RESUMO
Background The hypoxia-inducible factor-1 alpha (HIF-1α) is believed to control angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the interLeukin-33 (IL-33) gene and vascular endothelial growth factor (VEGF) gene. The study aimed to study the HIF-1α and its two hypoxia pathway genes; IL-33 and VEGF, together with the angiogenesis and correlate them with some prognostic clinicopathological features, separately and in combination to assess their dependency. Methodology This study included 87 colorectal cancer (CRC) cases, diagnosed between January 2019 and December 2022. Different prognostic clinicopathological features were examined and tissue microarray (TMA) slides were designed to carry out IHC for IL-33 and VEGF scoring in tumor cells, in addition to qualitative interpretation of VEGF expression in tumor vessels. Molecular analysis was performed for HIF-1α and all data were correlated to the clinicopathological features, separately and collectively, to assess the dependency of these factors. Results No statistical correlation could be seen among the IL-33, VEGF, and prognostic clinicopathological features. Whereas analysis of the HIF-1α alone showed significantly high mean expression in patients with distance metastasis and was increased with the increased involvement of the lymph nodes (LNs). However, when the HIF 1-α expression was correlated with the clinicopathological characteristics on the bases of VEGF and IL-33 expressions the significant association with metastasis disappeared in tumor cells and appeared only with the endothelium of the tumor angiogenesis. Moreover, the results conflicted with the LNs involvement. Conclusions These findings may suggest a role of HIF 1-α in the downstream regulation of biomarkers other than the VEGF and IL-33, which needs to uncover pathways and novel factors regulated by the HIF 1-α for the proinflammation and angiogenesis in malignancy.
RESUMO
The harmony between malignant cells and the adjacent microenvironment is a sophisticated subject; however, it seems to play an important role in cancer evolution. This study aimed to assess the microvascular density (MVD) and the mean pericyte number in the tumor and adjacent tissue, and to correlate the results with special histopathological prognostic variables of the tumor. The study included 48 colorectal cancer (CRC) cases diagnosed in the central lab of Duhok. The immunohistochemical (IHC) expressions of the mesenchymal and vascular dissemination markers, erythroblastosis virus E26 oncogene homolog (ERG, a member of the ETS family of transcription factors) and alpha smooth muscle actin (α-SMA) for microvascular density and pericytes, were assessed in tumor cells and in adjacent tissue around the tumor and then correlated to clinicopathological variables with a special concentration on inflammatory reaction, tumor budding, tumor deposition, and lymphovascular invasion. The results showed that the MVD was significantly higher outside the tumor in T1 and T2 compared with T3 and T4. Moreover, it was significantly higher in grade I when compared to grades II and III within the tumor. However, no correlation was found between the MVD and the special histopathological variables that had been studied. On the other hand, the low mean pericyte showed multiple significant associations outside tumor areas, with special histopathological features including a severe inflammatory reaction, a positive tumor deposit, and a negative lymphovascular invasion. These findings may indicate that defective or transformed pericytes around the tumor can participate in the development of the tumor and, subsequently, the outcome and prognosis.
