Classification of Indeterminate Melanocytic Lesions by MicroRNA Profiling

• Published in: Annals of surgical oncology Vol. 24; no. 2; pp. 347 - 354
• Main Authors: Latchana, Nicholas, del Campo, Sara E. Martin, Grignol, Valerie P., Clark, Jennifer R., Albert, Scott P., Zhang, Jie, Wei, Lai, Aldrink, Jennifer H., Nicol, Kathleen K., Ranalli, Mark A., Peters, Sara B., Gru, Alejandro, Trihka, Prashant, Payne, Philip R. O., Howard, J. Harrison, Carson, William E.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-02-2017; Springer Nature B.V
• Subjects: Adult; Biomarkers, Tumor - genetics; Child; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Male; Medicine; Medicine & Public Health; Melanoma - classification; Melanoma - diagnosis; Melanoma - genetics; Melanomas; MicroRNAs - genetics; Nevus, Epithelioid and Spindle Cell - classification; Nevus, Epithelioid and Spindle Cell - diagnosis; Nevus, Epithelioid and Spindle Cell - genetics; Oncology; Prognosis; Skin Neoplasms - classification; Skin Neoplasms - diagnosis; Skin Neoplasms - genetics; Surgery; Surgical Oncology; Melanocytic Lesion; Sentinel Lymph Node Biopsy; Lymph Node Disease; Electronic Supplementary Table; Melanoma
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-016-5476-9

Purpose
Identification of indeterminate melanocytic skin lesions capable of neoplastic progression is suboptimal and may potentially result in unnecessary morbidity from surgery. MicroRNAs (miRs) may be useful in classifying indeterminate Spitz tumors as having high or low risk for malignant behavior.
Methods
RNA was extracted from paraffin-embedded tissues of benign nevi, benign Spitz tumors, indeterminate Spitz tumors, and Spitzoid melanomas in adults (
n
 = 62) and children (
n
 = 28). The expression profile of 12 miRs in adults (6 miRs in children) was analyzed by real-time polymerase chain reaction.
Results
Benign Spitz lesions were characterized by decreased expression of miR-125b and miR-211, and upregulation of miR-22, compared with benign nevi (
p
 < 0.05). A comparison of Spitzoid melanomas to benign nevi revealed overexpression of miR-21, miR-150, and miR-155 in the malignant primaries (
p
 < 0.05). In adults, Spitzoid melanomas exhibited upregulation of miR-21, miR-150, and miR-155 compared with indeterminate Spitz lesions. Indeterminate Spitz lesions with low-risk pathologic features had lower miR-21 and miR-155 expression compared with Spitzoid melanoma tumors in adults (
p
 < 0.05), while pathologic high-risk indeterminate Spitz lesions had increased levels of miR-200c expression compared with low-risk indeterminate lesions (
p
 < 0.05). Pediatric Spitzoid melanomas exhibited increased miR-21 expression compared with indeterminate Spitz lesions (
p
 < 0.05). Moreover, miR-155 expression was increased in indeterminate lesions with mitotic counts >1 and depth of invasion >1 mm, suggesting miR-155 expression is associated with histological characteristics.
Conclusions
miR expression profiles can be measured in indeterminate Spitz tumors and correlate with markers of malignant potential.