Prognostic significance of biomarkers in squamous cell carcinoma of the tongue: multivariate analysis.
OBJECTIVE
Expression of a panel of biomarkers, such as p53, Bcl-2, Cyclin D1, c-myc, p21ras, c-erb B2, cytokeratin-19 (CK-19), and factor VIII-related antigen (FVIII-RA), was studied together in anterior tongue tumors from the oral cavity and in posterior tongue tumors from the oropharynx of patients with early- and locally advanced-stage disease, to evaluate their prognostic value.


METHODS
The expression of the above-mentioned biomarkers was studied by immunohistochemical localization.


RESULTS
In this study, 18%, 26%, 62%, 75%, 73%, 50%, and 29% of the tumors exhibited p53, Bcl-2, Cyclin D1, c-myc, p21ras, c-erb B2, and CK-19 expression, respectively. Twenty percent of the tumors had a microvessel count of >0.0. The expression of these biomarkers was also correlated with clinicopathologic parameters. In early-stage patients with a tobacco habit, who showed borderline significance for relapse-free survival by Kaplan-Meier survival analysis, this turned out to be significant, with the general linear model univariate survival analysis. In the total group, disease stage emerged as the most significant prognostic factor, followed by c-myc, when Cox forward stepwise regression and general linear model multivariate survival analysis were performed. However, Cyclin D1, which was significant by Cox forward stepwise regression analysis, lost its significance by general linear model multivariate analysis. In patients with early-stage disease, MVC, which was a significant predictor of disease relapse by Cox forward stepwise regression analysis, lost its significance by general linear model analysis because of small number of patients. In patients with locally advanced tongue cancer, multivariate survival analysis of individual biomarkers by both Cox forward stepwise regression and general linear model analysis indicated c-myc expression to be strongly indicative of poor prognosis. However, multivariate analysis of individual markers along with a combination of markers showed that only by Cox forward stepwise regression analysis did the combined expression of markers c-myc, Cyclin D1, and p21ras emerge as a significant independent prognosticator.


CONCLUSIONS
Overall stage emerged as the most significant prognostic indicator of disease outcome. Tobacco habit also affected relapse-free survival in patients with early-stage disease. However, immunostaining of c-myc in the tumors of locally advanced-stage tongue cancer patients might be a potential adjunct to clinical stage in the pathologic evaluation of tongue specimens.
Vora
Hemangini H
HH
Department of Cancer Biology, Division of Molecular Endocrinology, Gujarat Cancer and Research Institute, NCH Compound, Asarwa, Ahmedabad, India.
Shah
Neelam G
NG
Patel
Devendra D
DD
Trivedi
Trupti I
TI
Chikhlikar
Priya R
PR
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D019938:Cyclin D1 / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D016283:Proto-Oncogene Proteins p21(ras) / Q000097:blood; D012044:Regression Analysis; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000097:blood
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)