Biomarker Evaluation In Oral Cancer: Importance Of Tumor Front

Method: Fresh frozen (FF), formalin fixed paraffin embedded (FFPE) samples from healthy volunteers (n=10), patients with oral lichen planus (n=21), and OSCC (n=81) and clinical data were obtained with informed consent after approval from Regional Medical Ethical Committee. Samples were stained with monoclonal antibody for α-SMA (Thermo Scientific) and polyclonal antibody for integrin α11 (Velling, T. et al. JBC 1999) using En-Vision kit (DAKO). The staining for integrin α11 could not be optimized for FFPE material that contained also the tumor front. Data was analyzed using SPSS.

Result: For frozen material, 81% of primary OSCCs were positive for α-SMA and 87% for integrin α11 in fibroblasts of tumor stroma in tumor center. No correlation was found between α-SMA or integrin α11 in frozen sections (tumor center only) and patient survival. For FFPE material, 94.23% of primary OSCCs, all metastases and recurrences were positive for α-SMA fibroblasts. Correlation between presence of α-SMA positive fibroblasts at tumor front, but not in tumor center with patient survival was found. Kaplan-Mayer survival analysis showed that patients with α-SMA positive fibroblasts in network arrangement (α-SMA rich) had significantly poorer prognosis compared to those with spindle shaped α-SMA-positive fibroblasts in tumor stroma (α-SMA poor).

Conclusion: On FF samples correlation was found between α-SMA and integrin α11 staining. On FFPE samples presence of α-SMA positive fibroblasts at tumor front in a network pattern had prognostic value for survival of OSCC patients with carcinomas in other locations than tongue. In addition, we showed the critical importance of assessing tumor front when evaluating the potential of various molecules as prognostic biomarkers in OSCC.