The incidence of mismatch repair gene defects in colorectal liver metastases

Abstract

Abstract. Knowledge of the molecular biology of primary colorectal cancer (CRC) has improved in recent years, and one reason for this is the identification of microsatellite instability (MSI), which occurs in up to 15% of sporadic CRC. However, less is known regarding the processes involved in colorectal liver metastases (CRLM). Increasing numbers of patients with CRLM are suitable for curative resection, so the identification of molecular markers may improve patient selection. The aim of the present study was to characterise the incidence of MSI in resected CRLM. Fifty-one sequentially resected CRLM specimens were selected. Clinicopathologic data was collated and immunohistochemistry for MLH1 and MSH2 was performed on paraffin sections of the CRLM specimens. The association between abnormal staining and the clinicopathological data was examined. The median age of the subjects in the current study was 65 years, the average number of CRLM was 2 and the median overall survival time was 42.1 months post liver resection. None of the 50 resected specimens demonstrated abnormal staining for MLH1 or MSH2. Compared with the previously reported incidence of MSI in primary CRC, the low incidence of MSI in the current cohort of CRLM precludes its use as a marker for use in making clinical decisions regarding this condition.

The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

“…The significance of dMMR phenotype in Stage IV disease is still uncertain [28,38]. In this study, dMMR tumors were inversely associated with liver-only metastases (Table 5), a finding that has been reported in some studies [39][40][41]. Catalano et al [42] found non-mucinous tumors to be associated with more liver metastasis compared to mucinous counterpart and most dMMR tumors are phenotypically mucinous.…”

Biomarkers in colorectal liver metastases

“…Vauthey et al 25 193 1⋅0 Karagkounis et al 26 202 2⋅0 Teng et al 27 292 2⋅1 Schirripa et al 28 309 3⋅9 Løes et al 29 164 6⋅1 MSI-H Umeda et al 30 100 0 Alvarado-Bachmann et al 31 33 0 Rosty et al 32 56 2 Haddad et al 33 190 2⋅7 Mackay et al 34 29…”

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver metastases of colorectal cancer

“…In LM-CRC the incidence of MMR deficiency is low, 32 and it may therefore be expected that LM-CRC poorly respond to immune checkpoint inhibitors. Nevertheless, these tumors contain immune infiltrates, and increased numbers of tumor-infiltrating CD8 + T cells are positively associated with overall survival and response to chemotherapy, 33 , 34 indicating that intra-tumoral T cell immunity is an important determinant of LM-CRC progression.…”