Differential Immunoexpression of BRAF/V600E, Senescence Markers, PTEN, and T-type Calcium Channels in Acquired Naevi According to their Histopathological and Dermoscopic Classification
Keywords:acquired melanocytic naevus, BRAF-V600E, senescence markers, PTEN, T-type calcium channels
BRAF/V600E mutation and other cell growth/growth-control mechanisms are involved in naevogenesis and melanomagenesis. Immunoexpression of BRAF/V600E and other molecules (p16, phosphatase and tensin homologue (PTEN), Ki67, hTERT and Cav3.1 and 3.2 calcium channels) were investigated in 80 histopathologically and dermoscopically classified acquired naevi. Regarding BRAF/V600E, dysplastic naevi showed lower immunostaining than common naevi, which was significant in comparison with intradermal naevi, which showed the highest BRAF/V600E histoscore. Junctional naevi showed the lowest BRAF/V600E levels. Globular/cobblestone and reticular dermoscopic patterns were consistently associated with high and low BRAF/V600E immunoexpression, respectively, but Zalaudek’s peripheral globule pattern (CR/PG) showed the highest BRAF/V600E immunoexpression. Among global patterns, the previously not investigated multicomponent pattern showed the lowest BRAF/V600E immunoexpression. Regarding the remaining biomarkers, new immunohistochemical features were found, in particular p16 and PTEN low expression in multicomponent pattern; and Ki67, hTERT and Cav.3.1 high expression in CR/PG. In conclusion, histopathology and dermoscopy provide complementary information regarding the biology of melanocytic naevi.
Martin-Gorgojo A, Requena C, Garcia-Casado Z, Traves V, Kumar R, Nagore E. Dysplastic vs. common naevus-associated vs. de novo melanomas: an observational retrospective study of 1,021 patients. Acta Derm Venereol 2018; 98: 556-562.
Roh MR, Eliades P, Gupta S, Tsao H. Genetics of melanocytic nevi. Pigment Cell Melanoma Res 2015; 28: 661-672.
Mesbah Ardakani N. Dysplastic/Clark naevus in the era of molecular pathology. Australas J Dermatol 2019; 60: 186-191.
Stark MS, Tan JM, Tom L, Jagirdar K, Lambie D, Schaider H, et al. Whole-exome sequencing of acquired nevi identifies mechanisms for development and maintenance of benign neoplasms. J Invest Dermatol 2018; 138: 1636-1644.
Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, et al. The genetic evolution of melanoma from precursor lesions. N Engl J Med 2015; 373: 1926-1936.
Maiques O, Macià A, Moreno S, Barceló C, Santacana M, Vea A, et al. Immunohistochemical analysis of T-type calcium channels in acquired melanocytic naevi and melanoma. Br J Dermatol 2017; 176: 1247-1258.
Zalaudek I, Catricalà C, Moscarella E, Argenziano G. What dermoscopy tells us about nevogenesis. J Dermatol 2011; 38: 16-24.
Tan JM, Tom LN, Jagirdar K, Lambie D, Schaider H, Sturm RA, et al. The BRAF and NRAS mutation prevalence in dermoscopic subtypes of acquired naevi reveals constitutive mitogen-activated protein kinase pathway activation. Br J Dermatol 2018; 178: 191-197.
Marchetti MA, Kiuru MH, Busam KJ, Marghoob AA, Scope A, Dusza SW, et al. Melanocytic naevi with globular and reticular dermoscopic patterns display distinct BRAF V600E expression profiles and histopathological patterns. Br J Dermatol 2014; 171: 1060-1065.
Braun RP, Rabinovitz HS, Oliviero M, Kopf AW, Saurat JH. Dermoscopy of pigmented skin lesions. J Am Acad Dermatol 2005; 52: 109-121.
Zalaudek I, Schmid K, Marghoob AA, Scope A, Manzo M, Moscarella E, et al. Frequency of dermoscopic nevus subtypes by age and body site: a cross-sectional study. Arch Dermatol 2011; 147: 663-670.
Fullen DR, Zhu W, Thomas D, Su LD. hTERT expression in melanocytic lesions: an immunohistochemical study on paraffin-embedded tissue. J Cutan Pathol 2005; 32: 680-684.
de Unamuno Bustos B, Sahuquillo Torralba A, Moles Poveda P, Pérez Simó G, Simarro Farinos J, Llavador Ros M, et al. Telomerase expression in a series of melanocytic neoplasms. Actas Dermosifiliogr 2019; 110: 212-219.
Colebatch AJ, Ferguson P, Newell F, Kazakoff SH, Witkowski T, Dobrovic A, et al. Molecular genomic profiling of melanocytic nevi. J Invest Dermatol 2019; 139: 1762-1768.
Singh RS, Diwan AH, Zhang PS, Prieto VG. Phosphoinositide 3-kinase is not overexpressed in melanocytic lesions. J Cutan Pathol 2007; 34: 220-225.
Masaki T, Wang Y, DiGiovanna JJ, Khan SG, Raffeld M, Beltaifa S, et al. High frequency of PTEN mutations in nevi and melanomas from xeroderma pigmentosum patients. Pigment Cell Melanoma Res 2014; 27: 454-464.
Maiques O, Santacana M, Valls J, Pallares J, Mirantes C, Gatius S, et al. Optimal protocol for PTEN immunostaining; role of analytical and preanalytical variables in PTEN staining in normal and neoplastic endometrial, breast, and prostatic tissues. Hum Pathol 2014; 45: 522-532.
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Copyright (c) 2021 Sara Moreno, Oscar Maiques, Marta Romero, Maria Santacana, Ignacio Gómez, Dolors Cuevas, Ana Velasco, Àlvar Veà, Anna Macià, Carla Barceló, Ramon Boix, Joan Valls, Sonia Gatius, Carles Cantí, Xavier Matias-Guiu, Xavier Soria, Rosa M. Martí
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