engleski

Apoptotic pathways and stemness in the colorectal epithelium and lamina propria mucosae during the human embryogenesis and carcinogenesis

Aim: Programmed cell death is essential both during normal organ development and carcinogenesis. In this study we immunohistochemically analyzed different pathways of cell death in 11 human conceptuses 5th-10th-weeks old, 10 low and high grade colorectal carcinomas (CRC), and 10 normal colon samples by using markers for apoptosis (caspase-3, AIF, TUNEL), proliferation (Ki-67) and stemness (Oct-4). Results: Between the 5th and 10th week of development, caspase-3 and AIF showed moderate-to-strong expression in the developing gut wall. During development, number of caspase-3-reactive cells decreased, while AIF increased. While healthy colorectal control and low grade CRC showed moderate expression of caspase-3 and AIF, in high grade CRC their expression was strong. Tumor tissues displayed significantly higher number of positive cells than controls. Occasionally, co-expressing of both markers characterized dying cells. In developing colon, Oct-4 and Ki-67 showed moderate-to-strong expression, while some cells co-expressed both markers. Their number decreased in the epithelium and increased in the connective tissue in later development. Healthy colorectal control displayed moderate Ki-67 and mild Oct-4 reactivity. While in low-grade CRC expression Oct-4 and Ki-67 was moderate, in high-grade CRC their expression was strong. Although Oct-4 and TUNEL occasionally co-expressed in all samples, both grades of CRC contained cells that were Oct-4 positive only. Conclusion: Our study revealed two different parallel pathways of cell death, with characteristic increase of AIF-mediated apoptosis when compared to caspase-3, and presence of stemness cells both during colon development and carcinogenesis. These finding might be considered as important diagnostic, survival and CRC therapy predictors.

colorectal carcinoma ; apoptosis ; stemness ; human embryogenesis

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