Immunogenic hsp-70 is overexpressed in colorectal cancers with high-degree microsatellite instability.
OBJECTIVE
Colorectal cancers that display high-degree mi-crosatellite instability are associated with an improved prognosis and evidence of an activated host immune response. Molecular analyses have suggested that heat shock proteins, a family of proteins that have key immunologic functions, are upregulated in these cancers. We aimed to explore the expression of heat shock proteins 70 and 110 and their relationship to microsatellite instability, survival, and other clinicopathologic parameters.


METHODS
Twenty-six colorectal cancers that displayed microsatellite instability were matched by age, stage, and site in the colorectum to 26 microsatellite-stable cancers. Immunohistochemistry was used to detect expression of both markers.


RESULTS
The microsatellite-unstable group showed significantly higher expression of heat shock protein 70 than the microsatellite-stable group (P = 0.006), and patients undergoing curative resections for unstable cancers had improved prognosis compared with their stable counterparts (P = 0.026). Significantly, in a multivariate survival analysis, low or absent heat shock protein 70 expression was independently associated with a poor outcome (P = 0.001).


CONCLUSIONS
Heat shock protein 70 has known functions that promote antitumor immune responses. Its overexpression in colorectal cancers with microsatellite instability may be pivotal to explaining these tumors' enhanced immunogenicity and improved prognosis.
Banerjea
Ayan
A
Centre for Academic Surgery, Barts and the London Queen Mary School of Medicine and Dentistry, The Royal London Hospital, Whitechapel, London, United Kingdom, a.banerjea@qmul.ac.uk.
Feakins
Roger M
RM
Nickols
Carole D
CD
Phillips
Simon M
SM
Powar
Michael P
MP
Bustin
Stephen A
SA
Dorudi
Sina
S
D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D042822:Genomic Instability; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis
D018840:HSP70 Heat-Shock Proteins