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
Department of Surgery, The Ohio State University, Columbus, OH, USA.
Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Ann Surg Oncol. 2017 Feb;24(2):347-354. doi: 10.1245/s10434-016-5476-9. Epub 2016 Jul 28.
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.
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.
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.
miR expression profiles can be measured in indeterminate Spitz tumors and correlate with markers of malignant potential.
对可能发生肿瘤进展的不确定黑素细胞性皮肤病变进行识别的效果欠佳，可能会导致不必要的手术相关发病率。微小RNA（miR）可能有助于将不确定的Spitz肿瘤分类为具有高或低恶性行为风险。
从成人（n = 62）和儿童（n = 28）的良性痣、良性Spitz肿瘤、不确定的Spitz肿瘤和Spitz样黑色素瘤的石蜡包埋组织中提取RNA。通过实时聚合酶链反应分析12种miR在成人中的表达谱（儿童中为6种miR）。
与良性痣相比，良性Spitz病变的特征是miR-125b和miR-211表达降低，miR-22上调（p < 0.05）。Spitz样黑色素瘤与良性痣的比较显示，恶性原发灶中miR-21、miR-150和miR-155过表达（p < 0.05）。在成人中，Spitz样黑色素瘤与不确定的Spitz病变相比，miR-21、miR-150和miR-155上调。具有低风险病理特征的不确定Spitz病变与成人Spitz样黑色素瘤肿瘤相比，miR-21和miR-155表达较低（p < 0.05），而病理高风险的不确定Spitz病变与低风险不确定病变相比，miR-200c表达水平升高（p < 0.05）。儿童Spitz样黑色素瘤与不确定的Spitz病变相比，miR-21表达增加（p < 0.05）。此外，有丝分裂计数>1且浸润深度>1 mm的不确定病变中miR-155表达增加，提示miR-155表达与组织学特征相关。
可在不确定的Spitz肿瘤中测量miR表达谱，且其与恶性潜能标志物相关。
