P53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria.

Tais Fernanda Marcolino,Celina Tizuko Fujiyama Oshima,Paula Castelo,Marcelo Souza Silva,Ricardo Artigiani Neto,Nora Manoukian Forones,Celia Aparecida Marques Pimenta

doi:10.31557/apjcp.2020.21.2.343

Tais Fernanda Marcolino, Celina Tizuko Fujiyama Oshima + Show 5 more

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https://doi.org/10.31557/apjcp.2020.21.2.343

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Abstract

Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. Objective:To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. Patients and Methods:We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. Results:Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. Conclusions:Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.

Highlights

Colorectal cancer (CRC), and gastric cancer (GC) are frequent cause of cancer worldwide
The aim of the study was to evaluate the expression of p53, cyclin D1, β-catenin, APC and c-myc proteins in patients with colorectal cancer or gastric cancer with suspected of Lynch syndrome by Bethesda criteria and loss of expression of MLH1, MSH2, MSH6 and PMS2
We observed in 67% of the patients with CRC or GC with positive criteria of Bethesda absence of MLH1, MSH2, MSH6 and/or PMS2 expression

Summary

Introduction

Colorectal cancer (CRC), and gastric cancer (GC) are frequent cause of cancer worldwide. In Brazil, CRC is the third cause of cancer in men and the second in women and GC is the fourth cause of cancer in men and the fifth in women. Colorectal carcinogenesis of sporadic tumors begins with the APC gene mutation, followed by mutations of the KRAS, DCC and TP53 genes. The APC gene mutation promotes the formation of adenoma and decrease of β-catenin, mediator of the Wnt pathway that controls cell proliferation. Nowadays three pathways of carcinogenesis with different prognosis and therapeutic response are currently described (Collucci, 2013). The most common is the chromosome instability (CIS), the second is the microsatellite instability (MSI), common in hereditary CRC and in 15% of sporadic tumors and the hypermetylation of the CpG islands (CIMP) (Collucci, 2013)

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