Large bowel carcinogenesis involves accumulation of genetic alterations leading to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It is pertinent to elucidate the molecular changes occurring in the pre-neoplastic lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps), many of which are molecular chaperones, are implicated in carcinogenesis, and their variations with tumor progression encourage their study as biomarkers. There are many reports on Hsps and cancer but none to our knowledge on their systematic quantification in pre-neoplastic lesions of the large bowel. We performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, and Hsp90 in biopsies of large bowel tubular adenomas with moderate grade of dysplasia and compared to normal mucosa and adenocarcinoma with a moderate grade of differentiation (G2). A significant elevation of Hsp10 and Hsp60 only, i.e., in the absence of elevation of Hsp70 or Hsp90, in both epithelium and lamina propria was found in tubular adenoma by comparison with normal mucosa. In contrast, adenocarcinoma was characterized by the highest levels of Hsp10 and Hsp60 in epithelium and lamina propria, accompanied by the highest levels of Hsp70 only in epithelium and of Hsp90 only in lamina propria, by comparison with normal and tubular adenoma counterparts. Hsp10 and Hsp60 are promising biomarkers for early diagnosis of tubular adenoma and for its differentiation from more advanced malignant lesions. Hsp10 and Hsp60 may be implicated in carcinogenesis from its very early steps and, thus, are potentially convenient targets for therapy.
Hsps Chaperone Large bowel Dysplasia Tubular adenoma Biomarker
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A.J.L.M. and E.C. de M. were partially supported by IMET; A.J.L.M. and F.C. were partially supported by IEMEST. This work was done under the umbrella of the agreement between the Euro-Mediterranean Institute of Science and Technology (IEMEST, Italy) and the Institute of Marine and Environmental Technology (IMET, USA) signed in March 2012 (this is IMET contribution number IMET 16-176).
Compliance with ethical standards
The work was partially supported by the Euro-Mediterranean Institute of Science and Technology (IEMEST) and the University of Palermo. In this work were used instruments provided by IEMEST and funded by the Italian National Operational Programme for Research and Competitiveness 2007–2013 grant (Project code: PONa3_00210, European Regional Development Fund).
Conflict of interest
The authors declare that they have no conflict of interest.
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