Immunohistochemical Study And Tissue Array Method For Comparison Between Expression Of Tumor Suppressor Genes And Intercellular Adhesive Molecules In Colorectal Adenocarcinoma And Nontumoral Colon

Document Type : Original Article


1 Pathology Department, Dr. Shariati Hospital, Tehran University

2 Dermatology Department, Firouzabadi Hospital, Iran Medical Science University


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 β-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 β-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 β-catenin was inversely related to vascular invasion (p=0.049). Cytoplasmic and nuclear expression of β-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 β-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.