Differential Immunoexpression of BRAF/V600E, Senescence Markers, PTEN, and T-type Calcium Channels in Acquired Naevi According to their Histopathological and Dermoscopic Classification

Authors

  • Sara Moreno Department of Dermatology, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, Avda Alcalde Rovira Roure 80, ES-25198 Lleida, Spain
  • Oscar Maiques
  • Carla Barcelo
  • Marta Romero
  • Maria Santacana
  • Ignacio Gómez
  • Dolors Cuevas
  • Ana Velasco
  • Alvar Vea
  • Anna Macia
  • Ramon Boix
  • Joan Valls
  • Sonia Gatius
  • Carles Canti
  • Xavier Matias-Guiu
  • Xavier Soria
  • Rosa M. Marti

DOI:

https://doi.org/10.2340/actadv.v101.361

Keywords:

acquired melanocytic naevus, BRAF-V600E, senescence markers, PTEN, T-type calcium channels

Abstract

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.

Downloads

Download data is not yet available.

References

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.

https://doi.org/10.2340/00015555-2908 DOI: https://doi.org/10.2340/00015555-2908

Roh MR, Eliades P, Gupta S, Tsao H. Genetics of melanocytic nevi. Pigment Cell Melanoma Res 2015; 28: 661-672.

https://doi.org/10.1111/pcmr.12412 DOI: https://doi.org/10.1111/pcmr.12412

Mesbah Ardakani N. Dysplastic/Clark naevus in the era of molecular pathology. Australas J Dermatol 2019; 60: 186-191.

https://doi.org/10.1111/ajd.13019 DOI: https://doi.org/10.1111/ajd.13019

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.

https://doi.org/10.1016/j.jid.2018.02.012 DOI: https://doi.org/10.1016/j.jid.2018.02.012

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.

https://doi.org/10.1056/NEJMoa1502583 DOI: https://doi.org/10.1056/NEJMoa1502583

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.

https://doi.org/10.1111/bjd.15121 DOI: https://doi.org/10.1111/bjd.15121

Zalaudek I, Catricalà C, Moscarella E, Argenziano G. What dermoscopy tells us about nevogenesis. J Dermatol 2011; 38: 16-24.

https://doi.org/10.1111/j.1346-8138.2010.01141.x DOI: https://doi.org/10.1111/j.1346-8138.2010.01141.x

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.

https://doi.org/10.1111/bjd.15809 DOI: https://doi.org/10.1111/bjd.15809

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.

https://doi.org/10.1111/bjd.13260 DOI: https://doi.org/10.1111/bjd.13260

Braun RP, Rabinovitz HS, Oliviero M, Kopf AW, Saurat JH. Dermoscopy of pigmented skin lesions. J Am Acad Dermatol 2005; 52: 109-121.

https://doi.org/10.1016/j.jaad.2001.11.001 DOI: https://doi.org/10.1016/j.jaad.2001.11.001

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.

https://doi.org/10.1001/archdermatol.2011.149 DOI: https://doi.org/10.1001/archdermatol.2011.149

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.

https://doi.org/10.1111/j.0303-6987.2005.00403.x DOI: https://doi.org/10.1111/j.0303-6987.2005.00403.x

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.

https://doi.org/10.1016/j.ad.2018.10.003 DOI: https://doi.org/10.1016/j.ad.2018.10.003

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.

https://doi.org/10.1016/j.jid.2018.12.033 DOI: https://doi.org/10.1016/j.jid.2018.12.033

Singh RS, Diwan AH, Zhang PS, Prieto VG. Phosphoinositide 3-kinase is not overexpressed in melanocytic lesions. J Cutan Pathol 2007; 34: 220-225.

https://doi.org/10.1111/j.1600-0560.2006.00592.x DOI: https://doi.org/10.1111/j.1600-0560.2006.00592.x

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.

https://doi.org/10.1111/pcmr.12226 DOI: https://doi.org/10.1111/pcmr.12226

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.

https://doi.org/10.1016/j.humpath.2013.10.018 DOI: https://doi.org/10.1016/j.humpath.2013.10.018

Downloads

Published

2021-11-24

How to Cite

Moreno, S., Maiques, O., Barcelo, C., Romero, M., Santacana, M., Gómez, I., Cuevas, D., Velasco, A., Vea, A., Macia, A., Boix, R., Valls, J., Gatius, S., Canti, C., Matias-Guiu, X., Soria, X., & Marti, R. M. (2021). Differential Immunoexpression of BRAF/V600E, Senescence Markers, PTEN, and T-type Calcium Channels in Acquired Naevi According to their Histopathological and Dermoscopic Classification. Acta Dermato-Venereologica, 101(11), adv00597. https://doi.org/10.2340/actadv.v101.361