Neurotrophin receptors and perineural invasion in desmoplastic melanoma

Background: Perineural invasion (PNI) in desmoplastic melanoma is associated with increased local recurrence and reduced disease-free survival. The biological mechanisms underlying PNI remain unclear although several lines of evidence implicate neurotrophins and their receptors. Objectives: We investigated the expression of p75NGFR and TrkA, and the presence of functional RET polymorphism (RETp) as they relate to PNI in desmoplastic melanoma. Methods: In all, 43 cases of desmoplastic melanoma were immunohistochemically evaluated for TrkA and p75NGFR expression and RETp was detected by direct DNA sequencing. Results: PNI was present in 67% of cases. On univariate analysis, p75NGFR was associated with PNI (expression detected in 79% of PNI-positive cases compared with 36% of PNI-negative cases, P=.005), increased Breslow depth (P=.007), and greater Clark level (P=.01). RETp was noted in 28% of cases but was not significantly associated with PNI (P=.27) or other histopathologic variables. TrkA expression was absent in all cases. PNI was associated with increased Breslow depth and Clark level (P=.01 and P=.009, respectively). Controlling for the association between p75NGFR and depth, p75NGFR remained associated with an increased propensity for PNI (odds ratio 4.68, P=.04). Limitations: The sample size was limited. Conclusion: In desmoplastic melanoma, p75NGFR expression is significantly associated with PNI and a more locally aggressive phenotype.