Deletion in HSP110 T17: correlation with wild-type HSP110 expression and prognostic significance in microsatellite-unstable advanced gastric cancers

Abstract

Deletion of the HSP110 T₁₇ mononucleotide repeat has recently been identified as a prognostic marker that is correlated with wild-type HSP110 (HSP110wt) expression in microsatellite instability-high (MSI-H) colorectal cancers. The aim of this study was to assess the correlation between deletion of the HSP110 T₁₇ repeat and expression of HSP110wt using DNA testing and immunohistochemistry and to determine the prognostic implications of HSP110 T₁₇ deletion in MSI-H advanced gastric cancers (GCs). The status of HSP110wt expression was evaluated by immunohistochemistry using an HSP110wt-specific antibody in 142 MSI-H advanced GCs. The size of the HSP110 T₁₇ repeat deletion was analyzed in 96 MSI-H advanced GCs; deletions were divided into small (0-2base pairs) and large deletions (3-5base pairs). Low and high expressions of HSP110wt were detected in 38 (26.8%) and 104 (73.2%) of the 142 cases, respectively. The HSP110 T₁₇ deletion was observed in 45 (46.9%) of the 96 MSI-H GC samples. Tumors with high expression of HSP110wt showed a tendency to have small or no deletion of HSP110 T₁₇. In Kaplan-Meier survival analysis, tumors with a large HSP110 T₁₇ deletion were associated with favorable overall survival and disease-free survival compared with those with small/no deletion of HSP110 T₁₇. However, HSP110 T₁₇ deletion size was not an independent prognostic factor in multivariate analysis. In summary, deletion of the HSP110 T₁₇ repeat was frequently observed in MSI-H GCs, and HSP110 T₁₇ deletion size was inversely correlated with HSP110wt expression status. Large HSP110 T₁₇ was not a prognostic indicator in MSI-H GCs.

Keywords: Gastric cancer; HSP110; HSP110 T(17) deletion; Microsatellite instability; Prognosis.