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.


OBJECTIVE
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).


CONCLUSIONS
The sample size was limited.


CONCLUSIONS
In desmoplastic melanoma, p75NGFR expression is significantly associated with PNI and a more locally aggressive phenotype.
Division of Graduate Medical Sciences, Boston University School of Medicine, Boston, Massachusetts.
Noah
N
Frydenlund
School of Public Health, Boston University School of Medicine, Boston, Massachusetts.
Dominick A
DA
Leone
University of Florida College of Medicine, Gainesville, Florida.
Brendon
B
Mitchell
Department of Pathology, Boston University School of Medicine, Boston, Massachusetts.
Shi
S
Yang
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts.
April
A
Deng
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Mai P
MP
Hoang
Dermatopathology, Section, Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts. Electronic address: mmahalin@bu.edu.
Meera
M
Mahalingam
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009419:Nerve Tissue Proteins / Q000032:analysis; D010525:Peripheral Nerves / Q000473:pathology*; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000032:analysis*; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000473:pathology*; D000096142:Cutaneous Malignant Melanoma
C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
RET; TrkA; desmoplastic melanoma; immunohistochemistry; neurotrophin; p75NGFR; perineural invasion