ABSTRACT
Because of the important role in inflammation and tissue regeneration, toll-like receptors (TLR) are likely candidates to mediate effects of the innate immune system on tumorigenesis. The aim of this study was to investigate the expression and clinical relevance of TLR in colorectal cancer (CRC). The expressions of TLR3, TLR4, TLR7, and TLR9 were analyzed in 104 patients with resectable CRC by immunohistochemistry. The evaluation of the expression consisted on measuring the overall level of TLR expression and by each cell type. The results showed a direct association between the histologic grade of tumor and TLR9 expression by tumor cells. TLR4 expression by tumor cells was significantly associated with a lower rate of tumor recurrence, whereas the expression by fibroblasts was significant and independently associated with a high rate of tumor recurrence and with a shortened overall survival in patients; particularly in tumors from left colon and rectum. Therefore, TLR4 expression by fibroblasts could be a useful prognostic marker in CRC.
Subject(s)
Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Fibroblasts/metabolism , Stromal Cells/metabolism , Toll-Like Receptor 4/metabolism , Adult , Aged , Colorectal Neoplasms/mortality , Colorectal Neoplasms/therapy , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Toll-Like Receptors/metabolismABSTRACT
BACKGROUND: Matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) are of crucial importance in the degradation of the stromal connective tissue and basement membrane components. Study of the behavior of these components might help to predict the aggressiveness of tumors. AIMS: To evaluate the expression and clinical relevance of MMPs and TIMPs for patients with resectable colorectal carcinoma. METHODS: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs-1, 2, 7, 9, 11, 13, and 14, and TIMPs-1, 2 and 3. Determinations were performed in cancer specimens from 104 patients with resectable colorectal cancer. The minimum period of follow-up was 12.5 years for patients without recurrence. To identify specific groups of tumors with distinct expression profiles, the data were analyzed by unsupervised hierarchical cluster analysis. RESULTS: Expression of MMP-11 by fibroblasts and MMP-13 by tumor cells were associated with poor prognosis. The dendrogram revealed first-order division of tumors into two distinct MMP/TIMP molecular profiles, designated group 1 (n = 50) and group 2 (n = 54). Group 2 was characterized by significantly higher expression of MMP-1, 11, and 13, and TIMP-3. CONCLUSION: Our results emphasize the prognostic value of MMP-11 and 13 expression in colorectal cancer.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma/enzymology , Colorectal Neoplasms/enzymology , Matrix Metalloproteinases/metabolism , Tissue Inhibitor of Metalloproteinases/metabolism , Aged , Carcinoma/mortality , Colorectal Neoplasms/mortality , Female , Humans , Male , Middle Aged , Spain/epidemiologyABSTRACT
BACKGROUND/AIMS: The survival of patients with colorectal cancer has not varied appreciably in recent years. The knowledge that genetic factors and disruption in apoptosis could play a role in the etiology and prognosis of patients with sporadic colorectal cancer has opened up new lines of research. We have studied a group of patients with colorectal cancer and the possible influence on the prognosis of immunohistochemical MSH2, M30 cytodeath and cytokeratin 20 expression. METHODOLOGY: Forty-nine consecutive patients with unselected colorectal cancer treated by resection and with a minimum follow-up period of 5 years. Tumor specimens were evaluated by an inmunohistochemical method for MSH2, cytokeratin 18 (M30 cytodeath) and cytokeratin 20 expression and correlated with epidemiological, clinicopathological and survival data. RESULTS: Thirty-four patients were resected with curative intention. At the end of the follow-up period, 25 (51%) had died, the majority (21) in relation to tumor progression, the overall median survival period being 47.9 months (95% CI = 27-86.6). Only vascular invasion, (lower median values), (p = 0.04) was related to MSH2 expression and tumor stage (p = 0.02) with cytokeratin 20. Patients' survival was related to tumoral stage (p = 0.04) and vascular invasion (p = 0.002). MSH2 expression, apoptosis (M30 cytodeath) and cytokeratin 20 staining did not influence the prognosis of patients. CONCLUSIONS: A change in the percentage of tumoral staining cells for MSH2, M30 cytodeath and cytokeratin 20 is frequent in patients with colorectal cancer. Only vascular invasion was correlated with MSH2 expression and stage of disease with cytokeratyn 20. Survival was related to TNM stage and vascular invasion, but not to MSH2, M30 cytodeath or cytokeratin 20 expressions.
