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Mod Pathol. 2014 Mar;27(3):443-53. doi: 10.1038/modpathol.2013.160. Epub 2013 Sep 13.

Expression status of wild-type HSP110 correlates with HSP110 T17 deletion size and patient prognosis in microsatellite-unstable colorectal cancer.

Author information

1
1] Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea [2] Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, South Korea.
2
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
3
Department of Biostatistics, SMG-SNU Boramae Medical Center, Seoul, South Korea.
4
Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
5
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea.
6
1] Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea [2] Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

Abstract

It has been recently suggested that the expression levels of mutant HSP110 could be a prognostic marker in colorectal cancer with a high level of microsatellite instability (MSI-H). The aim of our study was to validate the prognostic significance of HSP110 mutation using immunohistochemistry and DNA testing in MSI-H colorectal cancer. Wild-type HSP110 (HSP110wt)-specific immunohistochemistry was performed in 168 MSI-H colorectal cancer tissues, and their expression levels were evaluated using a four-tier scoring system (0/1+/2+/3+). Of these tissues, 167 cases were analyzed for HSP110 T17 deletion. Associations with clinicopathological, molecular and survival parameters were statistically analyzed. The low-level expression of HSP110wt (0/1+) was observed in 40 MSI-H colorectal cancers (24%) and was significantly related to large HSP110 T17 deletions (≥ 4 bp, P<0.001). In survival analysis, patients with low HSP110wt expression (0/1+) showed better disease-free survival compared with those with high expression (2+/3+; P=0.005). This significance in survival difference was maintained in patients with 5-fluorouracil-based chemotherapy-treated tumors (P=0.024) and in those with stage III/IV tumors (P=0.032). Multivariate analysis confirmed the role of HSP110wt expression as an independent prognostic factor (P=0.016, hazard ratio=4.32). In MSI-H colorectal cancer, a low expression of HSP110wt is associated with large HSP110 T17 deletions and better clinical outcome. Immunohistochemistry of HSP110wt can be a simple and valuable tool for the prognostic and therapeutic stratification of patients with MSI-H colorectal cancer.

PMID:
24030751
DOI:
10.1038/modpathol.2013.160
[Indexed for MEDLINE]
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