Keratin 17 expression correlates with tumor progression and poor prognosis in gastric adenocarcinoma

Ann Surg Oncol. 2012 Oct;19(11):3506-14. doi: 10.1245/s10434-012-2437-9. Epub 2012 Jun 14.

Abstract

Background: Keratin 17 (K17) is regarded as a basal/myoepithelial cell keratin and is known to be inducible in activated keratinocytes. The high frequency of K17 expression in pancreaticobiliary nonmucinous adenocarcinoma or basal-like breast carcinoma has previously been described. However, its expression in gastric cancer (GC) is controversial.

Methods: We investigated the clinicopathological features and prognostic significance of 192 patients with GC by immunohistochemical staining of tissue microarrays. Analysis of epithelial markers including K17, K14, and K5/6, cell cycle-associated proteins p53, Ki-67, and 14-3-3 sigma, and mucinous phenotype markers including CD10, CDX2, MUC5AC, and MUC6 was performed.

Results: Cytoplasmic expression of K17 was observed in 95 (49.5%) of 192 patients with GC. K17 expression positively correlated with lymph node metastasis (P = 0.003) and advanced stages of the disease (P = 0.014). K17 expression was significantly correlated with 14-3-3 sigma expression (P < 0.001) and CD10 expression (P = 0.015). The overall survival rates of patients with K17-positive GC were significantly lower than those with negative K17 expression (50.5 vs. 71.1%, P = 0.004). Univariate analysis revealed that K17 expression confers a poor prognosis in patients with GC (P = 0.004), and it was also an independent prognostic factor in multivariate analysis (P = 0.049).

Conclusions: K17 expression is correlated with tumor progression in GC and may serve as a biomarker for poor prognosis.

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / secondary*
  • Aged
  • Biomarkers, Tumor / metabolism*
  • CDX2 Transcription Factor
  • Disease Progression
  • Exonucleases / metabolism
  • Exoribonucleases
  • Female
  • Homeodomain Proteins / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Keratin-17 / metabolism*
  • Ki-67 Antigen / metabolism
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mucin 5AC / metabolism
  • Mucin-6 / metabolism
  • Multivariate Analysis
  • Neoplasm Staging
  • Neprilysin / metabolism
  • Prognosis
  • Proportional Hazards Models
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • 14-3-3 Proteins
  • Biomarkers, Tumor
  • CDX2 Transcription Factor
  • CDX2 protein, human
  • Homeodomain Proteins
  • Keratin-17
  • Ki-67 Antigen
  • MUC5AC protein, human
  • MUC6 protein, human
  • Mucin 5AC
  • Mucin-6
  • Tumor Suppressor Protein p53
  • Exonucleases
  • Exoribonucleases
  • SFN protein, human
  • Neprilysin