The p75 Neurotrophin Receptor, Relative to Other Schwann Cell and Melanoma Markers, Is Abundantly Expressed in Spindled Melanomas

Abstract

Seventeen cases of spindled melanomas and eleven cases of epithelioid melanomas were immunolabeled with various melanoma and Schwann cell markers. Standard melanoma markers included S100, HMB45, HMB50, tyrosinase, and Melan A. Schwann cell markers included the p75 neurotrophin receptor (p75NTR), glial fibrillary acidic protein (GFAP), and the L1 adhesion protein. The degree of immunocytochemical labeling was scored by levels of both intensity and pervasiveness. The results confirmed a distinct difference in labeling between epithelioid and spindled melanomas. The p75NTR was strongly expressed in spindled melanomas and weakly expressed in the epithelioid melanomas. The usual melanoma markers, including HMB45, HMB50, MelanA, and tyrosinase had the reverse pattern, being strongly expressed in virtually all epithelioid melanomas, but rarely expressed in the spindled variants. S100 was unique among the markers in being expressed by both epithelioid and spindled melanomas. Glial fibrillary acidic protein and L1 adhesion protein were expressed moderately, with preferential labeling of the spindled melanomas. The greatest immunophenotypic difference between spindled and epithelioid melanomas was the high abundance of p75NTR expression in spindled melanomas. The functional significance of the high level of p75 neurotrophin receptor expression may contribute to the high predisposition of perineural extension in the desmoplastic subset of spindled melanomas.

Relationship of uveal and cutaneous malignant melanoma in persons with multiple primary tumors

“…A case-control study 33 of 109 UM patients and 149 controls demonstrated an increased number of clinically atypical nevi in those with UM (for 3 or more atypical nevi vs. none, odds ratio [OR] ϭ 5.1; 95% CI ϭ 1. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. A population-based case-control study 6 of 290 cases found that greater than 10 nevi on the back was a risk factor for UM (vs. none, OR ϭ 1.5; 95% CI ϭ 1.0 -2.3).…”

“…1,4,[7][8][9] Biologically, UMs metastasize hematogenously, involving the liver most frequently, 10 while CMs most often involve the regional lymph nodes. 11 Recent immunolabeling studies 12,13 have shown that common melanoma-associated antigens are expressed differently in the 2 cancers.As another means of evaluating the possibility of shared etiologic factors between UM and CM, we sought to learn whether the two tumors occurred in the same person more frequently than would be expected by chance. The Surveillance, Epidemiology and End Results (SEER) cancer registry collects data on incidence, survival and subsequent primary cancers.…”

“…1,4,[7][8][9] Biologically, UMs metastasize hematogenously, involving the liver most frequently, 10 while CMs most often involve the regional lymph nodes. 11 Recent immunolabeling studies 12,13 have shown that common melanoma-associated antigens are expressed differently in the 2 cancers.…”

Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases

“…Neurofilament expression has, however, been reported in a higher percentage of melanomas in some small series, including those of Eyden et al, 11 Lee et al, 9 and the previously mentioned abstract published by Azam et al 23 Neurofilament expression has also been reported in very rare melanomas showing overt ganglioneuromatous differentiation. 34 With the exception of the abstract published by Azam et al, 23 we are aware of only a single study that has systematically evaluated glial fibrillary acidic protein expression in melanoma, by Iwamoto et al, 35 showing expression in 9/17 (53%) spindled and 2/10 (20%) melanomas. We noted aberrant neurofilament protein and glial fibrillary acidic protein expression in 16% and 9% of tested cases, respectively, confirming these prior observations.…”

Melanoma and the Nervous System – Novel Pathways Mediated by Neurotrophins and Their Receptors

“…Melanomas can be morphologically subdivided in several subtypes, such as epithelioid, pleomorphic spindle cell and desmoplastic melanoma. Iwamoto et al found detectable p75NTR in 13 of 14 benign nevi, primarily in the spindled nevocytic structures within the dermis (Iwamoto et al, 2001). Moreover, p75NTR is weakly expressed in the epithelioid melanomas, while it is highly expressed in desmoplastic and spindle cell melanomas (Iwamoto et al, 1996).…”