Protein Expression Analysis of Melanocyte Differentiation Antigen TRP-2

Abstract

Melanocyte differentiation antigens such as gp100, tyrosinase, and Melan-A and their corresponding antibodies HMB45, T311, and A103 are major diagnostic tools in surgical pathology. Little is known about tyrosinase-related protein 2 (TRP-2, or dopachrome-tautomerase/DCT) another melanocyte differentiation antigen which is an enzymatic component of melanogenesis. We identified a commercial reagent to TRP-2, monoclonal antibody (mAb) C-9 and undertook a comprehensive analysis to assess its specificity and usefulness for surgical pathology. Subsequently, we analyzed panels of normal tissues and tumors. We show that TRP-2 is regularly expressed in melanocytes of the normal skin. In cutaneous nevi TRP-2 is present in junctional as well as in dermal nevocytes. In malignant tumors, C-9 reactivity is restricted to melanocytic and related lesions and present in 84% and 58% of primary and metastatic melanomas respectively. Ten primary melanomas of the ano-rectal mucosa were all positive. Like the other melanocyte differentiation antigens, TRP-2 was absent in six desmoplastic melanomas. Also, only two of nine angiomyolipomas were TRP-2 positive. We conclude that mAb C-9 is a valuable reagent for the analysis of TRP-2 expression in archival surgical pathology material. The expression pattern of TRP-2 in melanocytic and related lesions appears to parallel other melanocyte differentiation antigens though the overall incidence is lower than other antigens such as Melan-A or gp100.

CD8+ T cell self-tolerance permits responsiveness but limits tissue damage

“…Our studies are intended to provide a better understanding of non-deletional CD8+ T cell tolerance by utilizing a more physiologic and translationally-relevant mouse model in which an epitope from the melanocyte differentiation enzyme tyrosinase-related protein 2 (Trp2) is recognized by CD8+ T cells as either self or foreign. Tyrosinaserelated protein 2, an enzyme involved in melanin biosynthesis encoded by the dopachrome tautomerase (Dct) gene, is normally expressed by melanocytes in the skin in both humans and C57BL/6 mice and is overexpressed by many melanomas (Avogadri et al, 2016;Wang et al, 1996). Using wild-type (WT) mice and a novel Dctdeficient (Dct -/-) strain, we compared responses to Trp2180-188/K b (Trp2/K b ) as a selfversus foreign antigen.…”

Oral melanoacanthoma: Clinicopathological and immunohistochemical features of a case series and a scoping review

“…Accordingly, TRP2‐positive melanocytes were diffusely seen in all cases in the present series. This S100+/HMB45+/Melan‐A+/TRP2+ phenotype suggests that melanocytes of OMA retain the immunoreactivity of normal active melanocytes of the oral mucosa 22,23 . For instance, these markers can show variable sensitivity in mucosal melanoma and an individual marker can render negative staining, reinforcing the need for testing multiple melanocytic markers in cases under suspicion of mucosal melanoma 2,23 …”

“…This S100+/HMB45+/Melan-A +/TRP2+ phenotype suggests that melanocytes of OMA retain the immunoreactivity of normal active melanocytes of the oral mucosa. 22,23 For instance, these markers can show variable sensitivity in mucosal melanoma and an individual marker can render negative staining, reinforcing the need for testing multiple melanocytic markers in cases under suspicion of mucosal melanoma. 2,23 The current study also evidenced that inflammation was a consistent, though not ever-present, microscopic feature of OMA, with a predominance of T-lymphocytes.…”

“…22,23 For instance, these markers can show variable sensitivity in mucosal melanoma and an individual marker can render negative staining, reinforcing the need for testing multiple melanocytic markers in cases under suspicion of mucosal melanoma. 2,23 The current study also evidenced that inflammation was a consistent, though not ever-present, microscopic feature of OMA, with a predominance of T-lymphocytes. The predominance of T-lymphocytes over B-lymphocytes has been reported in other oral lesions such as oral lichen planus, 24 oral eosinophilic ulcer, 25 and chronic graft-versus-host disease.…”

A Case Series With Acquired Dermal Melanocytosis: A Retrospective Study From 2001 to 2018

“…18 TRP-2 is also a necessary cytoplasmic enzyme in melanin biosynthesis regulated by MiTF and a cytoplasmic stain. 19 Hematoxylin and eosin staining was used in all counter stains (Fig. 2).…”