Mismatch repair status between primary colorectal tumor and metastatic tumor, a retrospective consistent study

Zheng Wang,Xiaoli Tang,Xiaoqing Wu,Daorong Wang,Meiyuan Yang

doi:10.1042/bsr20190730

Abstract

Objectives Mismatch repair (MMR) and Microsatellite instability (MSI) are critical when considering immunotherapy and chemotherapeutic drugs an option for patients with colorectal cancer (CRC). We investigated the consistence of MMR status as well as MSI between primary CRC and metastatic tumor to see if the expression of four MMR proteins and the status of MSI are congruent in primary tumor and metastatic tumor. With the results of the study and future more relevant studies, the sites of MMR testing may be more precise for individualized treatment.Study design Patients with clear diagnosis of sporadic CRC and distal organ metastasis were identified from a prospectively established database. The status of MMR and MSI was evaluated by immunohistochemistry (IHC) and Polymerase Chain Reaction (PCR) respectively of synchronously obtained tissue samples.Results Forty patients with complete clinical date were enrolled. For primary tumor, 36/40 samples were tested as MMR-proficient (pMMR) and 4 were MMR-deficient (dMMR). For metastatic samples, 30 samples were tested as pMMR while 10 samples were dMMR. Six out of forty patients were tested as inconsistent status of MMR and MSI. After statistical analysis, the expression status of MMR was not statistically significant between primary and metastatic tumors (P=0.1405, larger than 0.05).Conclusion Based on our samples, the status of MMR between primary CRC and metastatic tumor was consistent, thus test of MMR status can be performed at both sites. However, due to the limited samples enrolled in our study, the results should be interpreted carefully.

Highlights

Colorectal cancer (CRC) is one of the leading neoplasm around the world with more than 10000 new cases diagnosed per year in the United States [1]
Mutation of Mismatch Repair (MMR) gene usually results in loss of MMR protein and the tumor DNA becomes microsatellite instability-high (MSI/Microsatellite instability (MSI)-H) which leads to numerous mutations within the tumor cell [7]
Lymph node metastasis was found to be associated with inconsistent status of MMR

Summary

Introduction

Colorectal cancer (CRC) is one of the leading neoplasm around the world with more than 10000 new cases diagnosed per year in the United States [1]. 21% of CRC was metastatic and estimated 5-year survival for these patients was 13.9% [1,2]. The liver is the most common site for metastatic CRC and previously reported 3-year disease-free survival is approximately 14% after a hepatic resection [3]. Most of cases diagnosed with liver metastasis are unresectable and the first-line therapy for them was chemotherapy [4,5]. Mismatch Repair (MMR) Gene is defined as functional recognizing and repairing DNA damage during duplication [6]. CRC with MMR mutation was considered as a specific subtype of CRC which has distinct clinicopathologic features like proximal location, right-sided tumor, low metastasis and longer survival in early stage [8,9,10]

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