Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan 3:12:769281.
doi: 10.3389/fgene.2021.769281. eCollection 2021.

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

Gaelle Tachon  1   2   3 , Arnaud Chong-Si-Tsaon  1   3   4 , Thierry Lecomte  5   6 , Audelaure Junca  4 , Éric Frouin  1   4 , Elodie Miquelestorena-Standley  7 , Julie Godet  4 , Camille Evrard  8 , Violaine Randrian  1   9 , Romain Chautard  6 , Marie-Luce Auriault  10 , Valérie Moulin  11 , Serge Guyetant  7 , Gaelle Fromont  7 , Lucie Karayan-Tapon  1   2   3 , David Tougeron  1   9
Affiliations

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

Gaelle Tachon et al. Front Genet. .

Abstract

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 HSP110 T 17 microsatellite has been reported to be more monomorphic than the common markers used for MSI determination. Large deletion of HSP110 T 17 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 (n = 381). IHC of the 4 MMR proteins was carried out. HSP110 expression was carried out by IHC (n = 343), and the size of HSP110 T 17 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 HSP110 T 17 deletion. Only 5.8% of MSI CRCs had no HSP110 T 17 deletion (n = 19/327). HSP110 T 17 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 HSP110 T 17 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, HSP110 T17 is an interesting marker, which may be combined with the other pentaplex markers to identify discordant cases between MMR IHC and MSI.

Keywords: HSP110; Lynch syndrome; adjuvant chemotherapy; biomarker; colorectal cancer; deficient mismatch repair; microsatellite instability.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Molecular determination of HSP110 T 17 deletion. (A) Homozygous T 16 /T 16 and HSP110 T 17 /T 17 and heterozygous T 16 /T 17 HSP110 profiles from MSS CRC tissues. Peak of 147bp is indicated in black. (B) MSI tumor with a large deletion (−5bp) of HSP110 T 17 . (C) MSI tumor with a small deletion (−2bp) of HSP110 T 17 . The gray frame is the polymorphic area. Arrows indicate the size of the deleted transcript. (D) Distribution of samples according to the size of HSP110 T 17 deletion.
FIGURE 2
FIGURE 2
Distribution of the size of HSP110 T17 deletion according to HSP110 immunohistochemistry.
FIGURE 3
FIGURE 3
Time to recurrence. Kaplan–Meier curves showing the time to recurrence in patients with stage II or III MSI CRC according to (A) size of HSP110 T 17 deletion and (B) HSP110 expression and time to recurrence in patients with stage II or III MSI CRC who received adjuvant chemotherapy according to (C) size of HSP110 T 17 deletion and (D) HSP110 expression.
See this image and copyright information in PMC

References

    1. André T., Shiu K.-K., Kim T. W., Jensen B. V., Jensen L. H., Punt C., et al. (2020). Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N. Engl. J. Med. 383, 2207–2218. 10.1056/NEJMoa2017699 - DOI - PubMed
    1. Augustus G. J., Ellis N. A. (2018). Colorectal Cancer Disparity in African Americans. Am. J. Pathol. 188, 291–303. 10.1016/j.ajpath.2017.07.023 - DOI - PMC - PubMed
    1. Baudrin L. G., Deleuze J.-F., How-Kit A. (2018a). Molecular and Computational Methods for the Detection of Microsatellite Instability in Cancer. Front. Oncol. 8, 621. 10.3389/fonc.2018.00621 - DOI - PMC - PubMed
    1. Baudrin L. G., Duval A., Daunay A., Buhard O., Bui H., Deleuze J.-F., et al. (2018b). Improved Microsatellite Instability Detection and Identification by Nuclease-Assisted Microsatellite Instability Enrichment Using HSP110 T17. Clin. Chem. 64, 1252–1253. 10.1373/clinchem.2018.287490 - DOI - PubMed
    1. Berardinelli G. N., Scapulatempo-Neto C., Durães R., Antônio de Oliveira M., Guimarães D., Reis R. M. (2018). Advantage of HSP110 (T17) Marker Inclusion for Microsatellite Instability (MSI) Detection in Colorectal Cancer Patients. Oncotarget 9, 28691–28701. 10.18632/oncotarget.25611 - DOI - PMC - PubMed