- Volume 30 Issue 5
DOI QR Code
Sensitivity and Usefulness of VE1 Immunohistochemical Staining in Acral Melanomas with BRAF Mutation
- Suh, Min Song (Department of Dermatology, Chonnam National University Medical School) ;
- Choi, Yoo Duk (Department of Pathology, Chonnam National University Medical School) ;
- Lee, Jee-Bum (Department of Dermatology, Chonnam National University Medical School) ;
- Lee, Seung-Chul (Department of Dermatology, Chonnam National University Medical School) ;
- Won, Young Ho (Department of Dermatology, Chonnam National University Medical School) ;
- Yun, Sook Jung (Department of Dermatology, Chonnam National University Medical School)
- Received : 2017.10.13
- Accepted : 2018.06.07
- Published : 2018.10.01
Background: Acral melanomas are known to have a low frequency of BRAF mutation, in contrary to higher KIT mutation. Recently, VE1 immunostaining was reported to have a good correlation with BRAF mutation status. Objective: We aimed to evaluate the clinicopathological features of BRAF-mutated acral melanomas and validate the correlation of the VE1 immunohistochemical stains in those cases. Methods: The clinical features (age, sex, anatomical site), and histopathological characteristics of 41 patients with acral melanoma were evaluated. We performed a next-generation sequencing to detect BRAF mutation status. We also determined the correlation of VE1 immunohistochemical staining with BRAF mutation status. Results: Among 19 acral melanomas with BRAF mutation, common histopathological subtype was acral lentiginous melanoma (8/19, 42%) and nodular melanoma (8/19, 42%) and superficial spreading melanoma (3/19, 16%) followed. VE1 immunostaining results were positive in all 15 cases with BRAF V600E mutation (sensitivity 100%), and negative in 4 cases of BRAF non-V600E mutation. However, VE1 immunostaining was negative in all 22 patients with BRAF wild-type. Conclusion: VE1 immunostaining had a good correlation with BRAF V600E mutation status.
Supported by : National Research Foundation of Korea (NRF)
- Kim SY, Yun SJ. Cutaneous melanoma in Asians. Chonnam Med J 2016;52:185-193. https://doi.org/10.4068/cmj.2016.52.3.185
- National Cancer Institute. FDA approval for vemurafenib [Internet]. Rockville, MD: National Cancer Institute [cited 2011 Sep 9]. Available from: http://cancer.gov/about-cancer/treatment/drugs/fda-vemurafenib.
- Wilson MA, Nathanson KL. Molecular testing in melanoma. Cancer J 2012;18:117-123. https://doi.org/10.1097/PPO.0b013e31824f11bf
- National Cancer Institute. FDA approval for Dabrafenib [Internet]. Rockville, MD: National Cancer Institute [cited 2013 Jun 21]. Available from: https://www.cancer.gov/aboutcancer/treatment/drugs/dabrafenib.
- Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-954. https://doi.org/10.1038/nature00766
- Rubinstein JC, Sznol M, Pavlick AC, Arian S, Cheng E, Bacchiocchi A, et al. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. J Transl Med 2010;8:67. https://doi.org/10.1186/1479-5876-8-67
- Edlundh-Rose E, Egyhazi S, Omholt K, Mansson-Brahme E, Platz A, Hansson J, et al. NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res 2006;16:471-478. https://doi.org/10.1097/01.cmr.0000232300.22032.86
- Saldanha G, Potter L, Daforno P, Pringle JH. Cutaneous melanoma subtypes show different BRAF and NRAS mutation frequencies. Clin Cancer Res 2006;12:4499-4505. https://doi.org/10.1158/1078-0432.CCR-05-2447
- Lang J, MacKie RM. Prevalence of exon 15 BRAF mutations in primary melanoma of the superficial spreading, nodular, acral, and lentigo maligna subtypes. J Invest Dermatol 2005;125:575-579. https://doi.org/10.1111/j.0022-202X.2005.23833.x
- Jin SA, Chun SM, Choi YD, Kweon SS, Jung ST, Shim HJ, et al. BRAF mutations and KIT aberrations and their clinicopathological correlation in 202 Korean melanomas. J Invest Dermatol 2013;133:579-582. https://doi.org/10.1038/jid.2012.338
- Hong JW, Lee S, Kim DC, Kim KH, Song KH. Prognostic and clinicopathologic associations of BRAF mutation in primary acral lentiginous melanoma in Korean patients: a preliminary study. Ann Dermatol 2014;26:195-202. https://doi.org/10.5021/ad.2014.26.2.195
- Pearlstein MV, Zedek DC, Ollila DW, Treece A, Gulley ML, Groben PA, et al. Validation of the VE1 immunostain for the BRAF V600E mutation in melanoma. J Cutan Pathol 2014;41:724-732. https://doi.org/10.1111/cup.12364
- Marin C, Beauchet A, Capper D, Zimmermann U, Julie C, Ilie M, et al. Detection of BRAF p.V600E mutations in melanoma by immunohistochemistry has a good interobserver reproducibility. Arch Pathol Lab Med 2014;138:71-75. https://doi.org/10.5858/arpa.2013-0031-OA
- Capper D, Preusser M, Habel A, Sahm F, Ackermann U, Schindler G, et al. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol 2011;122:11-19. https://doi.org/10.1007/s00401-011-0841-z
- Long GV, Wilmott JS, Capper D, Preusser M, Zhang YE, Thompson JF, et al. Immunohistochemistry is highly sensitive and specific for the detection of V600E BRAF mutation in melanoma. Am J Surg Pathol 2013;37:61-65. https://doi.org/10.1097/PAS.0b013e31826485c0
- Manfredi L, Meyer N, Tournier E, Grand D, Uro-Coste E, Rochaix P, et al. Highly concordant results between immunohistochemistry and molecular testing of mutated V600E BRAF in primary and metastatic melanoma. Acta Derm Venereol 2016;96:630-634. https://doi.org/10.2340/00015555-2326
- Capper D, Berghoff AS, Magerle M, Ilhan A, Wohrer A, Hackl M, et al. Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. Acta Neuropathol 2012;123:223-233. https://doi.org/10.1007/s00401-011-0887-y
- Yaman B, Kandiloglu G, Akalin T. BRAF-V600 Mutation heterogeneity in primary and metastatic melanoma: a study with pyrosequencing and immunohistochemistry. Am J Dermatopathol 2016;38:113-120. https://doi.org/10.1097/DAD.0000000000000404
- Li H, Drubin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009;25:1754-1760. https://doi.org/10.1093/bioinformatics/btp324
- DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 2010;43:491-498.
- Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G, Levy-Moonshine A, et al. From FastQ data to high confidence variant calls: the genome analysis toolkit best practices pipeline. Curr Protoc Bioinformatics 2013;43:11.10.1-33.
- Wilm A, Aw PP, Bertrand D, Yeo GH, Ong SH, Wong CH, et al. LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets. Nucleic Acids Res 2012;40:11189-11201. https://doi.org/10.1093/nar/gks918
- Wei Z, Wang W, Hu P, Lyon GJ, Hakonarson H. SNVer: a statistical tool for variant calling in analysis of pooled or individual next-generation sequencing data. Nucleic Acids Res 2011;39:e132. https://doi.org/10.1093/nar/gkr599
- Hayward NK, Wilmott JS, Waddell N, Johansson PA, Field MA, Nones K, et al. Whole-genome landscapes of major melanoma subtypes. Nature 2017;11:545:175-180.
- Wu X, Yan J, Dai J, Ma M, Tang H, Yu J, et al. Mutations in BRAF codons 594 and 596 predict good prognosis in melanoma. Oncol Lett 2017;14:3601-3605. https://doi.org/10.3892/ol.2017.6608
- Boursault L, Haddad V, Vergier B, Cappellen D, Verdon S, Bellocq JP, et al. Tumor homogeneity between primary and metastatic sites for BRAF status in metastatic melanoma determined by immunohistochemical and molecular testing. PLoS One 2013;8:e70826. https://doi.org/10.1371/journal.pone.0070826
- Rapisuwon S, Busam KJ, Parks K, Chapman PB, Lee E, Atkins MB. Discordance between cobas BRAF V600 testing and VE1 immunohistochemistry in a melanoma patient with bone marrow metastases. Am J Dermatopathol 2016;38:687-689. https://doi.org/10.1097/DAD.0000000000000660
- Heinzerling L, Kuhnapfel S, Meckbach D, Baiter M, Kaempgen E, Keikavoussi P, et al. Rare BRAF mutations in melanoma patients: implications for molecular testing in clinical practice. Br J Cancer 2013;108:2164-2171. https://doi.org/10.1038/bjc.2013.143
- Ihle MA, Fassunke J, Konig K, Grunewald I, Schlaak M, Kreuzberg N, et al. Comparison of high resolution melting analysis, pyrosequencing, next generation sequencing and immunohistochemistry to conventional Sanger sequencing for the detection of p.V600E and non-p.V600E BRAF mutations. BMC Cancer 2014;14:13. https://doi.org/10.1186/1471-2407-14-13