Immunohistochemical and Tissue Array Study for Comparison of theExpression of Tumor Suppressor Genes and with IntercellularAdhesive Molecules in Colorectal Adenocarcinoma andNontumoral Colon

Immunohistochemical and Tissue Array Study for Comparison of the Expression of Tumor Suppressor Genes and with Intercellular Adhesive Molecules in Colorectal Adenocarcinoma and Nontumoral Colon

Introduction: Colorectal Carcinoma is a main health problem in manycountries and the third common cancer in Iran. This malignancy atpresent is the most curable carcinoma of gastrointestinal tract. Variationin the expression of the proteins produced by P53, P21, P16, E-cadherin,and β-catenin genes have been noted in this malignancy and may beimportant in the prognosis and therapeutic response rate. The aim of thisstudy was to compare the frequency and pattern of expression of theseproteins in tumoral and nontumoral colonic mucosa. The correlation withprognostic factors including tumor stage, grade, and vascular andperineural invasion was also determined.Material and Methods: The paraffin blocks from tumoral andnontumoral parts of the colon obtained from 58 patients with colorectaladenocarcinoma were studied along with 50 colectomic cases inindividuals without malignancy. Cylindrical tissue fragments wereobtained from appropriate parts of donor blocks by using a 2.5 mmpunch biopsy instrument. Each 30 samples were manually arrayed inone tissue array block. Expression of above genes was investigatedafter sectioning the blocks and immunohistochemical staining of slides.Results: The expression of P53 in tumor cells was significantly morecommon than in colonic nontumor cells and colon of individuals withouttumor (p<0.001); expression of this protein in tumoral tissues wasdirectly related to vascular invasion (p=0.017). The expressionfrequency of P21 and P16 in tumor cells was less than nontumoral tissuesof patients with cancer and patients without cancer (p<0.001). These twogene products showed no correlation with prognostic factors. Theexpression frequency of membranous E-cadherin and β-catenin in tumorcells was not different from controls, while the membranous expressionof E-cadherin was inversely related to cell differentiation (p=0.023) andvascular invasion (p=0.025). In addition, the membranous expression ofβ-catenin was inversely related to vascular invasion (p=0.049).Cytoplasmic and nuclear expression of β-catenin in tumor cells weresignificantly higher than their expression in the controls (p<0.001).Cytoplasmic expression of this marker was inversely related to diseasestage (p=0.013), while its nuclear expression was inversely related tocell differentiation (p=0.012).Conclusion: According to our data, it seems that we are able to predictaggressive capacity of the colorectal tumor by determining the frequencyand pattern of expression of P53, E-cadherin and β-catenin proteins.These studies can be done simply on formalin-fixed small biopsysamples before surgery to provide valuable information for surgeons,gastroenterologists, and oncologists to choose the best therapeuticapproach and predict the therapeutic response. Manual tissue arraymethod is believed to be an economical technique for similar researchprojects.

Introduction: Colorectal Carcinoma is a main health problem in many countries and the third common cancer in Iran. This malignancy at present is the most curable carcinoma of gastrointestinal tract. Variation in the expression of the proteins produced by P53, P21, P16, E-cadherin, and p-catenin genes have been noted in this malignancy and may be important in the prognosis and therapeutic response rate. The aim of this study was to compare the frequency and pattern of expression of these proteins in tumoral and nontumoral colonic mucosa. The correlation with prognostic factors including tumor stage, grade, and vascular and perineural invasion was also determined. Material and Methods: The paraffin blocks from tumoral and nontumoral parts of the colon obtained from 58 patients with colorectal adenocarcinoma were studied along with 50 colectomic cases in individuals without malignancy. Cylindrical tissue fragments were obtained from appropriate parts of donor blocks by using a 2.5 mm punch biopsy instrument. Each 30 samples were manually arrayed in one tissue array block. Expression of above genes was investigated after sectioning the blocks and immunohistochemical staining of slides. Results: The expression of P53 in tumor cells was significantly more common than in colonic nontumor cells and colon of individuals without tumor (p<0.001); expression of this protein in tumoral tissues was directly related to vascular invasion (p=0.017). The expression frequency of P21 and P16 in tumor cells was less than nontumoral tissues of patients with cancer and patients without cancer (p<0.001). These two gene products showed no correlation with prognostic factors. The expression frequency of membranous E-cadherin and B-catenin in tumor cells was not different from controls, while the membranous expression of E-cadherin was inversely related to cell differentiation (p=0.023) and vascular invasion (p=0.025). In addition, the membranous expression of B-catenin was inversely related to vascular invasion (p=0.049). Cytoplasmic and nuclear expression of B-catenin in tumor cells were significantly higher than their expression in the controls (p<0.001). Cytoplasmic expression of this marker was inversely related to disease stage (p=0.013), while its nuclear expression was inversely related to cell differentiation (p=0.012). Conclusion: According to our data, it seems that we are able to predict aggressive capacity of the colorectal tumor by determining the frequency and pattern of expression of P53, E-cadherin and B-catenin proteins. These studies can be done simply on formalin-fixed small biopsy samples before surgery to provide valuable information for surgeons, gastroenterologists, and oncologists to choose the best therapeutic approach and predict the therapeutic response. Manual tissue array method is believed to be an economical technique for similar research projects.