Neurotrophin receptors and perineural invasion in desmoplastic melanoma

BackgroundPerineural 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.ObjectivesWe investigated the expression of p75NGFR and TrkA, and the presence of functional RET polymorphism (RETp) as they relate to PNI in desmoplastic melanoma.MethodsIn all, 43 cases of desmoplastic melanoma were immunohistochemically evaluated for TrkA and p75NGFR expression and RETp was detected by direct DNA sequencing.ResultsPNI 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).LimitationsThe sample size was limited.ConclusionIn desmoplastic melanoma, p75NGFR expression is significantly associated with PNI and a more locally aggressive phenotype.