J Pathol Transl Med.  2017 Mar;51(2):129-136. 10.4132/jptm.2016.12.09.

Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry

Affiliations
  • 1Department of Pathology, Korea University Anam Hospital, Seoul, Korea. chaeys21@korea.ac.kr

Abstract

BACKGROUND
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Approximately 10%-15% of the CRC cases have defective DNA mismatch repair (MMR) genes. Although the high level of microsatellite instability status is a predictor of favorable outcome in primary CRC, little is known about its frequency and importance in secondary CRC. Immunohistochemical staining (IHC) for MMR proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has emerged as a useful technique to complement polymerase chain reaction (PCR) analyses.
METHODS
In this study, comparison between the MMR system of primary CRCs and paired liver and lung metastatic lesions was done using IHC and the correlation with clinical outcomes was also examined.
RESULTS
Based on IHC, 7/61 primary tumors (11.4%) showed deficient MMR systems, while 13/61 secondary tumors (21.3%) showed deficiencies. In total, 44 cases showed proficient expression in both the primary and metastatic lesions. Three cases showed deficiencies in both the primary and paired metastatic lesions. In 10 cases, proficient expression was found only in the primary lesions, and not in the corresponding metastatic lesions. In four cases, proficient expression was detected in the secondary tumor, but not in the primary tumor.
CONCLUSIONS
Although each IHC result and the likely defective genes were not exactly matched between the primary and the metastatic tumors, identical results for primary and metastatic lesions were obtained in 77% of the cases (47/61). These data are in agreement with the previous microsatellite detection studies that used PCR and IHC.

Keyword

Colorectal neoplasms; DNA mismatch repair; Microsatellite instability; Immunohistochemistry

Figure

  • Fig. 1. Overall survival for the entire cohort (proficient mismatch repair [MMR] and deficient MMR patients).

  • Fig. 2. Immunohistochemical analyses of primary colorectal cancer for MLH1 (A), MSH2 (B), MSH6 (C), and PMS2 (D). Immunohistochemical analyses of metastatic colorectal cancer for MLH1 (E), MSH2 (F), MSH6 (G), and PMS2 (H). A lack of staining for MSH2 and MSH6 indicates a primary defect in MSH2, with a secondary loss of MSH6 expression.


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