The role of matrixmetalloproteinase-2 expression by fibroblasts in perineural invasion by oral cavity squamous cell carcinoma

The mechanisms of perineural invasion (PNI) in oral cavity squamous cell carcinoma are only partially understood, and no studies have specifically investigated the role of perineural fibroblasts in PNI. Here, we identified fibroblasts within the microenvironment of perineural invasion and assessed their expression of matrix metalloproteinase-2 (MMP-2). Tumor specimens from 12 patients with oral cavity squamous cell carcinoma and pathologically-confirmed perineural invasion were stained by immunohistochemistry (IHC) for vimentin (positive control) and MMP-2. Scoring was quantified and compared at nerves involved with PNI and nerves uninvolved with PNI. All 12 patients had perineural fibroblasts around involved and uninvolved nerves as marked by vimentin IHC staining. Perineural fibroblasts had detectable MMP-2 expression at areas of perineural invasion in all 12 patients, but no patients had MMP-2 expression by fibroblasts at nerves without PNI. MMP-2 is expressed by fibroblasts within the microenvironment of perineural invasion, and MMP-2 expression by fibroblasts is a possible mechanism of perineural invasion by oral cavity squamous cell carcinoma. MMP-2 may be an anti-cancer target among oral cavity squamous cell carcinoma patients with PNI.