Napsin A、α-甲基酰基辅酶A消旋酶（AMACR，P504S）和肝细胞核因子1β作为卵巢透明细胞癌诊断标志物的比较分析：279例卵巢肿瘤的免疫组织化学研究
Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase (AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma: an immunohistochemical study of 279 ovarian tumours.
作者信息
Fadare Oluwole, Zhao Chengquan, Khabele Dineo, Parkash Vinita, Quick Charles M, Gwin Katja, Desouki Mohamed M
机构信息
1Department of Pathology, University of California San Diego, San Diego, CA 2Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 3Departments of Obstetrics and Gynecology, and of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 4Department of Pathology, Yale University School of Medicine, New Haven, CT 5Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 6Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 7Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN, United States.
出版信息
Pathology. 2015 Feb;47(2):105-11. doi: 10.1097/PAT.0000000000000223.
Napsin A and α-methylacyl-coenzyme A racemase (AMACR, P504S) have recently been described as being frequently expressed in clear cell carcinomas (CCC) of the gynecological tract. The present study was conducted to assess the test performance of these newer markers relative to the more traditional marker, hepatocyte nuclear factor 1β (HNF1β), in a large and histotypically diverse dataset. A total of 279 ovarian tumours in tissue microarrays were immunohistochemically assessed for the expression of Napsin A, AMACR and HNF1β. HNF1β, Napsin A and AMACR were expressed in 92%, 82% and 63% of 65 CCC, 7%, 1% and 1% of 101 serous carcinomas, 37%, 5.3% and 0% of 19 endometrioid carcinomas, 60%, 0% and 0% of 45 mucinous tumours, 100%, 0% and 0% of seven yolk sac tumours, and 0%, 16.7% and 16.7% of six steroid cell tumours NOS, respectively. All other tumours, including 18 adult-type granulosa cell tumours, eight dysgerminomas and nine other miscellaneous tumour types were negative for all three markers. Using a benchmark of ≥1% of tumour cells for positivity and CCC as the diagnostic end-point, the sensitivity, specificity, negative predictive value and positive predictive value of Napsin A expression were 0.82, 0.99, 0.94, and 0.98, respectively (odds ratio 439, p < 0.0001). Respective parameters were 0.92, 0.79, 0.97, and 0.58 (odds ratio 44, p < 0.0001) for HNF1β and 0.63, 0.99, 0.89, and 0.5 (odds ratio 112, p < 0.0001) for AMACR. The combination of any two positive markers, irrespective of the staining pattern of the third, significantly predicted the CCC histotype in every analytic scenario. In summary, HNF1β is highly sensitive but is suboptimally specific in isolation, whereas AMACR is highly specific but is suboptimally sensitive. Napsin A is specific but of intermediate sensitivity. Napsin A, AMACR and HNF1β are all viable markers of CCC that can be deployed as components of larger panels when CCC is a diagnostic consideration.
最近研究发现，Napsin A和α-甲基酰基辅酶A消旋酶（AMACR，P504S）常表达于妇科透明细胞癌（CCC）中。本研究旨在评估这些新型标志物相对于更传统的标志物——肝细胞核因子1β（HNF1β）在一个大型且组织学类型多样的数据集中的检测性能。对组织芯片中的279例卵巢肿瘤进行免疫组织化学分析，检测Napsin A、AMACR和HNF1β的表达情况。在65例CCC中，HNF1β、Napsin A和AMACR的表达率分别为92%、82%和63%；在101例浆液性癌中，表达率分别为7%、1%和1%；在19例子宫内膜样癌中，表达率分别为37%、5.3%和0%；在45例黏液性肿瘤中，表达率分别为60%、0%和0%；在7例卵黄囊瘤中，表达率分别为100%、0%和0%；在6例未分类的类固醇细胞瘤中，表达率分别为0%、16.7%和16.7%。所有其他肿瘤，包括18例成人型颗粒细胞瘤、8例无性细胞瘤和9种其他杂类肿瘤类型，这三种标志物的表达均为阴性。以肿瘤细胞阳性率≥1%为阳性标准，以CCC为诊断终点，Napsin A表达的敏感性、特异性、阴性预测值和阳性预测值分别为0.82、0.99、0.94和0.98（优势比439，p<0.0001）。HNF1β的相应参数分别为0.92、0.79、0.97和0.58（优势比44，p<0.0001），AMACR的相应参数分别为0.63、0.99、0.89和0.5（优势比112，p<0.0001）。在每种分析情况下，任意两种阳性标志物的组合，无论第三种标志物的染色模式如何，都能显著预测CCC组织学类型。总之，HNF1β敏感性高，但单独使用时特异性欠佳；而AMACR特异性高，但敏感性欠佳。Napsin A具有特异性，但敏感性中等。当考虑诊断CCC时，Napsin A、AMACR和HNF1β都是可行的CCC标志物，可作为更大检测组合的组成部分使用。
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