title: Expression status of wild-type HSP110 correlates with HSP110 T17 deletion size and patient prognosis in microsatellite-unstable colorectal cancer.
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.
authors.affiliation: 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.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Kyung-Ju
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Ye-Young
authors.initials: YY
authors.lastname: Rhee
authors.affiliation: Department of Biostatistics, SMG-SNU Boramae Medical Center, Seoul, South Korea.
authors.forename: Sohee
authors.initials: S
authors.lastname: Oh
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050957:HSP110 Heat-Shock Proteins