Mudhar Hardeep Singh, Milman Tatyana, Stevenson Sarah, Watson Mark, Kim Julie, Magan Tejal, Salvi Sachin M, Harley Umiya, Lally Sarah E, Shields Carol L
National Specialist Ophthalmic Pathology Service (NSOPS), Dept of Histopathology, E-Floor, Royal Hallamshire Hospital, Sheffield S10 2JF, England, UK.
Department of Pathology, Wills Eye Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.
Hum Pathol. 2023 Apr;134:1-18. doi: 10.1016/j.humpath.2023.02.002. Epub 2023 Feb 16.
This study examined PRAME (preferentially expressed antigen in melanoma) expression by immunohistochemistry and reverse transcription quantitative PCR (RT-qPCR) in 202 histologically unequivocal conjunctival melanocytic lesions: 76 nevi, 29 benign melanoses, 25 low-grade conjunctival intraepithelial melanocytic lesions (LGCMIL), 26 high-grade conjunctival melanocytic intraepithelial lesions/in-situ melanoma (HGCMIL), and 46 invasive melanomas. PRAME score 0 was seen in 96% of nevi (73/76), 96% of benign melanoses (28/29), and 88% of LGCMIL (22/25). PRAME score 4 was seen in 50% HGCMIL (13/26) and 76% invasive melanomas (35/46). PRAME score 4 had a sensitivity of 50% and specificity of 100% in differentiating between HGCMIL and benign melanosis/LGCMIL. PRAME score 4 had a sensitivity of 76% and specificity of 100% in differentiating between melanoma and nevi. Relative quantification of PRAME mRNA expression by RT-qPCR was performed on 49 cases (24%): 17 nevi, 3 benign melanoses, 5 LGCMIL, 9 HGCMIL, and 15 invasive melanomas. The analysis generated two distinct groupings with 'high' relative PRAME expression for the HGCMIL and invasive melanoma and 'low/zero' expression for nevi, benign melanosis, and LGCMIL. Thirty-three challenging conjunctival melanocytic lesions that had previous fluorescence in situ hybridization (FISH) analysis were studied: 18 nevi, 12 melanomas in a nevus, 2 nevoid melanomas, and 1 in-situ melanoma. All nevi (100%) showed concordance between negative FISH and PRAME (scores 0-3). Four of 13 melanomas (31%; in-situ, invasive, isolated, and in association with nevus) showed concordance between positive FISH and PRAME score 4. In conclusion, PRAME score 4 has 100% specificity for the diagnosis of HGCMIL and melanoma. PRAME is limited in its sensitivity in the evaluation of challenging melanocytic lesions.
本研究通过免疫组织化学和逆转录定量聚合酶链反应（RT-qPCR）检测了202例组织学诊断明确的结膜黑素细胞性病变中PRAME（黑色素瘤中优先表达的抗原）的表达情况，这些病变包括76例痣、29例良性黑素沉着、25例低度结膜上皮内黑素细胞性病变（LGCMIL）、26例高度结膜黑素细胞上皮内病变/原位黑色素瘤（HGCMIL）以及46例浸润性黑色素瘤。96%的痣（73/76）、96%的良性黑素沉着（28/29）以及88%的LGCMIL（22/25）的PRAME评分为0。50%的HGCMIL（13/26）和76%的浸润性黑色素瘤（35/46）的PRAME评分为4。PRAME评分为4在区分HGCMIL与良性黑素沉着/LGCMIL时，敏感性为50%，特异性为100%。PRAME评分为4在区分黑色素瘤与痣时，敏感性为76%，特异性为100%。对49例病例（24%）进行了RT-qPCR法检测PRAME mRNA表达的相对定量分析，这些病例包括17例痣、3例良性黑素沉着、5例LGCMIL、9例HGCMIL以及15例浸润性黑色素瘤。分析产生了两个不同的分组，HGCMIL和浸润性黑色素瘤的PRAME相对表达为“高”，而痣、良性黑素沉着和LGCMIL的表达为“低/零”。对33例曾进行过荧光原位杂交（FISH）分析的具有挑战性的结膜黑素细胞性病变进行了研究，包括18例痣、12例痣内黑色素瘤、2例痣样黑色素瘤以及1例原位黑色素瘤。所有痣（100%）的FISH结果为阴性与PRAME（评分为0 - 3）结果一致。13例黑色素瘤中的4例（31%；原位、浸润性、孤立性以及与痣相关的）FISH结果为阳性与PRAME评分为4一致。总之，PRAME评分为4对HGCMIL和黑色素瘤的诊断具有100%的特异性。PRAME在评估具有挑战性的黑素细胞性病变时敏感性有限。
