Abstract
BackgroundThe involvement of Heat Shock Proteins (HSP) in cancer development and progression is a widely debated topic. The objective of the present study was to evaluate the presence and expression of HSP60 and HSP10 in a series of large bowel carcinomas and locoregional lymph nodes with and without metastases.Methods82 Astler and Coller's stage C2 colorectal cancers, of which 48 well-differentiated and 34 poorly-differentiated, were selected along with 661 lymph nodes, including 372 with metastases and 289 with reactive hyperplasia only, from the same tumours. Primitive tumours and both metastatic and reactive lymph nodes were studied; specifically, three different compartments of the lymph nodes, secondary follicle, paracortex and medullary sinus, were also analysed. An immunohistochemical research for HSP60 and HSP10 was performed and the semiquantitative results were analysed by statistical analysis to determine the correlation between HSPs expression and 1) tumour grading; 2) degree of inflammation; 3) number of lymph nodes involved; 4) lymph node compartment hyperplasia. Moreover, western blotting was performed on a smaller group of samples to confirm the immunohistochemical results.ResultsOur data show that the expression of HSP60, in both primary tumour and lymph node metastasis, is correlated with the tumoral grade, while the HSP10 expression is not. Nevertheless, the levels of HSP10 are commonly higher than the levels of HSP60. In addition, statistical analyses do not show any correlation between the degree of inflammation and the immunopositivity for both HSP60 and HSP10. Moreover, we find a significant correlation between the presence of lymph node metastases and the positivity for both HSP60 and HSP10. In particular, metastatic lymph nodes show a higher percentage of cells positive for both HSP60 and HSP10 in the secondary follicles, and for HSP10 in the medullary sinuses, when compared with hyperplastic lymph nodes.ConclusionHSP60 and HSP10 may have diagnostic and prognostic significance in the management of this tumour and their overexpression in tumoral cells may be functionally related to tumoral progression. We hypothesise that their expression in follicular and medullary cells of lymph nodes may be induced by formation of metastases. Further studies based on these observations could lead to a better understanding of the HSPs involvement in colorectal cancer progression, as well as other neoplasms.
Highlights
The involvement of Heat Shock Proteins (HSP) in cancer development and progression is a widely debated topic
The percentage of HSP60 positive cells was higher in the G3 group compared with the G1, while a similar number of HSP10 positive elements were present in both groups
Statistical analyses showed that the difference between the number of HSP60 positive cells in G1 and G3 large bowel carcinomas (LBC) was significant (p < 0.0005), while statistic difference was not found in HSP10 positivity (p > 0.05)
Summary
The involvement of Heat Shock Proteins (HSP) in cancer development and progression is a widely debated topic. Heat shock proteins (HSP) are a family of molecules that are highly conserved during evolution and involved in many cellular functions, such as protein folding Their alteration may have multiple pathophysiologic effects and the number of papers studying their expression in normal and pathologic conditions is constantly increasing [1,2,3]. In the last few years, our research group has evaluated the presence and expression of HSP60 and HSP10 in a series of carcinogenetic models, such as the "dysplasia-carcinoma" sequences of uterine exocervix [17,18], large bowel [18,19] and prostate [20] These data have highlighted that these chaperones are overexpressed during the carcinogenetic steps; in particular, they accumulate in the cytoplasm of dysplastic and neoplastic cells, and their levels of expression increases in the sequence leading from dysplasia towards carcinoma. We have hypothesised that HSP60 and HSP10 might be considered as new diagnostic and prognostic tools for these cancers [21,22], being involved in the molecular steps of carcinogenesis, analogously to what has already been demonstrated with other tumours [23,24,25,26,27,28]
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