Goodfellow PJ

Author

Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age of Onset
Aged
Cohort Studies
Colorectal Neoplasms, Hereditary Nonpolyposis
DNA
DNA Methylation
Endometrial Neoplasms
Female
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Microsatellite Repeats
Middle Aged
Models, Biological
Neoplasms, Second Primary
Promoter Regions, Genetic
Risk
Tamoxifen