Keratin 17 expression correlates with tumor progression and poor prognosis in gastric adenocarcinoma.
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.
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. idem@gunma-u.ac.jp
Munenori
M
Ide
Toshihide
T
Kato
Kyoichi
K
Ogata
Erito
E
Mochiki
Hiroyuki
H
Kuwano
Tetsunari
T
Oyama
D048948:14-3-3 Proteins / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary*; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D018450:Disease Progression; D005092:Exonucleases / Q000378:metabolism; D005095:Exoribonucleases; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D053537:Keratin-17 / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism; D055272:Mucin-6 / Q000378:metabolism; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D015260:Neprilysin / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D053537:Keratin-17; D019394:Ki-67 Antigen; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D055271:Mucin 5AC; D055272:Mucin-6; D016159:Tumor Suppressor Protein p53; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D015260:Neprilysin