Clinical significance of BRAF V600E mutational status in capsular nevi of sentinel lymph nodes in patients with primary cutaneous melanoma.
Capsular nevi (CN) are clusters of benign melanocytes situated in the capsule of lymph nodes and occur in up to 20% of lympadenectomy specimens. The molecular profile of CN in relation to prognostic parameters in patients with primary cutaneous melanoma (PCM) has not been previously investigated. We assessed BRAF V600E mutation by immunohistochemistry (IHC) in the CN of sentinel lymph nodes (SLN) in PCM patients and correlated the findings with demographic characteristics, PCM histopathologic and molecular features, and clinical outcome parameters. Seventy-eight cases of CN involving SLN of PCM patients were evaluated for BRAF V600E mutation by IHC. The results were correlated with patient demographics, PCM histopathologic and molecular features, and outcome measures. Thirty-six (46%) of 78 CN cases expressed BRAF V600E mutation by IHC. Nineteen (53%) of those BRAF-positive CN cases were from patients with at least American Joint Committee on Cancer stage II melanoma, whereas 62% of BRAF-negative CN cases (26/42) were from patients with stage I melanoma (P = .013). Twelve (33%) of the 36 BRAF-positive CN cases had metastatic melanoma involving lymph nodes, compared with 14% (6/42) of BRAF-negative CN cases (P = .061). CN mutation status was not associated with patient demographics, histopathologic or molecular features of the PCM, or survival outcomes. A high percentage of CN identified in the SLN of patients with PCM harbor BRAF V600E mutation. Positive mutation was associated with adverse clinicopathological parameters, specifically increased tumor stage and lymph node metastasis. These findings suggest that BRAF V600E mutation in CN of SLN may be useful as an adverse predictive biomarker in patients with melanoma.
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Alan E
AE
Siroy
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Phyu P
PP
Aung
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030; Department of Dermatology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Carlos A
CA
Torres-Cabala
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Michael T
MT
Tetzlaff
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Priyadharsini
P
Nagarajan
Department of Biostatistics, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Denái R
DR
Milton
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030; Department of Dermatology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Jonathan L
JL
Curry
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030; Department of Dermatology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030.
Doina
D
Ivan
Department of Pathology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030; Department of Dermatology, The University of Texas-MD Anderson Cancer Center, Houston, TX 77030. Electronic address: vprieto@mdanderson.org.
Victor G
VG
Prieto
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008544:Melanocytes / Q000473:pathology*; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D055815:Young Adult
D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
BRAF mutation; Capsular nevus; Immunohistochemistry; Melanoma; Sentinel lymph node