AUTHOR=Tachon Gaelle , Chong-Si-Tsaon Arnaud , Lecomte Thierry , Junca Audelaure , Frouin Éric , Miquelestorena-Standley Elodie , Godet Julie , Evrard Camille , Randrian Violaine , Chautard Romain , Auriault Marie-Luce , Moulin Valérie , Guyetant Serge , Fromont Gaelle , Karayan-Tapon Lucie , Tougeron David 

TITLE=HSP110 as a Diagnostic but Not a Prognostic Biomarker in Colorectal Cancer With Microsatellite Instability

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.769281

DOI=10.3389/fgene.2021.769281

ISSN=1664-8021

ABSTRACT=<p>Determination of microsatellite instability (MSI) using molecular test and deficient mismatch repair (dMMR) using immunohistochemistry (IHC) has major implications on colorectal cancer (CRC) management. The <italic>HSP110 T</italic><sub><italic>17</italic></sub> microsatellite has been reported to be more monomorphic than the common markers used for MSI determination. Large deletion of <italic>HSP110 T</italic><sub><italic>17</italic></sub> has been associated with efficacy of adjuvant chemotherapy in dMMR/MSI CRCs. The aim of this study was to evaluate the interest of HSP110 deletion/expression as a diagnostic tool of dMMR/MSI CRCs and a predictive tool of adjuvant chemotherapy efficacy. All patients with MSI CRC classified by molecular testing were included in this multicenter prospective cohort (<italic>n</italic> = 381). IHC of the 4 MMR proteins was carried out. HSP110 expression was carried out by IHC (<italic>n</italic> = 343), and the size of <italic>HSP110 T</italic><sub><italic>17</italic></sub> deletion was determined by PCR (n = 327). In the 293 MSI CRCs with both tests, a strong correlation was found between the expression of HSP110 protein and the size of <italic>HSP110 T</italic><sub><italic>17</italic></sub> deletion. Only 5.8% of MSI CRCs had no <italic>HSP110 T</italic><sub><italic>17</italic></sub> deletion (<italic>n</italic> = 19/327). <italic>HSP110 T</italic><sub><italic>17</italic></sub> deletion helped to re-classify 4 of the 9 pMMR/MSI discordance cases as pMMR/MSS cases. We did not observe any correlation between HSP110 expression or <italic>HSP110 T</italic><sub><italic>17</italic></sub> deletion size with time to recurrence in patients with stage II and III CRC, treated with or without adjuvant chemotherapy. HSP110 is neither a robust prognosis marker nor a predictor tool of adjuvant chemotherapy efficacy in dMMR/MSI CRC. However, <italic>HSP110 T<sub>17</sub></italic> is an interesting marker, which may be combined with the other pentaplex markers to identify discordant cases between MMR IHC and MSI.</p>