Latchana Nicholas, Regan Kelly, Howard J Harrison, Aldrink Jennifer H, Ranalli Mark A, Peters Sara B, Zhang Xiaoli, Gru Alejandro, Payne Philip R O, Suarez-Kelly Lorena P, Carson William E
Division of Surgical Oncology, Department of Surgery, The Ohio State University, Columbus, OH.
Department of Biomedical Informatics, The Ohio State University, Columbus, OH.
J Surg Res. 2016 Oct;205(2):350-358. doi: 10.1016/j.jss.2016.06.085. Epub 2016 Jul 4.
Melanoma skin cancer remains the leading cause of skin cancer-related deaths. Spitz lesions represent a subset of melanocytic skin lesions characterized by epithelioid or spindled melanocytes organized in nests. These lesions occupy a spectrum ranging from benign Spitz and atypical Spitz lesions all the way to malignant Spitz tumors. Appropriate management is reliant on accurate diagnostic classification, yet this effort remains challenging using current light microscopic techniques. The discovery of novel biomarkers such as microRNAs (miR) may ultimately be a useful diagnostic adjunct for the evaluation of Spitz lesions. miR expression profiles have been suggested for non-Spitz melanomas but have yet to be ascribed to Spitz lesions. We hypothesized that distinct miR expression profiles would be associated with different lesions along the Spitz spectrum.
RNAs extracted from paraffin-embedded, formalin-fixed tissues of 11 resected skin lesions including benign nevi (n = 2), benign Spitz lesions (n = 3), atypical Spitz lesions (n = 3), and malignant Spitz tumors (n = 3) were analyzed by the NanoString platform for simultaneous evaluation of over 800 miRs in each patient sample.
Benign Spitz lesions had increased expression of miR-21-5p and miR-363-3p compared with those of benign nevi. Malignant Spitz lesions exhibited overexpression of miR-21-5p, miR-155-5p, and miR-1283 relative to both benign nevi and benign Spitz tumors. Notably, atypical Spitz tumors had increased expression of miR-451a and decreased expression of miR-155-5p expression relative to malignant Spitz lesions. Conversely, atypical Spitz lesions had increased expression of miR-21-5p, miR-34a-5p, miR-451a, miR-1283, and miR-1260a relative to benign Spitz tumors.
Overall, distinct miR profiles are suggested among Spitz lesions of varying malignant potential with some similarities to non-Spitz melanoma tumors. This work demonstrates the feasibility of this analytic method and forms the basis for further validation studies.
皮肤黑色素瘤仍然是皮肤癌相关死亡的主要原因。斯皮茨病变是黑素细胞性皮肤病变的一个子集，其特征是上皮样或梭形黑素细胞呈巢状排列。这些病变涵盖了从良性斯皮茨病变和非典型斯皮茨病变到恶性斯皮茨肿瘤的一系列范围。恰当的处理依赖于准确的诊断分类，但使用当前的光学显微镜技术进行这项工作仍然具有挑战性。诸如微小RNA（miR）等新型生物标志物的发现最终可能成为评估斯皮茨病变的有用诊断辅助手段。已有研究提出非斯皮茨黑色素瘤的miR表达谱，但尚未将其归因于斯皮茨病变。我们假设不同的miR表达谱与斯皮茨病变谱中的不同病变相关。
从11例切除的皮肤病变的石蜡包埋、福尔马林固定组织中提取RNA，这些病变包括良性痣（n = 2）、良性斯皮茨病变（n = 3）、非典型斯皮茨病变（n = 3）和恶性斯皮茨肿瘤（n = 3），通过NanoString平台进行分析，以同时评估每个患者样本中的800多种miR。
与良性痣相比，良性斯皮茨病变中miR-21-5p和miR-363-3p的表达增加。相对于良性痣和良性斯皮茨肿瘤，恶性斯皮茨病变中miR-21-5p、miR-155-5p和miR-1283表达上调。值得注意的是，相对于恶性斯皮茨病变，非典型斯皮茨肿瘤中miR-451a表达增加，miR-155-5p表达降低。相反，相对于良性斯皮茨肿瘤，非典型斯皮茨病变中miR-21-5p、miR-34a-5p、miR-451a、miR-1283和miR-1260a表达增加。
总体而言，不同恶性潜能的斯皮茨病变中存在不同的miR谱，与非斯皮茨黑色素瘤肿瘤有一些相似之处。这项工作证明了这种分析方法的可行性，并为进一步的验证研究奠定了基础。
