Abstract
Simple SummaryThis retrospective study (Slovakian population study) brings information about immunohistochemical detection of CAIX and survivin in 74 samples of human colorectal adenocarcinoma and comparison their expression with expression in healthy colon tissue. Our results show that all of samples with healthy colon tissue were CAIX and survivin-negative and there is no statistically significant dependence of these proteins and the chosen clinicopathological parameters. These findings demonstrate that detection of these proteins could be useful for tumor diagnostic and prognostic and CAIX and survivin could represent independent negative prognostic markers of colorectal cancer.The aim of this study was to detect carbonic anhydrase IX (CAIX) and survivin in the colorectal adenocarcinoma cells of the Slovakian population. We used an indirect three-step immunohistochemical method with DAB staining for the localization of the proteins and investigation their expression. We compared their expression with expression in healthy colorectal tissue. In 74 tissues of colorectal adenocarcinomas, 42% showed CAIX positivity and 20% showed survivin positivity. Brown membrane immunostaining was visible in CAIX-positive tumors. Survivin-positive tumors had strong brown cytoplasmic immunostaining. Co-expression of both proteins was present in five specimens (7%). The samples of normal colorectal tissue (without carcinoma) were CAIX-negative and survivin-negative. We also applied the Chi-squared test for evaluation statistically significant association between the expression of proteins and selected clinical and histopathological parameters. We did not find any statistically significant correlations between CAIX or survivin expression and sex of patients, the grade of the tumor, nodal status and presence of metastasis (p > 0.05). The fact that all samples of normal colorectal tissue were CAIX- and survivin-negative could lead to the possibility of using these two proteins as potential tumor diagnostic markers. On the basic of the available publications and data, we suggest that CAIX and survivin could be negative independent prognostic markers of colorectal cancer, which could affect response to therapy.
Highlights
Colorectal cancer represents a global health problem, being, for example, the second most common cause of cancer death in the United States [1]
Tumor cells have to adapt to these conditions if they want to survive and Carbonic anhydrase IX (CAIX) plays a major role in this adaptation process [6]
The interaction of the PG domain of CAIX and catenin causes a decreased E-cadherin-mediated cell adhesion, and the deregulated cell–cell adhesion is a prerequisite for tumor invasion and formation of metastasis [7]
Summary
Colorectal cancer represents a global health problem, being, for example, the second most common cause of cancer death in the United States [1]. Tumor cells have to adapt to these conditions if they want to survive and CAIX plays a major role in this adaptation process [6]. The interaction of the PG domain of CAIX and catenin causes a decreased E-cadherin (epithelial cadherin)-mediated cell adhesion, and the deregulated cell–cell adhesion is a prerequisite for tumor invasion and formation of metastasis [7]. CAIX exosomes induce expression of MMP-2 (matrix metalloproteinase 2), and MMP-2 cleaves major macromolecules of the extracellular matrix as collagen IV, which plays critical roles in cell migration, invasion of cells and metastasis formation [8,9]. Another study showed an increased resistance of tumor cells to therapy associated with high expression of CAIX [10]
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