BRAF Expression in Keratoacanthoma

Yıl 2019, Cilt: 5 Sayı: 3, 162 - 167, 31.12.2019

Sevda Önder Havva Erdem Mürüvvet Akçay Çelik

https://doi.org/10.19127/mbsjohs.533416

Öz

Objective: Mutations in genes encoding
proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of
tumor entities, including malignant melanoma, thyroid, colon, over carcinomas
and some sarcomas. The increased activity of BRAF V600E leads to downward
signalization activation via mitogen-activated protein kinase (MAPK), which
plays an important role as cell growth, differentiation and survival regulator.
Latest data show BRAF undergoes mutation in nearly 7%
of cancers and this situation makes BRAF another important oncogene in this
pathway. We aimed to
evaluate the relationship between keratacanthoma and BRAF expression.

Methods: 28 cases of keratocanthomas were included in this
study. Sections were taken from the selected blocks with a thickness of 3
microns with poly-lysine coating. BRAF antibody was applied to the tissues. The
obtained preparations were evaluated by light microscopy. It was rated
according to the degree of staining in epidermis.

Results: Areas showing cytoplasmic staining
with BRAF were evaluated in sections. It was observed that there was no
staining in the keratocanthomas, and staining in sebaceous glands and sweat
glands in peripheral basal cells. It was also noted that the sweat glands had
more stain than the sebaceous glands. The cases
included 18 males and 10 females with ages varying from 33 to 85 years. The
duration of the lesions was between one month and one year. Lesion dimensions
varied from 5 to 70 mm, with mean size of 21 mm. There were
14 cases (50%) with head and neck localization, and 14 cases (50%) with
localization other than the head and neck.

Conclusion: As a result, it has been concluded
that BRAF mutation may not be involved in keratoacanthoma.

Anahtar Kelimeler

BRAF, keratoacanthoma, expression

Kaynakça

• Abildgaard C, Guldberg P. Molecular drivers of cellular metabolic reprogramming in melanoma. Trends Mol Med 2015;21:164-71.
• Adackapara CA, Sholl LM, Barletta JA, Hornick JL Immunohistochemistry using the BRAF V600E mutation-specific monoclonal antibody VE1 is not a useful surrogate for genotyping in colorectal adenocarcinoma. Histopathology. 2013 Aug;63(2):187-93.
• Aksoy B, Aksoy HM, Akın O. Keratoacanthoma in an acrochordon. Turkderm-Turk Arch Dermatol Venereolgy 2017;51:24-5.
• Alloo A, Garibyan L, LeBoeuf N, Lin G, Werchniak A, Hodi FS Jr, et al. Photodynamic therapy for multiple eruptive keratoacanthomas associated with vemurafenib treatment for metastatic melanoma. Arch Dermatol.2012 Mar;148(3):363-6.
• Anforth R, Tembe V, Blumetti T, Fernandez-Peñas P. Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors. Pigment Cell Melanoma Res. 2012;25(5):569-72.
• Arnault JP, Mateus C, Escudier B, Tomasic G, Wechsler J, Hollville E, et al. Skin tumors induced by sorafenib; paradoxic RAS-RAF pathway activation and oncogenic mutations of HRAS, TP53, and TGFBR1. Clin Cancer Res. 2012 Jan 1;18(1):263-72.
• Bell D, Aung P, Prieto VG, Ivan D. Next-Generation Sequencing Reveals Rare Genomic Alterations in Aggressive Digital Papillary Adenocarcinoma. Annals of Diagnostic Pathology. 2015; 19(6): 381–384.
• Chauhan A, Chaudhary S, Agnihotri PG, Aadithya B. A solitary crateriform ulcer of the lower lip: a case report with review of literature. Indian J Dermatol. 2011; 56: 435–438.
• Clausen OP, Aass HC, Beigi M, Purdie KJ, Proby CM, Brown VL, et al. Are keratoacanthomas variants of squamous cell carcinomas? A comparison of chromosomal aberrations by comparative genomic hybridization. J Invest Dermatol. 2006; 126: 2308–2315.
• Clynick B, Tabone T, Fuller K, Erber W, Meehan K, Millward M, et al. Mutational Analysis of BRAF Inhibitor-Associated Squamoproliferative Lesions.J Mol Diagn. 2015 Nov;17(6):644-51.
• Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54.
• Estrella JS, Tetzlaff MT, Bassett RL Jr, Patel KP, Williams MD, Curry JL, et al. Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing. Mol Cancer Ther. 2015 Dec;14(12):2887-95.
• Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, et al. RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors. N Engl J Med. 2012; 366(3): 207–215.
• Frouin E, Guillot B, Larrieux M, Tempier A, Boulle N, Foulongne V, et al. Cutaneous epithelial tumors induced by vemurafenib involve the MAPK and Pi3KCA pathways but not HPV nor HPyV viral infection. PLoS One. 2014 Oct 31;9(10):e110478.
• Garnett M, Marais R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 2004;6:313–9.
• Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature. 2010;464 (7287): 431-435.
• Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell. 2010;140(2):209-221.
• Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous cell carcinoma: three examples with metastases. Am J Dermatopathol 1993; 4:332–342.
• Kumar R, Angelini S, Snellman E, Hemminki K. BRAF mutations are common somatic events in melanocytic nevi. J Invest Dermatol 2004;122:342-8.
• Kwiek B, Schwartz RA. Keratoacanthoma (KA): An update and review. J Am Acad Dermatol. 2016 Jun;74(6):1220-33.
• Neville BW, Damm DD, Allen CM, Bouquot JE. Oral & Maxillofacial Pathology. 3th ed , Saunders Co: China; 2009. p. 407.
• Oberholzer PA, Kee D, Dziunycz P, Sucker A, Kamsukom N, Jones R, et al. RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors. J Clin Oncol. 2012;30:316–21.
• Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, et al. High frequency of BRAF mutations in nevi. Nat Genet 2003;33:19-20.
• Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature. 2010;464 (7287): 427-430.
• Putti T, Teh M, Lee Y. Biological behavior of keratoacanthoma and squamous cell carcinoma: telomerase activity and COX-2 as potential markers. Modern Pathology. 2004; 17: 468–475.
• Sarah J. Welsh, Pippa G. Corrie. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol. 2015; 7(2): 122–136.
• Schrama D, Groesser L, Ugurel S, Hafner C, Pastrana DV, Buck CB, et al. Presence of human polyomavirus 6 in mutation-specific BRAF inhibitor-induced epithelial proliferations. JAMA Dermatol. 2014 Nov;150(11):1180-6.
• Tan KB, Tan SH, Aw DC, Jaffar H, Lİm TC, Lee SJ, et al. Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation. J Skin Cancer. 2013;2013:752864. .