Взаимосвязь структуры микроциркуляторного русла и метастатического потенциала локализованных форм колоректального рака

Abstract

Introduction. Non-metastatic colorectal cancer can recur within five years as distant metastases in about 25% of stage II patients and 50–60% of stage III patients. It is crucial to identify the subgroup of patients with the highest risk of recurrence. Our study aimed to determine the effect of microvascular density (MVD) and pericyte impaired microvessels (PIM) on the risk of metastasis of colorectal adenocarcinomas. Materials and methods. We carried out a retrospective study of the surgical material for colorectal cancer without metastases in regional lymph nodes. The cohorts included cases with synchronous distant metasta-ses (n=53), metachronous metastases (n=45), and without distant metastases (n=53). In the last group, the follow-up period was from 64 up to 92 months. We performed triple immunohistochemical staining: ERG, α-SMA, and Podoplanin. At low magnification, we determined the areas of highest microvessel density, calculated them on an area of 1.0 mm2 with a magnification of x400. The number of microvessels without α-SMA expression was counted, and eventually the microvessel immaturity index Index-V = PIM / MVD was calculated. Results. Normal blood vessels were characterized by the expression of ERG in endothelial cells and α-SMA in pericytes, while at immature tumor microvessels, the latter were absent. The difference in MVD in the groups was statistically insignificant (p=0.414), on average 10/mm2 for non-metastatic tumors and 11/mm2 for metastatic ones. Metastatic tumors showed significantly higher PIM (mean 8/mm2 vs. 2/mm2) and Index-V (mean 0.69 vs. 0.21). Both showed a significant correlation with distant metastases (p <0.001). Conclusion. The data obtained demonstrate that imperfect tumor neovascularization correlates with metasta-sis, which leads to a worse prognosis. The density of microvessels and their structural features are important independent prognostic factors for patients with colorectal cancer. Evaluation of angiogenesis in a tumor in terms of the number and maturity of newly formed vessels enable to elucidate malignant potential of the tumor. Keywords: angiogenesis, pericytes, microvessel density, colorectal cancer, prognosis