Neurotrophin receptors and perineural invasion in desmoplastic melanoma

Abstract

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.

Keywords: RET; TrkA; desmoplastic melanoma; immunohistochemistry; neurotrophin; p75NGFR; perineural invasion.