Comparable expression of stem markers and damage-responsive proteins in untreated and chemoradiation-treated rectal cancer.

Purpose: Cancer stem cells (CSCs) are suggested to contribute to therapy resistance in rectal cancer. However, histopathological analysis of CSCs is still lacking in rectal cancer.

Methods: The expression of leucine-rich, repeat-containing G protein-coupled receptor 5 (LGR5), proto-oncogene, polycomb ring finger 1 (BMI1), yes-associated transcriptional regulator (YAP) and its paralog TAZ (hereafter, YAP/TAZ), and nuclear β-catenin was compared in untreated and chemoradiation-treated (CRT) rectal cancer by in situ hybridization and immunostaining. Niche factors were also compared in human rectal cancer specimens and the embryonic intestine.

Results: The mean ratios were 15% and 14% for LGR5, 30% and 33% for BMI1, 2.7% and 7.6% for YAP/TAZ, and 38% and 32% for nuclear β-catenin in untreated and CRT rectal cancer, respectively, showing no significant differences for these stem markers following CRT. The stromal expression ratios of YAP/TAZ were 9.7% and 23% in untreated and CRT rectal cancer, which indicated significant upregulation and confirmation of the damage response in the stroma of CRT tumors. In addition, cancer cells co-expressing LGR5 and CDKN1B are also comparable in untreated and CRT rectal cancer. For niche factors, we found that WNT2B and GREM1 were uniformly expressed in rectal cancer with a pattern similar to that of the early embryonic intestine.

Conclusion: The expression of LGR5, BMI1, CDKN1B, and YAP/TAZ was comparable in untreated and CRT rectal cancer. The uniform expression of mesenchymal niche factors might prevent the zonation of the stem cell niche in rectal cancer.