Nuclear Expression of CD133 Is Associated with Good Prognosis in Patients with Colorectal Adenocarcinoma

Anticancer Res. 2018 Aug;38(8):4819-4826. doi: 10.21873/anticanres.12792.

Abstract

Background/aim: Prominin-1 (CD133) has been suggested as a potential marker of cancer stem cells (CSCs) in various cancer types. The aim of this study was to compare CD133 expression between adenoma cells, colorectal adenocarcinoma (CRAC) cells, and tumor microenvironment cells (TMEs) in terms of the adenoma-carcinoma sequence and to investigate the clinicopathological value of CD133 expression in CRACs as a prognostic marker.

Materials and methods: A total of 58 adenomas and 132 primary and 27 metastatic CRACs were examined for CD133 expression by immunohistochemistry. The cytoplasmic and nuclear expression levels of CD133 were scored by semi-quantitative methods.

Results: Adenomas showed significantly lower cytoplasmic and nuclear CD133 expression than CRACs (p<0.001). Among the CRACs, primary CRACs demonstrated higher cytoplasmic and nuclear expression levels of CD133 than metastatic CRACs (p<0.001). Furthermore, decreased nuclear CD133 expression in CRACs was correlated with a poor outcome, including disease-free survival (DFS), by univariate and multivariate analyses (p=0.012 and p=0.039). For TMEs, adenomas showed a significantly higher CD133 expression than CRACs (p<0.001), and decreased expression of CD133 in CRACs was correlated with shorter DFS by univariate and multivariate analyses (p=0.004 and p=0.042).

Conclusion: Cytoplasmic and nuclear CD133 expression in CRAC cells and TMEs may play an important role in early CRAC carcinogenesis, while decreased CD133 nuclear expression in CRAC cells may contribute to CRAC metastasis. Further prognostic and therapeutic stratification may be performed according to CD133 localization.

Keywords: CD133; adenoma; colorectal adenocarcinoma; stem cell; tumor microenvironment.

Publication types

  • Comparative Study

MeSH terms

  • AC133 Antigen / biosynthesis*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenoma / pathology
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Carcinogenesis / pathology
  • Cell Nucleus / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Cytoplasm / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Tumor Microenvironment

Substances

  • AC133 Antigen
  • Biomarkers, Tumor
  • PROM1 protein, human