Cancer Res Treat.  2012 Sep;44(3):179-186.

Clinico-pathologic Parameters for Prediction of Microsatellite Instability in Colorectal Cancer

Affiliations
  • 1Department of Pathology, Kosin University College of Medicine, Busan, Korea.
  • 2Department of Surgery, Dream Hospital, Daegu, Korea.
  • 3Department of Pathology, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea.
  • 4Department of Medical Statistics, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea.
  • 5Department of Laboratory Medicine, Daegu Catholic University Medical Center, Catholic University of Daegu School of Medicine, Daegu, Korea. chjeon@cu.ac.kr

Abstract

PURPOSE
Although the incidence of microsatellite instability (MSI) accounts for 10-15% of cases of colorectal cancer, its clinical application for all colorectal cancers has widened. We attempted to identify clinical and pathological parameters that may be helpful in selection of patients with MSI-high (MSI-H).
MATERIALS AND METHODS
A total of 120 resected colorectal cancers were enrolled retrospectively for this MSI study. Polymerase chain reaction (PCR) and denaturing high performance liquid chromatography and/or real time PCR methods with five markers and immunohistochemistry (IHC) for MLH1 and MSH2 were performed for analysis of cancer and blood specimens. Clinico-pathologic parameters, including IHC, were investigated in order to determine their usefulness as predictive factors of MSI.
RESULTS
Among 120 cases of colorectal cancer, MSI was observed in 15 cases (12.5%), including 11 cases of MSI-H and four cases of MSI-low. Patients with MSI were younger, less than 50 years old, had a family history of cancer, Rt. sided colon cancer and/or synchronous multiple colorectal cancer, mucinous histologic type, and serum carcinoembryonic antigen group in the normal range. Results of multivariate analysis showed Bethesda guidelines, Rt. sided and/or synchronous multiple colorectal cancer, and negative expression of IHC for MLH1, which was consistently associated with MSI-H. MSI-H colorectal tumors have met at least one of these three parameters and their sensitivity and specificity were 100% and 72.5%, respectively.
CONCLUSION
Bethesda guidelines, tumor location, and negative expression of MLH1 protein are important parameters for selection of patients with colorectal cancers for MSI testing. MSI testing is recommended for patients showing any of these three parameters.

Keyword

Colorectal neoplasms; Microsatellite instability; Chromatography; MLH1 protein

MeSH Terms

Carcinoembryonic Antigen
Chromatography
Chromatography, Liquid
Colonic Neoplasms
Colorectal Neoplasms
Humans
Immunohistochemistry
Incidence
Microsatellite Instability
Microsatellite Repeats
Mucins
Multivariate Analysis
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Reference Values
Retrospective Studies
Sensitivity and Specificity
Succinimides
Carcinoembryonic Antigen
Mucins
Succinimides

Figure

  • Fig. 1 Microsatellite analysis of NR21 (A), NR22 (B), and NR24 (C) by denaturing high performance liquid chromatography. Microsatellite instability positive specimen (P) showed double peak of chromatogram compared with single peak of control specimen (C).

  • Fig. 2 Microsatellite analysis of BAT26 using Light Cycler. BAT26 positive specimens showed shifted melting peaks due to shortening of poly A, as indicated by "P".


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