Νεοαγγείωση καρκίνου παχέος εντέρου: μορφομετρική μελέτη

Abstract

Background: Neovascularization reportedly is correlated with metastasis, recurrence, and prognosis in many types of solid tumors. Microvessel quantification in so-called "hot spots" has been studied extensively as the only factor reflecting angiogenesis in various malignant tumors. The objective of this study was to evaluate multiple morphometric microvascular characteristics in addition to microvessel density (MVD) in colorectal carcinomas to provide a better approach to examining the relation between angiogenesis and clinicopathologic factors and prognosis. Methods: Histologic sections from 106 colorectal adenocarcinomas and 17 adenomas, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to the vessel size (area, major axis length, minor axis length, perimeter, Feret diameter), shape (compactness, shape factor) or immunostaining intensity (proportion of intensely stained areas in relation to the total immunostained surface). Of the 123 cases investigated, 103 finally were evaluable in the statistical analysis, responding to the criteria of a high quality image depiction. Results: Carcinomas presented higher counts of microvessels compared to adenomas. MVD appeared to decrease with increasing Dukes stage. Carcinomas of lower Dukes stages (A and B) had a higher mean MVD than those of advanced stages (C and D). Although the difference did not reach statistical significance, well-differentiated neoplasms had lower MVD values than poorly differentiated ones. MVD was significantly correlated with the shape factor and compactness. All the morphometric parameters related to the size of microvessels had lower values in the group of adenomas. These parameters where significantly increased with progressing Dukes stage. Carcinomas with a higher histological differentiation had a significantly reduced TVA as compared to tumors with moderate or poor differentiation. Well-differentiated tumors had significantly lower values of shape factor and higher values of compactness in relation to poorly differentiated neoplasms. The vascular branching counts were significantly higher in carcinomas than in adenomas, and remained unaffected through progressing Dukes stages. Adenomas presented a more intense immunoreaction to FVIII as compared to carcinomas. Branching counts and TVA were the only factors of prognostic significance. Conclusions: This study provides evidence that neovascularization is an early critical event in colorectal tumorigenesis, reaching a maximum level early in the malignant process. Its prognostic significance is better assessed by quantification of TVA and the branching pattern of microvessels, whereas MVD does not provide significant prognostic information for colorectal carcinoma patients.