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. 2005 Oct 28;5:139.
doi: 10.1186/1471-2407-5-139.

The Expression of HSP60 and HSP10 in Large Bowel Carcinomas With Lymph Node Metastase

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Free PMC article

The Expression of HSP60 and HSP10 in Large Bowel Carcinomas With Lymph Node Metastase

Francesco Cappello et al. BMC Cancer. .
Free PMC article

Abstract

Background: The 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.

Methods: 82 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.

Results: Our 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.

Conclusion: HSP60 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.

Figures

Figure 1
Figure 1
HSP60 positivity in carcinoma (arrow) but not in normal tissues (arrowhead) in specimens from both well differentiated (a) and poorly differentiated (b) tumours (Magnification: 10×). A higher magnification (40×) shows that the positivity is diffuse into cytoplasm of tumoral cells of both G1 (c) and G3 (d) specimens; few positive interstitial (inflammatory) cells were scattered in the interposed stroma. HSP10 is also diffusely expressed by tumoral cells of both G1 (e) and G3 (f) LBC (Magnification: 10×). A higher magnification (40×) of both G1 (g) and G3 (h) shows that the positivity is mainly localised in the cytoplasm of neoplastic elements.
Figure 2
Figure 2
Graphics showing comparison between data obtained by quantitative analyses of HSP60 (a) and HSP10 (b) positive tumoral cells in G1 and G3 Ti and Ni.
Figure 3
Figure 3
Infiltrated lymph nodes from G1 (a) and G3 (b) LBC show tumoral glands positive for HSP60. Metastases also show glands positive for HSP10 in both G1 (c) and G3 (d) carcinomas (Magnification: 40×). HSP60 positivity shows vascular (e) and neural (f) invasion by cancer (Magnification: 10×).
Figure 4
Figure 4
Western blot analyses for the research of HSP60 and HSP10 in tissue extracts of normal colonic mucosa (1), Ti G1 (2), Ti G3 (3), Ni G1 (4) and Ni G3 (5).
Figure 5
Figure 5
Diagrams showing the differences of the mean number of positive cells between HLN and MLN in the lymph node compartments: a) secondary follicles; b) paracortex; c) medullary sinuses.
Figure 6
Figure 6
High magnifications (100×) of immunostaining for HSP60 (a) and HSP10 (b) show cytoplasmic positivity.

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