Association of p53, VEGF and Microvascular Density in Colorectal Carcinoma

Abstract

Introduction: Colorectal Cancer (CRC) is third most common malignancy worldwide. Various genomic alterations play fundamental role in initiation and progression of CRC. Among these, p53 mutation has a crucial role in survival and metastasis and its point mutation induces Vascular Endothelial Growth Factor (VEGF) promoting vascular permeability, migration and differentiation. The degree of angiogenesis can be measured by Microvascular Density (MVD) using CD34, which is helpful in identifying high risk patients for recurrence and metastasis. Aim: The aim of the study was to analyse the expression of p53, VEGF and MVD in CRC and their association with clinicopathological parameters. Materials and Methods: The ambispective study of 2 year duration was conducted from September 2015 to July 2017 in the Department of Pathology, Kalinga Institute of Medical Sciences and PBMH, Bhubaneswar. It included CRC resection specimens and archival tissue blocks. Tissue microarray blocks were prepared manually for IHC application in total 70 cases (58 (82.9%) adenocarcinomas and 12 (17.1%) adenomas) which were histologically staged and graded as per American Joint Committee on Cancer (AJCC) and World Health Organisation (WHO) guidelines. Pearson chi-square test and fisher’s-exact method were used to find significance of p53, VEGF and CD34 expression in adenomas and adenocarcinomas with respect to clinicopathological parameters. Results: No significant statistical association was found between p53, VEGF and MVD with tumour grade and nodal status. Majority, 41 (70.69%) cases were hypervascular (MVD-High). Adenomas 9 (75%) cases, were mostly hypovascular (MVD-Low) with p-value of 0.003. There was significant statistical association between VEGF and MVD with a p-value of 0.01. VEGF and MVD were more expressed on left-sided colon cancers. There was significant statistical association (p=0.01) between p53 graded expression and diagnosis in the present study. MVD and tumour nodal status had an inversely significant relationship (p=0.03). Conclusion: p53 and VEGF expressed more on carcinomas than adenomas. Both p53 and VEGF induce angiogenesis which can be effectively measured by CD34 expression (MVD). There is a directly proportional relationship of angiogenesis and malignant transformation. So these three IHC markers together can be considered a significant prognostic factor involved in CRC.