Correlations among Neural Cell Adhesion Molecule, Nerve Growth Factor, and Its Receptors, TrkA, TrkB, TrkC, and p75NGFR, in Perineural Invasion by Basal Cell and Cutaneous Squamous Cell Carcinomas

Abstract

BACKGROUND Neural cell adhesion molecule; nerve growth factor; and its receptors TrkA, TrkB, TrkC, and p75NGFR regulate unique survival pathways in the cells of different noncutaneous malignancies exhibiting a perineural invasive phenotype. Their expression is currently unknown in basal cell carcinoma and cutaneous squamous cell carcinoma exhibiting perineural invasion. OBJECTIVE The objective was to evaluate neural cell adhesion molecule, nerve growth factor, TrkA, TrkB, TrkC, and p75NGFR expression when perineural invasion occurs in basal cell carcinoma and cutaneous squamous cell carcinoma. METHODS Four basal cell carcinomas and five cutaneous squamous cell carcinomas that were perineural invasion-positive and four basal cell carcinomas and three cutaneous squamous cell carcinomas that were perineural invasion-negative were evaluated for the expression of neural cell adhesion molecule, nerve growth factor, TrkA, TrkB, TrkC, and p75NGFR by immunohistochemical staining. RESULTS For neural cell adhesion molecule, six of eight basal cell carcinomas and two of eight cutaneous squamous cell carcinomas stained positive. For nerve growth factor, seven of nine perineural invasion-positive and six of seven perineural invasion-negative tumors stained moderately or greater. For TrkA, B, and C, the perineural invasion-positive cutaneous squamous cell carcinomas generally stained darker than the perineural invasion-negative cutaneous squamous cell carcinomas. For p75NGFR, four of five perineural invasion-positive cutaneous squamous cell carcinoma stain patterns indicated that p75NGFR expression was higher perineurally than elsewhere in the tumor. CONCLUSION In basal cell carcinoma and cutaneous squamous cell carcinoma, the presence of neural cell adhesion molecule may determine tumor aggression and increased levels of nerve growth factor and TrkA, B, and C may reflect unique survival pathways. Higher levels of expression of Trk receptors in cutaneous squamous cell carcinoma cells may predict perineural invasion and the increased p75NGFR expression found in cutaneous squamous cell carcinoma perineurally may allow p75NGFR immunohistochemical staining to be used for detecting sites of perineural invasion.