TY - JOUR
T1 - Distinctive clinical and histologic features in cutaneous melanoma with copy number gains in 8q24
AU - Pouryazdanparast, Pedram
AU - Cowen, D. Patrick
AU - Beilfuss, Beth Ann
AU - Haghighat, Zahra
AU - Guitart, Joan
AU - Rademaker, Alfred
AU - Gerami, Pedram
PY - 2012/2
Y1 - 2012/2
N2 - Cutaneous melanoma may be quite heterogeneous in its clinical, histologic, and molecular features. Yet, the current classification of melanoma is limited to 4 main subtypes on the basis of clinical and histopathologic features and has shown limited impact on clinical management including prognostication and treatment. Advances in our understanding of the driving molecular pathways in melanoma and the importance of the mitogen-activated protein kinase pathway have shown that specific activating mutations in oncogenes may correlate with characteristic clinical and histologic features. We evaluated 40 melanoma cases with gains in MYC at 8q24, and we show that their characteristic features include aggressive clinical course, occurrence in nonchronically sun-damaged skin, amelanotic clinical and histopathologic appearance, a nodular or primary dermal growth pattern by histology, frequent epidermal consumption, and infrequent association with a precursor nevus. The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) mutation status was also determined. The presence of these mutations was comparable to frequencies previously reported from nonchronically sun-damaged skin. However, the BRAF mutant cases did not show histopathologic features considered characteristic of BRAF mutant melanoma. Considering these distinct clinical and histopathologic features and the possible role as a theragnostic tool, it may be of value to consider 8q24 status in cutaneous melanoma in addition to the mutation status of BRAF in future studies integrating molecular findings into the classification system for cutaneous melanoma.
AB - Cutaneous melanoma may be quite heterogeneous in its clinical, histologic, and molecular features. Yet, the current classification of melanoma is limited to 4 main subtypes on the basis of clinical and histopathologic features and has shown limited impact on clinical management including prognostication and treatment. Advances in our understanding of the driving molecular pathways in melanoma and the importance of the mitogen-activated protein kinase pathway have shown that specific activating mutations in oncogenes may correlate with characteristic clinical and histologic features. We evaluated 40 melanoma cases with gains in MYC at 8q24, and we show that their characteristic features include aggressive clinical course, occurrence in nonchronically sun-damaged skin, amelanotic clinical and histopathologic appearance, a nodular or primary dermal growth pattern by histology, frequent epidermal consumption, and infrequent association with a precursor nevus. The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) mutation status was also determined. The presence of these mutations was comparable to frequencies previously reported from nonchronically sun-damaged skin. However, the BRAF mutant cases did not show histopathologic features considered characteristic of BRAF mutant melanoma. Considering these distinct clinical and histopathologic features and the possible role as a theragnostic tool, it may be of value to consider 8q24 status in cutaneous melanoma in addition to the mutation status of BRAF in future studies integrating molecular findings into the classification system for cutaneous melanoma.
KW - BRAF
KW - Fluorescence in situ hybridization
KW - MYC
KW - Melanoma
KW - Mutation
KW - NRAS
UR - http://www.scopus.com/inward/record.url?scp=84857743726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857743726&partnerID=8YFLogxK
U2 - 10.1097/PAS.0b013e31823425cc
DO - 10.1097/PAS.0b013e31823425cc
M3 - Article
C2 - 22020039
AN - SCOPUS:84857743726
SN - 0147-5185
VL - 36
SP - 253
EP - 264
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 2
ER -