Cappello Francesco, David Sabrina, Rappa Francesca, Bucchieri Fabio, Marasà Lorenzo, Bartolotta Tommaso E, Farina Felicia, Zummo Giovanni
Sezione di Anatomia Umana, Dipartimento di Medicina Sperimentale, Università degli Studi di Palermo, Italy.
BMC Cancer. 2005 Oct 28;5:139. doi: 10.1186/1471-2407-5-139.
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.
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.
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.
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.
热休克蛋白（HSP）在癌症发生和发展中的作用是一个备受争议的话题。本研究的目的是评估HSP60和HSP10在一系列伴有或不伴有转移的大肠癌及局部区域淋巴结中的存在及表达情况。
选取82例阿斯泰勒和科勒分期为C2期的结直肠癌，其中高分化48例，低分化34例，同时选取来自同一肿瘤的661枚淋巴结，包括372枚有转移的和289枚仅有反应性增生的。对原发肿瘤以及转移和反应性淋巴结进行研究；具体而言，还对淋巴结的三个不同区域，即次级滤泡、副皮质区和髓窦进行了分析。进行了HSP60和HSP10的免疫组织化学研究，并通过统计分析对半定量结果进行分析，以确定HSPs表达与以下因素之间的相关性：1）肿瘤分级；2）炎症程度；3）受累淋巴结数量；4）淋巴结区域增生情况。此外，对一小部分样本进行了蛋白质印迹分析以证实免疫组织化学结果。
我们的数据表明，HSP60在原发肿瘤和淋巴结转移中的表达均与肿瘤分级相关，而HSP10的表达则不然。然而，HSP10的水平通常高于HSP60的水平。此外，统计分析未显示炎症程度与HSP60和HSP10的免疫阳性之间存在任何相关性。而且，我们发现淋巴结转移的存在与HSP60和HSP10的阳性之间存在显著相关性。特别是，与增生性淋巴结相比，转移淋巴结在次级滤泡中HSP60和HSP10双阳性细胞的百分比更高，在髓窦中HSP10阳性细胞的百分比更高。
HSP60和HSP10在该肿瘤的管理中可能具有诊断和预后意义，它们在肿瘤细胞中的过表达可能在功能上与肿瘤进展相关。我们推测它们在淋巴结滤泡和髓细胞中的表达可能是由转移灶的形成诱导的。基于这些观察结果的进一步研究可能会更好地理解HSPs在结直肠癌进展以及其他肿瘤中的作用。
