Prognostic significance of nm23-H1 expression in esophageal squamous cell carcinoma.
OBJECTIVE
Tumor recurrence and metastasis are major causes of treatment failure in esophageal squamous cell carcinoma (ESCC). Recently, nm23, originally considered to be an anti-metastatic gene, has been reported to associate with various roles in different human cancers. We therefore investigated the clinical significance of nm23-H1 expression in ESCC.


METHODS
Pathological sections were immunohistochemically stained with monoclonal antibody that was specific to nm23-H1. Expression of positive nm23-H1 staining was further confirmed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). The relationship between nm23-H1 expression and clinicopathological variables was examined by statistical analysis. Except for 11 (7%) surgical morality, the remaining 145 patients entered the prognostic analysis. The cisplatin-based chemotherapy was established for the patients with tumor stages at or beyond IIb, or with tumor recurrence. Survival difference between groups was compared by log rank test.


RESULTS
Immunohistochemically, nm23-H1 expression was detected in 39.3% (57/145) of the pathological sections. It was positively correlated with tumor stage (P = 0.002), evident lymphovascular invasion (P < 0.001) and tumor recurrence (P = 0.02). Survival of nm23-H1 positive group was statistically superior to nm23-H1 negative group (P < 0.0001) By multivariate survival analysis, tumor stage, the number of lymph node metastasis and expression of nm23-H1 were the independent prognostic factors for ESCC patients.


CONCLUSIONS
Our study demonstrated that nm23-H1 expression was associated with disease progression in ESCC. However, survival of nm23-H1 positive group was superior to nm23-H1 negative group. This paradoxical result could suppose that nm23-H1 expression might increase cisplatin chemosensitivity and hence improve survival. Screening for nm23-H1 expression in tumor cells may be a potential therapeutic strategy in ESCC patients.
Division of Thoracic Surgery, Department of Surgery, Taipei-Veterans General Hospital and National Yang-Ming University, 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan, ROC. lswang@vghtpe.gov.tw
Liang-Shun
LS
Wang
Kuan-Chih
KC
Chow
Yung-Chang
YC
Lien
Kuang-Tai
KT
Kuo
Wing-Yin
WY
Li
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase