Role of matrix metalloproteinase 2 and 9 in situ mRNA expressions and immunhistochemical staining of PECAM-1 and vWF based intratumoral microvessel density during colorectal tumor progression

Matrix metalloproteinase 2 and 9 are of great value during tumor progression since they preferentially degrade the basement membrane, a key step in tumor invasion, metastases, and to induce vascularisation of tumor tissue. The current study was designed to determine whether MMP-2 and MMP-9 in. situ mRNA expressions would correlate with immunohistochemical analysis of PEC AM-1 or vWF based quantification of intraturnoral microvessel density and whether these possible correlations may have any prognostic application. To achieve our objectives forty archived paraffin embedded colorectal adenocarcinoma samples and their resection margins were enrolled in our study. Twenty patients (50%) were males and twenty (50%) were females with male to female ratio of 1: 1. The mean patients age was 54.75 years (range between 28 and 82 years). Adequate, thin paraffin embedded sections (4u.m thick) of both tumor and resection margins were prepared for each respective biopsy and were used to detect MMP-2 and MMP-9 in situ mRNA expressions based on in situ hybridization technique as well as for quantification of intra-tumoral microvessel density based on Immunohistochemica] analysis for PECAM-1 and vWF as endothelial cell markers. Based on the current outcome, there were significant differences in MMP-2 and MMP-9 in situ mRNA expressions as well as in microvessel density based on PECAM-1 or vWF immunostaining when each tumor sample were compared to its respective resection margin (PO.001, PO.001 and PO.001, PO.001, respectively), when tumor samples were broken down according to their various histopathological variables, non of the four investigated parameters including Finally, the current study focused on the possible correlations among the four investigated parameters in respect to various histopathological variables. In general view, both MMP-2 and MMP-9 in situ mRNA expressions as well as PECAM-1 and vWF immunostaining demonstrated significant positive correlations in tumor samples (r=0.88 and r=0.37, respectively) whereas in resection margins, these correlations were absent. Interestingly, MMP-2 and MMP-9 in situ mRNA expressions were found to correlate positively as well as significantly within tumor differentiation (WD: r=0.78, MD: r=0.90, and PD: r-0.91), tumor stage (A-B: r=0.70 and C-D: r=0.95), depth of invasion (SMP: r=0.77, SE: r=0.87, and OR: r=0.97), Lymph node metastasis (NO: r=0.82, Nl: r-0.92, and N2: r=0.96), and tumor size (<3mm3: r=0.76 versus >3mm3:r=0.94). On the other hand, although PECAM-1 and vWF immunostaining revealed significant and positive correlations within tumor differentiation (WD: r=0.56, MD: r=0.57, and PD: r=0.89) as well as with tumor stage (A-B: r=0.39 and C-D: r--0.31), still, unlike MMP-2 and MMP-9 case, they seem to correlate significantly and exclusively within SE group (r=0.74), tumors <3mm3 in size (r=0.66); NO (r=0.36), and Nl (r=0.85) groups. However, PECAM-1 and vWF immunostaining revealed significant but negative correlation exclusively within N2 group (r= -0.38). Moreover, the current study has demonstrated a number of mixed correlations among the four investigated parameters. Interestingly, for MMP-9 in situ mRNA expression, it demonstrated positive significant correlations with PECAM-1 immunostaining within OR and within N2 groups (r-0.52, and r=0.53, respectively). Whereas, for MMP-2 in situ mRNA expression it demonstrated positive significant correlations exclusively with t'HCAM-1 immunostaining within A-B stage group (r=0.33), OR group (rO.67), SM P group (i=0.3 9), and within N2 group (r=0.61). In conclusion, overexpression of MMP-2 and MMP-9 are seemed to be associated v/ith increased angiogenic potential of colorectal adinocarcinoma. Therefore, elevated MMP-2 and MMP-9 expressions might possibly associate with tumor progression, and could be used as targets for therapeutic management of patients with primary colorectal adinocarcinoma. In addition, MMP-2 and MMP-9 in situ mRNA expressions seem to modulate intratumoral microvessel count. Finally, microvessel count could be useful as a predictor for tumor metastases in patients with colorectal adinocarcinoma. Possible interpretations of the current outcome are explained thoroughly in the text.