Dominant high expression of wild‐type HSP110 defines a poor prognostic subgroup of colorectal carcinomas with microsatellite instability: a whole‐section immunohistochemical analysis

Abstract

The aim of this study is to establish heat shock protein 110 (HSP110) as a prognostic biomarker of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) by considering the intratumoral heterogeneity of HSP110 expression. We performed whole-section immunohistochemistry (IHC) for wild-type HSP110 (HSP110wt) in 164 MSI-H CRCs. The intensity of the HSP110wt expression in tumor cells was semiquantitatively scored (0/1/2/3), and the HSP110wt expression status of each tumor was classified as low or high using the following four scoring criteria: H-score, dominant intensity score, lowest intensity score, and highest intensity score. Among the four criteria, only the dominant intensity score-based dichotomous classification of HSP110wt expression was significantly associated with a difference in disease-free survival (log-rank p = 0.035) in 164 MSI-H CRCs. The HSP110wt-low MSI-H CRCs were significantly correlated with larger deletions in the HSP110 T mononucleotide repeat (≥4 bp; p < 0.001). In conclusion, the dominant intensity score-based assessment of HSP110wt IHC can be a simple and useful method for the prognostic stratification of MSI-H CRCs. It is expected that HSP110wt IHC may be used to identify a subgroup of MSI-H CRCs with poor prognosis and/or candidates for further treatment, such as immunotherapy using immune checkpoint inhibitors in MSI-H CRCs.

HSP105 expression in oral squamous cell carcinoma: Correlation with clinicopathological features and outcomes

“…However, Kawai et al, 21 showed that a high HSP105 score was significantly associated with a favorable prognosis in patients with urinary bladder cancer treated with radical cystectomy. In line with our study, the poor prognosis was also associated with HSP 105 overexpression in myeloblastic syndromes, 8 in colorectal carcinomas 22 and in gastric cancer. 23 Different findings suggest that HSP105 may function differently in bladder cancer or elsewhere, compared to oral squamous cell carcinoma and squamous cell carcinoma of the lung.…”

The Prognostic Significance of Hsp70 in Patients with Colorectal Cancer Patients: A PRISMA-Compliant Meta-Analysis

“…Another 42 records had insufficient data for HR calculation. Finally, 11 articles with 2269 patients were used [21][22][23][25][26][27][28][29][30][31][32]. The 11 articles had a sample size of 167 to 256 (average 206) (Table 1).…”

“…Studies have shown that Hsp70 expression is upregulated in various carcinoma tissues and could be a potential biomarker [7]. Besides, previous studies have reported that Hsp70 overexpression is associated with poor survival in some cancers, including breast carcinoma [8][9][10], esophageal adenocarcinoma [11], non-small-cell lung cancer [12], prostate cancer [13,14], gastric cancer [15,16], leukemia [17], hepatocellular carcinoma [18,19], pancreatic cancer [20], and colon cancer [21][22][23]. However, no study has reported the relationship between the Hsp70 expression level and prognosis of colorectal cancer patients.…”

Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer

“…Hwang et al described increased HSP110 expression in cell lines from metastatic compared to non-metastatic CRC [62]. Kim et al found better disease free survival in patients with microsatellite-instable (MMR deficient) CRC characterized by HSP110 downregulation; explaining this by deletion of the HSP110 T17 gene, which is associated with genomic instability in MMR deficient tumors [67,68]. The same was described in gastric cancer [69].…”