Prognostic significance of nm23-H1 expression in oral squamous cell carcinoma

Abstract

Recent studies indicated nm23-H1 played a role in cancer progression. Therefore, we investigated clinical significance of nm23-H1 expression in oral squamous cell carcinoma (OSCC). In total, 86 OSCC specimens were immunohistochemically stained with nm23-H1-specific monoclonal antibodies. Immunohistochemical staining of nm23-H1 was confirmed by immunoblotting. The relations between nm23-H1 expression and clinicopathologic variables were evaluated by chi(2) analysis. As increased size of primary tumour could escalate metastatic potential and the data of patients at the late T stage might confound statistical analyses, we thus paid special attention to 54 patients at the early T stage of OSCC. Statistical difference of survival was compared by a log-rank test. Immunohistochemically, nm23-H1 expression was detected in 48.8% (42 out of 86) of tumorous specimens. It positively correlated with larger primary tumour size (P=0.03) and inversely with cigarette-smoking habit (P=0.042). In patients at the early T stage, decreased nm23 expression was associated with increased incidence of lymph node metastasis (P=0.004) and indicated poor survival (P=0.014). Tumour nm23-H1 expression is a prognostic factor for predicting better survival in OSCC patients at the early T stage, which may reflect antimetastatic potential of nm23. Therefore, modulation of nm23-H1 expression in cancer cells can provide a novel possibility of improving therapeutic strategy at this stage. In addition, our results further indicated cigarette smoking could aggravate the extent of nm23-H1 expression and possibly disease progression of OSCC patients.

Figure 1

Immunohistochemical staining for nm23-H1 protein in OSCC. Left: Representative example of positive nm23-H1 expression, which demonstrated intense nm23-H1 immunoreactivity (arrows) in the cytoplasma of tumour cells. Right: Representative example of negative nm23-H1 expression. Arrowhead indicates almost no precipitate in the cytoplasma of tumour cells (original magnification × 400).

Figure 2

Immunoblotting analysis of nm23-H1 expression in the tumourous (T) and nontumourous (N) tissue pairs from 10 patients with OSCC. Extracts from tumour cells or normal oral mucosa derived from the same patients were electrophoresed on a 12% polyacrylamide gel with 4.5% stacking gel. After transfer onto a nitrocellulose membrane, the proteins were immunoblotted with 1 : 500 dilution of mouse monoclonal antibodies specific to nm23-H1, followed by HRP-conjugated goat anti-mouse IgG and development for enhanced chemiluminescence. Molecular weight (in kDa) is shown on the right.

Figure 3

Overall survival curves of patients at the early T-stage OSCC in relation to tumour nm23-H1 expression. The survival analysis was assessed by Kaplan–Meier method and the difference in survival between positive and negative nm23-H1 expression groups was analysed by a log-rank test. The positive nm23-H1 group had significantly better survival than the negative nm23-H1 group (P=0.014).