Abstract
Hypoxia is prognostically important in colorectal cancer (CRC) therapy. Partial oxygen pressure (pO2) is an important parameter of hypoxia. The correlation between pO2 levels and expression levels of prognostic biomarkers was measured in CRC tissues. Human CRC tissues were collected and pO2 levels were measured by OxyLite. Three methods for tissue fixation were compared, including formalin, Finefix, and Finefix-plus-microwave. Immunohistochemistry (IHC) staining was conducted by using the avidin-biotin complex technique for detecting the antibodies to hypoxia inducible factor-1 (HIF-1) alpha, cytokeratin 20 (CK20), and cell proliferation factor Ki67. The levels of pO2 were negatively associated with the size of CRC tissues. Finefix-plus-microwave fixation has the potential to replace formalin. Additionally, microwave treatment improved Finefix performance in tissue fixation and protein preservation. The percentage of positive cells and gray values of HIF-1 alpha, CK20, and Ki67 were associated with CRC development (P < 0.05). The levels of pO2 were positively related with the gray values of Ki67 and negatively related with the values of HIF-1 alpha and CK20 (P < 0.05). Thus, the levels of microenvironmental pO2 affect the expression of predictive biomarkers HIF-1 alpha, CK20, and Ki67 in the development of CRC tissues.
Highlights
Colorectal cancer (CRC) is the most common malignancy and third-leading cause of cancer death worldwide [1]
The change for hypoxia inducible factor-1 (HIF-1) alpha has been detected in colorectal cancer (CRC) [11, 12] and several authors have described its importance in angiogenesis and CRC growth [13, 14]
27% (45 cases) of CRC were located in the proximal colon, 24% (40 cases) of CRC were located in the distal colon, and 49% (83) of CRC were located in the rectum
Summary
Colorectal cancer (CRC) is the most common malignancy and third-leading cause of cancer death worldwide [1]. HIF-1 (hypoxia inducible factor-1), a kind of hydrocarbon nuclear translators, plays an important role in oxygen homeostasis [7] and consists of two subunits, HIF-1 alpha and HIF-1 beta. HIF-1 alpha is oxygen-mediated factor, which affects HIF bioactivity. HIF-1 alpha can activate genes and their translated proteins, such as erythropoietin [8], glucose transporters [9], and vascular endothelial growth factor (VEGF) [10]. The change for HIF-1 alpha has been detected in colorectal cancer (CRC) [11, 12] and several authors have described its importance in angiogenesis and CRC growth [13, 14]. Ki67, a nuclear protein, affects cellular proliferation and it reflects a reversible change in cellular bioactivity during neoplastic progression [15]. Hypoxia may affect the expression of Oxidative Medicine and Cellular Longevity
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