EXPRESSION OF MMP16 AS A MARKER OF PROGRESSION AND SPREAD OF COLORECTAL CANCER

Background: Remodeling and degradation of the extracellular matrix (ECM) may influence changes in tumor growth and in the capacity of dissemination, possibly augmenting the chance of cancer metastases. The aim of this study is to evaluate the relationship between the expression of genes in the extracellular matrix with histological parameters of neoplastic progression and dissemination in colorectal cancer (CRC). Methods: A retrospective study was conducted regarding patients with CRC stage I - IV who underwent primary tumor resection. Demographics and clinical-pathological data were collected. Tissue specimens were collected from the primary tumor and expression of genes COL6A2, THBS1, VCAM1, MMP1 and MMP16 were determined by real time PCR (RT-PCR) and immunohistochemistry (IHC) assays. Results: 114 cases were eligible; 63 (55.3%) were men, and median age was 60 years of age (range 24-83). As for the location of primary tumor, 41 cases (36.0%) occurred in the right colon, 41 cases (36.0%) in the left colon and 32 cases (28%) in the rectum. Twenty-five (21.9%) patients were staged as TNM stage I, 39 (34.2%) as TNM II, 34 (29.8%) as TNM III and 16 (14.0%) as TNM IV. The most frequent site of metastasis was the liver (9 patients), followed by the peritoneum (three patients), lung (two patients) and ovary (two patients). The expression of MMP16 by immunohistochemistry showed statistical significance using logistic regression when evaluating tumors histological and clinical features in 114 patients: lymphatic invasion (p <0.001), venous invasion (p<0.001), lymph node metastases (p<0.001), distant metastasis (p = 0.002) and advanced stage according to the TNM classification (p<0.001). Analysis made through RT-PCR did not show significant differences. Also, over expression of VCAM-1 and COL6A2 seems to be related to perineural invasion (p = 0.016 and p = 0.022, respectively) and over-expression of THBS-1 to advanced local spread (T3 and T4) (p = 0.002). Conclusion: The expression of the molecule MMP16 by immunohistochemistry technique seems to be related with high risk features and the spread of CRC.

Publication History

Article published online:
23 October 2019