Clinicopathologic and prognostic significance of immunohistochemical expression of HIF-1 alpha, CXCR4 and CA9 in colorectal carcinoma

Abstract

Objective: To investigate the immunohistochemical expressions of HIF-1 alpha, CA9 and CXCR4 in resected human CRC specimens in relation to clinicopathologic and prognostic variables. Methods: A total of 186 patients (mean(SD) age: 56.7(12.6) years, 54.0% were males) with colorectal adenocarcinoma were included in this retrospective study. Resection specimens of the primary tumor were reviewed to confirm the diagnoses and the stage of the disease. Data on age, gender, tumor characteristics (localization, size, macroscopic growth pattern, histologic type, grade, angiolymphatic invasion, TNM stage), applied treatments and clinical outcome (overall survival, local recurrence and distant metastasis) were obtained from the hospital records. Immunohistochemical analysis of tissue specimens was performed to determine HIF-1 alpha, CA9 and CXCR4 expressions. Results: Overall, 94.0% of cases showed HIF-1 alpha immunoreactivity, 89% showed CXCR4 immunoreactivity, and 15.6% showed CA9 immunoreactivity, while weak expression of immunohistochemical markers was noted in 51.1%, 93.0% and 50.5% of cases, respectively. HIF-l alpha expression was higher among males than in females (median (min-max) final score of 6 (0-9) vs. 3 (0-9), p = 0.013). CA9 expressed at higher levels in ulcerovegetative and depressed tumors than in polypoid ones [0(0-9) vs. 0(0-6), p = 0.039]. CXCR4 expression was significantly higher in tumors < 5 cm than >= 5 cm [6(0-9) vs. 3(0-9), p = 0.028] and in grade 1-2 than grade 3 tumors [4(0-9) vs. 3(0-9), p = 0.030]. No significant difference was noted in survival with respect to strength of HIF-1 alpha, CA9 and CXCR4 immunoreactivity. Conclusion: In conclusion, our findings revealed weak-to-moderate HIF-l alpha and CXCR4 immunoreactivity in majority of resection samples, and weak CA9 immunoreactivity in majority of CA9 positive cases. Other than gender (HIF-1 alpha), macroscopic growth pattern (CA9) and tumor size and histologic grade (for CXCR4), none of the clinicopathologic and prognostic factors investigated were associated with expression of immunohistochemical markers and level of immunoreactivity had no impact on survival.