Predictive biomarkers and tumor microenvironment in female genital melanomas: a multi-institutional study of 55 cases.
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
28
04
2019
accepted:
11
07
2019
revised:
11
07
2019
pubmed:
7
8
2019
medline:
15
12
2020
entrez:
7
8
2019
Statut:
ppublish
Résumé
Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital melanomas is limited. We evaluated the clinicopathological features of 20 vulvar, 32 vaginal, and three cervical melanomas and assessed programmed cell death ligand 1 (PD-L1) expression, CD8 tumor-infiltrating lymphocyte density, mismatch repair proteins, VE1 immunohistochemistry, and KIT and BRAF mutations. The median age of the patients was 66 years, and median tumor sizes were 25, 30, and 20 mm for vulvar, vaginal, and cervical tumors, respectively. Mean mitotic figures were 18, 19, and 30 per mm
Identifiants
pubmed: 31383965
doi: 10.1038/s41379-019-0345-2
pii: S0893-3952(22)00953-X
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
138-152Références
Ragnarsson-Olding B, Nilsson B, Kanter-Lewensohn L, Lagerlöf B, Ringborg U. Malignant melanoma of the vulva in a nationwide, 25-year study of 219 Swedish females: predictors of survival. Cancer. 1999;86:1285.
pubmed: 10506715
doi: 10.1002/(SICI)1097-0142(19991001)86:7<1285::AID-CNCR25>3.0.CO;2-P
Sugiyama VE, Chan JK, Shin JY, Berek JS, Osann K, Kapp DS. Vulvar melanoma: a multivariable analysis of 644 patients. Obstet Gynecol. 2007;110:296–301.
pubmed: 17666603
doi: 10.1097/01.AOG.0000271209.67461.91
Weinstock MA. Malignant melanoma of the vulva and vagina in the United States: patterns of incidence and population-based estimates of survival. Am J obstet Gynecol. 1994;171:1225–30.
pubmed: 7977524
doi: 10.1016/0002-9378(94)90137-6
Leitao MM Jr, Cheng X, Hamilton AL, Siddiqui NA, Jurgenliemk-Schulz I, Mahner S, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for vulvovaginal melanomas. Int J Gynecol Cancer. 2014;24:S117–S22.
pubmed: 24987924
doi: 10.1097/IGC.0000000000000198
Yin C, Yang A, Zhang Y, Tao L, Zou H, Ren Y, et al. Primary cervical malignant melanoma: 2 cases and a literature review. Int J Gynecol Pathol. 2019;38:196–203.
pubmed: 29474317
doi: 10.1097/PGP.0000000000000480
Gadducci A, Carinelli S, Guerrieri ME, Aletti GD. Melanoma of the lower genital tract: Prognostic factors and treatment modalities. Gynecol Oncol. 2018;150:180–9.
pubmed: 29728261
doi: 10.1016/j.ygyno.2018.04.562
Gupta D, Malpica A, Deavers MT, Silva EG. Vaginal melanoma: a clinicopathologic and immunohistochemical study of 26 cases. Am J Surg Pathol. 2002;26:1450–7.
pubmed: 12409721
doi: 10.1097/00000478-200211000-00007
Khoo U, Collins R, Ngan H. Malignant melanoma of the female genital tract: a report of nine cases in the Chinese of Hong Kong. Pathology. 1991;23:312–7.
pubmed: 1784522
doi: 10.3109/00313029109063595
Mert I, Semaan A, Winer I, Morris RT, Ali-Fehmi R. Vulvar/vaginal melanoma: an updated surveillance epidemiology and end results database review, comparison with cutaneous melanoma and significance of racial disparities. Int J Gynecol Cancer. 2013;23:1118–25.
pubmed: 23765206
doi: 10.1097/IGC.0b013e3182980ffb
Tcheung WJ, Selim MA, Herndon JE, Abernethy AP, Nelson KC. Clinicopathologic study of 85 cases of melanoma of the female genitalia. J Am Acad Dermatol. 2012;67:598–605.
pubmed: 22243767
doi: 10.1016/j.jaad.2011.11.921
Bradish JR, Montironi R, Lopez-Beltran A, Post KM, MacLennan GT, Cheng L. Towards personalized therapy for patients with malignant melanoma: molecular insights into the biology of BRAF mutations. Future Oncol. 2013;9:245–53.
pubmed: 23414474
doi: 10.2217/fon.12.179
Schadendorf D, Fisher DE, Garbe C, Gershenwald JE, Grob JJ, Halpern A, et al. Melanoma. Nat Rev Dis Prim. 2015;1:15003.
pubmed: 27188223
doi: 10.1038/nrdp.2015.3
Cooper ZA, Juneja VR, Sage PT, Frederick DT, Piris A, Mitra D, et al. Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol Res. 2014;2:643–54.
pubmed: 24903021
pmcid: 4097121
doi: 10.1158/2326-6066.CIR-13-0215
Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4:127ra37.
pubmed: 22461641
pmcid: 3568523
doi: 10.1126/scitranslmed.3003689
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–71.
pubmed: 25428505
pmcid: 4246418
doi: 10.1038/nature13954
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32:1020–30.
pubmed: 24590637
pmcid: 4811023
doi: 10.1200/JCO.2013.53.0105
Hou JY, Baptiste C, Hombalegowda RB, Tergas AI, Feldman R, Jones NL, et al. Vulvar and vaginal melanoma: a unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma. Cancer. 2017;123:1333–44.
pubmed: 28026870
doi: 10.1002/cncr.30473
Saleh B, Kriegsmann J, Falk S, Aulmann S. Frequent PD-L1 Expression in Malignant Melanomas of the Vulva. Int J Gynecol Pathol. 2018;37:477–81.
pubmed: 28914674
doi: 10.1097/PGP.0000000000000454
Kaunitz GJ, Cottrell TR, Lilo M, Muthappan V, Esandrio J, Berry S, et al. Melanoma subtypes demonstrate distinct PD-L1 expression profiles. Lab Invest. 2017;97:1063–71.
pubmed: 28737763
pmcid: 5685163
doi: 10.1038/labinvest.2017.64
Chłopik A, Selim MA, Peng Y, Wu C-L, Tell-Marti G, Paral KM, et al. Prognostic role of tumoral PDL1 expression and peritumoral FoxP3+ lymphocytes in vulvar melanomas. Hum Pathol. 2018;73:176–83.
pubmed: 29307625
doi: 10.1016/j.humpath.2017.12.022
Shoushtari AN, Munhoz RR, Kuk D, Ott PA, Johnson DB, Tsai KK, et al. The efficacy of anti‐PD‐1 agents in acral and mucosal melanoma. Cancer. 2016;122:3354–62.
pubmed: 27533633
pmcid: 5134420
doi: 10.1002/cncr.30259
Alvino E, Passarelli F, Cannavò E, Fortes C, Mastroeni S, Caporali S, et al. High expression of the mismatch repair protein MSH6 is associated with poor patient survival in melanoma. Am J Clin Pathol. 2014;142:121–32.
pubmed: 24926095
doi: 10.1309/AJCPCX2D9YULBBLG
Lee WJ, Lee YJ, Shin HJ, Won CH, Chang SE, Choi JH, et al. Clinicopathological significance of tumor-infiltrating lymphocytes and programmed death-1 expression in cutaneous melanoma: a comparative study on clinical subtypes. Melanoma Res. 2018;28:423–34.
pubmed: 29634635
Kluger H, Zito CR, Barr M, Baine M, Chiang VL, Sznol M, et al. Characterization of PD-L1 expression and associated T cell infiltrates in metastatic melanoma samples from variable anatomic sites. Clin Cancer Res. 2015;12:3052–60.
doi: 10.1158/1078-0432.CCR-14-3073
Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015;75:2139–45.
pubmed: 25977340
pmcid: 4452411
doi: 10.1158/0008-5472.CAN-15-0255
Taube JM, Klein AP, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20:5064–74.
pubmed: 24714771
pmcid: 4185001
doi: 10.1158/1078-0432.CCR-13-3271
Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.
pubmed: 28596308
pmcid: 5576142
doi: 10.1126/science.aan6733
Kubeček O, Kopecký J. Microsatellite instability in melanoma: a comprehensive review. Melanoma Res. 2016;26:545–50.
pubmed: 27623135
doi: 10.1097/CMR.0000000000000298
Castiglia D, Bernardini S, Alvino E, Pagani E, De Luca N, Falcinelli S, et al. Concomitant activation of Wnt pathway and loss of mismatch repair function in human melanoma. Genes Chromosomes Cancer. 2008;47:614–24.
pubmed: 18384130
doi: 10.1002/gcc.20567
Palmieri G, Ascierto PA, Cossu A, Colombino M, Casula M, Botti G, et al. Assessment of genetic instability in melanocytic skin lesions through microsatellite analysis of benign naevi, dysplastic naevi, and primary melanomas and their metastases. Melanoma Res. 2003;13:167–70.
pubmed: 12690300
doi: 10.1097/00008390-200304000-00009
Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26:3279–90.
pubmed: 17496922
doi: 10.1038/sj.onc.1210421
van Engen-van Grunsven AC, Küsters-Vandevelde HV, De Hullu J, van Duijn LM, Rijntjes J, Bovée JV, et al. NRAS mutations are more prevalent than KIT mutations in melanoma of the female urogenital tract—a study of 24 cases from the Netherlands. Gynecol Oncol. 2014;134:10–4.
pubmed: 24802725
doi: 10.1016/j.ygyno.2014.04.056
Tseng D, Kim J, Warrick A, Nelson D, Pukay M, Beadling C, et al. Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract. J Am Acad Dermatol. 2014;71:229–36.
pubmed: 24842760
pmcid: 4450888
doi: 10.1016/j.jaad.2014.03.033
Ponti G, Manfredini M, Greco S, Pellacani G, Depenni R, Tomasi A, et al. BRAF, NRAS and C-KIT advanced melanoma: clinico-pathological features, targeted-therapy strategies and survival. Anticancer Res. 2017;37:7043–8.
pubmed: 29187493
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;37:61–5.
pubmed: 23026937
doi: 10.1097/PAS.0b013e31826485c0
Wong CW, Fan YS, Chan TL, Chan AS, Ho LC, Ma TK, et al. BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs. J Clin Pathol. 2005;58:640–4.
pubmed: 15917418
pmcid: 1770697
doi: 10.1136/jcp.2004.022509
Aulmann S, Sinn HP, Penzel R, Gilks CB, Schott S, Hassel JC, et al. Comparison of molecular abnormalities in vulvar and vaginal melanomas. Mod Pathol. 2014;27:1386–93.
pubmed: 24603591
doi: 10.1038/modpathol.2013.211
Seifried S, Haydu LE, Quinn MJ, Scolyer RA, Stretch JR, Thompson JF. Melanoma of the vulva and vagina: principles of staging and their relevance to management based on a clinicopathologic analysis of 85 cases. Ann Surg Oncol. 2015;22:1959–66.
pubmed: 25384702
doi: 10.1245/s10434-014-4215-3
Piura B. Management of primary melanoma of the female urogenital tract. Lancet Oncol. 2008;9:973–81.
pubmed: 19071254
doi: 10.1016/S1470-2045(08)70254-7
Stamatelli A, Saetta AA, Bei T, Kavantzas N, Michalopoulos NV, Patsouris E, et al. B-Raf mutations, microsatellite instability and p53 protein expression in sporadic basal cell carcinomas. Pathol Oncol Res. 2011;17:633–7.
pubmed: 21274671
doi: 10.1007/s12253-011-9363-1
Vaysse C, Pautier P, Filleron T, Maisongrosse V, Rodier J-F, Lavoue V, et al. A large retrospective multicenter study of vaginal melanomas: implications for new management. Melanoma Res. 2013;23:138–46.
pubmed: 23449321
doi: 10.1097/CMR.0b013e32835e590e
Haiducu ML, Hinek A, Astanehe A, Lee TK, Kalia S. Extracutaneous melanoma epidemiology in British Columbia. Melanoma Res. 2014;24:377–80.
pubmed: 24722196
doi: 10.1097/CMR.0000000000000075
Üzüm N, Köse F, Ataoğlu Ö. Metastatic malignant melanoma of the uterine cervix: First diagnosed on liquid‐based cytology. Diagn Cytopathol. 2008;36:769–72.
pubmed: 18831038
doi: 10.1002/dc.20917
Deshpande AH, Munshi MM. Primary malignant melanoma of the uterine cervix: report of a case diagnosed by cervical scrape cytology and review of the literature. Diagn Cytopathol. 2001;25:108–11.
pubmed: 11477714
doi: 10.1002/dc.2014
Lee JH, Yun J, Seo J-W, Bae G-E, Lee J-W, Kim SW. Primary malignant melanoma of cervix and vagina. Obstet Gynecol Sci. 2016;59:415–20.
pubmed: 27668208
pmcid: 5028652
doi: 10.5468/ogs.2016.59.5.415
Frumovitz M, Etchepareborda M, Sun CC, Soliman PT, Eifel PJ, Levenback CF, et al. Primary malignant melanoma of the vagina. Obstet Gynecol. 2010;116:1358–65.
pubmed: 21099603
doi: 10.1097/AOG.0b013e3181fb8045
Cobellis L, Calabrese E, Stefanon B, Raspagliesi F. Malignant melanoma of the vagina. A report of 15 cases. Eur J Gynaecol Oncol. 2000;21:295–7.
pubmed: 10949399
Udager AM, Frisch NK, Hong LJ, Stasenko M, Johnston CM, Liu JR, et al. Gynecologic melanomas: A clinicopathologic and molecular analysis. Gynecol Oncol. 2017;147:351–7.
pubmed: 28844540
doi: 10.1016/j.ygyno.2017.08.023
Ditto A, Bogani G, Martinelli F, Di Donato V, Laufer J, Scasso S, et al. Surgical management and prognostic factors of vulvovaginal melanoma. J Low Genit Trac Dis. 2016;20:e24–e9.
doi: 10.1097/LGT.0000000000000204
Miner TJ, Delgado R, Zeisler J, Busam K, Alektiar K, Barakat R, et al. Primary vaginal melanoma: a critical analysis of therapy. Ann Surg Oncol. 2004;11:34–9.
pubmed: 14699031
doi: 10.1007/BF02524343
Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Spatz A, et al. Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline–Update 2012. Eur J Cancer. 2012;48:2375–90.
pubmed: 22981501
doi: 10.1016/j.ejca.2012.06.013
Ditto A, Bogani G, Martinelli F, Raspagliesi F. Treatment of genital melanoma: are we ready for innovative therapies? Int J Gynecol Cancer. 2017;27:1063.
pubmed: 30814192
doi: 10.1097/IGC.0000000000001018
Wong SL, Balch CM, Hurley P, Agarwala SS, Akhurst TJ, Cochran A, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. Ann Surg Oncol. 2012;19:3313–24.
pubmed: 22766987
doi: 10.1245/s10434-012-2475-3
Janco JMT, Markovic SN, Weaver AL, Cliby WA. Vulvar and vaginal melanoma: case series and review of current management options including neoadjuvant chemotherapy. Gynecol Oncol. 2013;129:533–7.
pubmed: 23480869
doi: 10.1016/j.ygyno.2013.02.028
Harting MS, Kim KB. Biochemotherapy in patients with advanced vulvovaginal mucosal melanoma. Melanoma Res. 2004;14:517–20.
pubmed: 15577323
doi: 10.1097/00008390-200412000-00012
Serrone L, Zeuli M, Sega F, Cognetti F. Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res. 2000;19:21–34.
pubmed: 10840932
Saito T, Tabata T, Ikushima H, Yanai H, Tashiro H, Niikura H, et al. Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer. Int J Clin Oncol. 2018;23:201–34.
pubmed: 29159773
doi: 10.1007/s10147-017-1193-z
Schiavone MB, Broach V, Shoushtari AN, Carvajal RD, Alektiar K, Kollmeier MA, et al. Combined immunotherapy and radiation for treatment of mucosal melanomas of the lower genital tract. Gynecol Oncol Rep. 2016;16:42–6.
pubmed: 27331137
pmcid: 4899413
doi: 10.1016/j.gore.2016.04.001
Lipson EJ, Forde PM, Hammers HJ, Emens LA, Taube JM, Topalian SL. Antagonists of PD-1 and PD-L1 in Cancer Treatment. Semin Oncol. 2015;42:587–600.
pubmed: 26320063
pmcid: 4555873
doi: 10.1053/j.seminoncol.2015.05.013
Sunshine J, Taube JM. PD-1/PD-L1 inhibitors. Curr Opin Pharmacol. 2015;23:32–8.
pubmed: 26047524
pmcid: 4516625
doi: 10.1016/j.coph.2015.05.011
Daud AI, Wolchok JD, Robert C, Hwu W-J, Weber JS, Ribas A, et al. Programmed death-ligand 1 expression and response to the anti–programmed death 1 antibody Pembrolizumab in melanoma. J Clin Oncol. 2016;34:4102.
pubmed: 27863197
pmcid: 5562434
doi: 10.1200/JCO.2016.67.2477
Hino R, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T, et al. Tumor cell expression of programmed cell death‐1 ligand 1 is a prognostic factor for malignant melanoma. Cancer. 2010;116:1757–66.
pubmed: 20143437
doi: 10.1002/cncr.24899
Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14:847–56.
pubmed: 25695955
doi: 10.1158/1535-7163.MCT-14-0983
Chan AWH, Tong JHM, Kwan JSH, Chow C, Chung LY, Chau SL, et al. Assessment of programmed cell death ligand-1 expression by 4 diagnostic assays and its clinicopathological correlation in a large cohort of surgical resected non-small cell lung carcinoma. Mod Pathol. 2018;31:1381–90.
pubmed: 29713040
doi: 10.1038/s41379-018-0053-3
Sunshine JC, Nguyen PL, Kaunitz GJ, Cottrell TR, Berry S, Esandrio J, et al. PD-L1 Expression in Melanoma: A Quantitative Immunohistochemical Antibody Comparison. Clin Cancer Res. 2017;23:4938–44.
pubmed: 28428193
pmcid: 6175606
doi: 10.1158/1078-0432.CCR-16-1821
Kerr KM, Hirsch FR. Programmed Death Ligand-1 Immunohistochemistry: Friend or Foe? Arch Pathol Lab Med. 2016;140:326–31.
pubmed: 26756647
doi: 10.5858/arpa.2015-0522-SA
Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, et al. PD-L1 Immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol. 2017;12:208–22.
pubmed: 27913228
doi: 10.1016/j.jtho.2016.11.2228
D’Angelo SP, Larkin J, Sosman JA, Lebbe C, Brady B, Neyns B, et al. Efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with mucosal melanoma: a pooled analysis. J Clin Oncol. 2017;35:226–35.
pubmed: 28056206
doi: 10.1200/JCO.2016.67.9258
Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.
pubmed: 25891173
doi: 10.1056/NEJMoa1503093
Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017;377:1824–35.
pubmed: 28891423
doi: 10.1056/NEJMoa1709030
Quereux G, Wylomanski S, Bouquin R, Saint-Jean M, Peuvrel L, Knol AC, et al. Are checkpoint inhibitors a valuable option for metastatic or unresectable vulvar and vaginal melanomas? J Eur Acad Dermatol Venereol. 2018;32:e39–e40.
pubmed: 28750150
doi: 10.1111/jdv.14486
Fridman WH, Galon J, Pagès F, Tartour E, Sautès-Fridman C, Kroemer G. Prognostic and predictive impact of intra-and peritumoral immune infiltrates. Cancer Res. 2011;71:5601–5.
pubmed: 21846822
doi: 10.1158/0008-5472.CAN-11-1316
Azimi F, Scolyer RA, Rumcheva P, Moncrieff M, Murali R, McCarthy SW, et al. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol. 2012;30:2678–83.
pubmed: 22711850
doi: 10.1200/JCO.2011.37.8539
Saldanha G, Flatman K, Teo KW, Bamford M. A novel numerical scoring system for melanoma tumor-infiltrating lymphocytes has better prognostic value than standard scoring. Am J Surg Pathol. 2017;41:906–14.
pubmed: 28368925
pmcid: 6171741
doi: 10.1097/PAS.0000000000000848
Koelzer VH, Sirinukunwattana K, Rittscher J, Mertz KD. Precision immunoprofiling by image analysis and artificial intelligence. Virchows Arch 2019;474:511–22.
pubmed: 30470933
doi: 10.1007/s00428-018-2485-z
Yu K, Liu X, Jiang Z, Hu C, Zou F, Chen C, et al. Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for gastrointestinal stromal tumors (GISTs). Oncotarget. 2017;8:111110–8.
pubmed: 29340041
pmcid: 5762309
Gajiwala KS, Wu JC, Christensen J, Deshmukh GD, Diehl W, DiNitto JP, et al. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci USA. 2009;106:1542–7.
pubmed: 19164557
doi: 10.1073/pnas.0812413106
Noujaim J, Gonzalez D, Thway K, Jones RL, Judson I. p.(L576P)-KIT mutation in GIST: Favorable prognosis and sensitive to imatinib? Cancer Biol Ther. 2016;17:543–5.
pubmed: 26942271
pmcid: 4910923
doi: 10.1080/15384047.2016.1156263
Nishida T, Kanda T, Nishitani A, Takahashi T, Nakajima K, Ishikawa T, et al. Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib‐resistant gastrointestinal stromal tumor. Cancer Sci. 2008;99:799–804.
pubmed: 18294292
doi: 10.1111/j.1349-7006.2008.00727.x
Roberts KG, Odell AF, Byrnes EM, Baleato RM, Griffith R, Lyons AB, et al. Resistance to c-KIT kinase inhibitors conferred by V654A mutation. Mol Cancer Ther 2007;6:1159–66.
pubmed: 17363509
doi: 10.1158/1535-7163.MCT-06-0641
Spitaleri G, Biffi R, Barberis M, Fumagalli C, Toffalorio F, Catania C, et al. Inactivity of imatinib in gastrointestinal stromal tumors (GISTs) harboring a KIT activation-loop domain mutation (exon 17 mutation pN822K). OncoTargets Ther. 2015;8:1997.
doi: 10.2147/OTT.S81558
Ma Y, Cunningham ME, Wang X, Ghosh I, Regan L, Longley BJ. Inhibition of spontaneous receptor phosphorylation by residues in a putative α-helix in the KIT intracellular juxtamembrane region. J Biol Chem. 1999;274:13399–402.
pubmed: 10224103
doi: 10.1074/jbc.274.19.13399
Curtin JA, Busam K, Pinkel D, Bastian BC. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24:4340–6.
pubmed: 16908931
doi: 10.1200/JCO.2006.06.2984
Rossi S, Gasparotto D, Toffolatti L, Pastrello C, Gallina G, Marzotto A, et al. Molecular and clinicopathologic characterization of gastrointestinal stromal tumors (GISTs) of small size. Am J Surg Pathol. 2010;34:1480–91.
pubmed: 20861712
doi: 10.1097/PAS.0b013e3181ef7431
Shain AH, Garrido M, Botton T, Talevich E, Yeh I, Sanborn JZ, et al. Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway. Nat Genet. 2015;47:1194.
pubmed: 26343386
pmcid: 4589486
doi: 10.1038/ng.3382
Kong Y, Si L, Zhu Y, Xu XG, Corless CL, Flaherty K, et al. Large scale analysis of KIT aberrations in Chinese patients with melanoma. Clin Cancer Res. 2011;17:1684–91. clincanres. 2346.010
pubmed: 21325067
doi: 10.1158/1078-0432.CCR-10-2346
Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Mod Pathol. 2018;31:24–38.
pubmed: 29148538
doi: 10.1038/modpathol.2017.104
Pappa KI, Vlachos GD, Roubelakis M, Vlachos D-EG, Kalafati TG, Loutradis D, et al. Low mutational burden of eight genes involved in the MAPK/ERK, PI3K/AKT, and GNAQ/11 pathways in female genital tract primary melanomas. Biomed Res Int. 2015;2015:303791.
pubmed: 25695059
pmcid: 4324736
doi: 10.1155/2015/303791
Wylomanski S, Denis MG, Theoleyre S, Bouquin R, Vallee A, Knol AC, et al. BRAF mutations might be more common than supposed in vulvar melanomas. Exp Dermatol. 2018;27:210–3.
pubmed: 29178146
doi: 10.1111/exd.13472
Anwar MA, Murad F, Dawson E, Abd Elmageed ZY, Tsumagari K, Kandil E. Immunohistochemistry as a reliable method for detection of BRAF-V600E mutation in melanoma: a systematic review and meta-analysis of current published literature. J Surg Res. 2016;203:407–15.
pubmed: 27363650
doi: 10.1016/j.jss.2016.04.029
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;41:724–32.
pubmed: 24917033
pmcid: 4167935
doi: 10.1111/cup.12364
Naboush A, Roman CA, Shapira I. Immune checkpoint inhibitors in malignancies with mismatch repair deficiency: a review of the state of the current knowledge. J Invest Med. 2017;65:754–8.
doi: 10.1136/jim-2016-000342
Roncati L. Microsatellite instability predicts response to anti-PD1 immunotherapy in metastatic melanoma. Acta Derm Croat. 2018;26:341–3.