Nucleostemin and TWIST as predictive markers for recurrence after neoadjuvant chemotherapy for esophageal carcinoma

Cancer Sci. 2012 Feb;103(2):233-8. doi: 10.1111/j.1349-7006.2011.02142.x. Epub 2011 Dec 8.

Abstract

We recently demonstrated that overexpression of the nucleolar GTP-binding protein nucleostemin drives the fraction of genetically-defined tumor cells that exhibit markers and tumorigenic properties of tumor initiating cells. More specifically, cells that constitutively express elevated levels of nucleostemin exhibit increased TWIST expression; expression of genes that induced pluripotent stem cells; enhanced radioresistance; tumor formation, even when small numbers of cells are implanted; and an increased propensity to metastasize. An immunohistochemical analysis of cancer stem cell markers, such as nucleostemin and TWIST has not been conducted in surgically-resected esophageal squamous cell carcinomas after neoadjuvant chemotherapy. In the present study, we examined the expression of CD133, CD44, nucleostemin, guanine nucleotide-binding protein-like 3-like, and TWIST by immunohistochemistry in a series of 54 surgically-resected specimens of esophageal squamous cell carcinomas after neoadjuvant chemotherapy. We identified that high nucleostemin proportion, TWIST intensity, and advanced pathological N stage were significantly correlated with poor relapse-free survival. Together, these observations imply nucleostemin and TWIST as the predictive markers for postoperative recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antineoplastic Agents* / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / surgery
  • Cell Line, Tumor
  • Cisplatin / therapeutic use
  • Epithelial-Mesenchymal Transition
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / surgery
  • Female
  • Fluorouracil / therapeutic use
  • GTP-Binding Proteins / biosynthesis
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local*
  • Neoplastic Stem Cells
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Peptides / metabolism
  • Prognosis
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • GNL3 protein, human
  • Glycoproteins
  • Hyaluronan Receptors
  • Nuclear Proteins
  • PROM1 protein, human
  • Peptides
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • GTP-Binding Proteins
  • Cisplatin
  • Fluorouracil