Tumor-stroma ratio, neoangiogenesis and prognosis in laryngeal carcinoma. A pilot study on preoperative biopsies and matched surgical specimens.

OBJECTIVES: The interaction between tumor cells and stroma is critical in tumorigenesis, tumor neo-angiogenesis and cancer progression. The aims of this study were to: (i) evaluate the concordance between tumor-stroma ratio (TSR) and microvascular density (MVD) on paired biopsy and surgical specimens of laryngeal carcinoma (LSCC); (ii) investigate the association of TSR with angiogenesis (CD105- and CD31-assessed MVD); (iii) assess the prognostic role of TSR and MVD evaluated on preoperative biopsies and paired surgical specimens. METHODS: TSR, CD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 43 consecutive cases. RESULTS: TSR showed good agreement between biopsies and surgical specimens (AC1 statistic: 0.7957). In biopsies, TSR low/stroma-rich cases showed higher CD105-assessed MVD (p = 0.0380). In surgical specimens both median CD105- and CD31-assessed MVD were significantly higher in TSR low/stroma-rich than in TSR high/stroma-poor patients (p = 0.0089 and p = 0.0391). In the univariate Cox's model, TSR predicted disease-free survival (DFS) in both biopsies and surgical specimens (p = 0.0003 and p = 0.0002). DFS was associated with CD105- and CD31-assessed MVD in biopsies (p < 0.0001 for both) and surgical specimens (p < 0.0001 for both). Considering biopsies, the multivariate analysis found both TSR (p = 0.0032; HR = 6.112, 95%CI: 1.833-20.378) and CD105-assessed MVD (p = 0.0002; HR = 1.201, 95%CI: 1.090-1.322) as DFS predictor. In paired surgical specimens, both TSR (p = 0.0074; HR = 6.137, 95%CI: 1.626-23.172) and CD105-assessed MVD (p = 0.0005; HR = 1.172 95 %CI 1.071-1.282) retained their significance in multivariate analysis. CONCLUSIONS: If confirmed by large prospective studies, TSR and MVD could be proposed as prognostic biomarkers of LSCC for a possible treatment intensification or targeted therapy.