Low-affinity nerve growth factor receptor (P75 NGFR) as a marker of perineural invasion in malignant melanomas.

Background: Perineural invasion (PNI) is a well-recognized route of tumor extension in cutaneous neoplasms. Despite an established association with increased local recurrences and metastases, the mechanisms responsible for PNI have yet to be elucidated. We hypothesize that P75 NGFR, a nerve growth factor receptor, may be implicated in the pathogenesis of PNI in these tumors.

Methods: P75 NGFR immunohistochemical staining was performed on 47 skin tumors with PNI including invasive squamous cell carcinomas (SCCs = 29), basal cell carcinomas (BCCs = 8) and malignant melanomas (MMs = 10). These were compared with similar lesions without PNI (SCCs = 7, BCCs = 7 and MMs = 9).

Results: P75 NGFR staining was absent in all invasive SCCs irrespective of the presence of PNI (n = 0/36). Two BCCs with PNI (n = 2/8) and three without PNI (n = 3/7) showed focal P75 NGFR staining. Interestingly, 8 of 10 invasive MMs with PNI had positive P75 NGFR expression (80%), in contrast to only 1 of 9 without PNI (11%).

Conclusions: P75 NGFR may play a mechanistic role in invasive MMs demonstrating PNI. Furthermore, its expression may serve as a marker of PNI in those tumors that lack histological evidence of nerve involvement at the time of excision.