Departments of *Pathology, Microbiology and Immunology †Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN ‡Department of Pathology, University of Chicago, Chicago, IL §Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA ∥Department of Pathology, University of Utah School of Medicine and ARUP Laboratories, Salt Lake City, UT ¶Department of Pathology and Laboratory Medicine, North Shore-LIJ Health System and Hofstra North Shore-LIJ School of Medicine, New Hyde Park, NY #Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR Departments of **Pathology ††Obstetrics & Gynecology, University of Arizona College of Medicine, Tucson, AZ ‡‡Department of Pathology, Yale University School of Medicine, New Haven §§Department of Pathology, Bridgeport Hospital, Bridgeport, CT ∥∥Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2014 Feb;38(2):189-96. doi: 10.1097/PAS.0000000000000085.
The histotyping of high-grade endometrial carcinomas with clear cells may be subject to significant interobserver variability, which suggests that a biomarker that can distinguish endometrial clear cell carcinoma (CCC) from its mimics would be of diagnostic utility. This study assessed the usefulness of napsin A immunohistochemistry in the diagnosis of CCC, on the basis of an analysis of 77 cases diagnosed as such at 9 institutions. After being independently reviewed by a subset of 3 pathologists, cases for which there was diagnostic consensus among all 3 reviewers in agreement with the primary contributor (n=60) were used to establish a "consensus group" that served as a gold standard relative to which napsin A performance was assessed. Duplicate, 1.0-mm-core tissue microarrays were constructed from the 54 cases in the consensus group for which requisite materials were available, as well as from 49 endometrial endometrioid carcinomas (all grades) and 17 endometrial serous carcinomas. Napsin A immunohistochemical analysis was performed on the microarrays and on the 17 cases for which there was no diagnostic consensus, with scoring based on the proportion of immunoreactive cells (0, 1+, 2+, and 3+ indicative of 0, 1% to 25%, 26% to 49%, and ≥50% immunoreactive cells, respectively). The distribution of scores for the 49 CCC cases with evaluable cores was as follows: 0, n=6; 1+, n=6; 2+, n=8; 3+, n=29. Among the evaluable cases, the frequency of ≥1+ napsin A immunoreactivity was significantly higher in CCCs (43/49, 88%) than in endometrial serous carcinomas (1/13, 7.7%; P<0.0001) and endometrial endometrioid carcinomas (0/49, 0%; P<0.0001). The sensitivity, specificity, negative predictive value, and positive predictive value of ≥1+ napsin A expression in predicting the consensus clear cell histotype were 0.88 (95% confidence interval [CI], 0.75-0.95), 0.98 (95% CI, 0.9-1), 0.91 (95% CI, 0.86-0.96), and 0.98 (95% CI, 0.86-1), respectively. Napsin A expression was not associated with survival or clinicopathologic factors. In the group of cases without diagnostic consensus for CCC, 50% showed ≥1+ napsin A expression; all napsin A-negative cases had previously been classified as non-CCC by ≥2 reviewers, whereas only 37.5% of the napsin A-positive cases had been classified as CCC by 2 of the 3 reviewers. In conclusion, napsin A is a sensitive and specific biomarker of the clear cell histotype in endometrial carcinomas and accordingly may have diagnostic utility in their histotyping.
高分级子宫内膜癌伴透明细胞的组织学分型可能存在显著的观察者间变异性，这表明一种能够区分子宫内膜透明细胞癌（CCC）与其模拟物的生物标志物将具有诊断效用。本研究基于 9 家机构诊断为 CCC 的 77 例病例，评估了 napsin A 免疫组化在 CCC 诊断中的作用。在由 3 位病理学家组成的亚组中进行独立审查后，所有 3 位审查者均达成诊断共识的病例（n=60）被用于建立“共识组”，作为与主要贡献者一致的金标准，以评估 napsin A 的性能。从共识组的 54 例具有必要材料的病例中以及从 49 例子宫内膜子宫内膜样癌（所有分级）和 17 例子宫内膜浆液性癌中构建了 1.0mm 厚的组织微阵列。对微阵列和 17 例没有诊断共识的病例进行 napsin A 免疫组化分析，评分基于免疫反应细胞的比例（0、1+、2+和 3+分别表示 0%、1%至 25%、26%至 49%和≥50%的免疫反应细胞）。49 例可评估核心的 CCC 病例的评分分布如下：0，n=6；1+，n=6；2+，n=8；3+，n=29。在可评估病例中，CCC 中≥1+ napsin A 免疫反应的频率明显高于子宫内膜浆液性癌（1/13，7.7%；P<0.0001）和子宫内膜子宫内膜样癌（0/49，0%；P<0.0001）。≥1+ napsin A 表达预测共识性透明细胞表型的敏感性、特异性、阴性预测值和阳性预测值分别为 0.88（95%置信区间 [CI]，0.75-0.95）、0.98（95% CI，0.9-1）、0.91（95% CI，0.86-0.96）和 0.98（95% CI，0.86-1）。napsin A 表达与生存或临床病理因素无关。在没有 CCC 诊断共识的病例组中，有 50%表现出≥1+ napsin A 表达；所有 napsin A 阴性病例此前均被≥2 位审查者分类为非 CCC，而在 3 位审查者中的 2 位分类为 CCC 的病例中，只有 37.5%为 napsin A 阳性。综上所述，napsin A 是子宫内膜癌透明细胞组织学分型的敏感和特异性生物标志物，因此在其组织学分型中可能具有诊断效用。
