关键词: PAX1 PAX8 Thymic carcinoma Thymoma Thymus

Mesh : Animals Humans Mice Biomarkers, Tumor / metabolism Carcinoma, Neuroendocrine / diagnosis metabolism Neoplasms, Glandular and Epithelial / diagnosis Thymoma / pathology Thymus Neoplasms / pathology

来  源:   DOI:10.1016/j.humpath.2023.09.007

Abstract:
Thymic epithelial neoplasms are morphologically diverse and can pose a diagnostic challenge that is complicated by a lack of immunohistochemistry (IHC) markers that are entirely sensitive and specific for thymic epithelium. Polyclonal PAX8 is often used in this context, but it is not a specific marker. The PAX1 transcription factor shares significant homology with PAX8 and plays an integral role in thymic development in humans and murine models. This study evaluated the role of PAX1 IHC in differentiating thymic epithelial neoplasms from morphologic mimics on whole slide tissue sections. The PAX1 antibody stained all 74 thymoma cases; however, there was wide variability in staining intensity within each subtype. The antibody was less sensitive in thymic carcinomas and thymic neuroendocrine tumors compared to thymomas and demonstrated weak staining in a subset of morphologic mimics (21 squamous cell carcinomas, 6 pulmonary neuroendocrine tumors, 1 mesothelioma, 1 lymphoblastic lymphoma, and 1 granulosa cell tumor). With a H-score positive threshold of 75, the antibody had 100% specificity, and sensitivities of 92%, 56%, and 47% in thymomas, thymic neuroendocrine tumors, and thymic carcinomas respectively. The PAX1 antibody showed frequent geographic reduction in staining consistent with compromised antigenicity from variable formalin fixation. PAX1 IHC has a moderate-to-high sensitivity for thymic epithelial neoplasms; however, the wide staining variability and fixation effects may lead to difficulty with consistent interpretation. This marker is unlikely to supplant the role of PAX8 in diagnostic practice, but it may be a useful addition to immunohistochemistry panels when evaluating for thymic primary tumors.
摘要:
胸腺上皮肿瘤在形态上是多种多样的,并且可以提出诊断挑战,由于缺乏对胸腺上皮完全敏感和特异性的免疫组织化学(IHC)标记而使其复杂化。多克隆PAX8经常在这种情况下使用,但它不是一个特定的标记。PAX1转录因子与PAX8具有显著同源性,并且在人和鼠模型的胸腺发育中起着不可或缺的作用。这项研究评估了PAX1IHC在区分整个载玻片组织切片上的胸腺上皮肿瘤与形态模拟物中的作用。PAX1抗体对所有74例胸腺瘤进行了染色;然而,每个亚型的染色强度差异很大.与胸腺瘤相比,该抗体在胸腺癌和胸腺神经内分泌肿瘤中的敏感性较低,并且在形态学模拟物的子集中表现出较弱的染色(21个鳞状细胞癌,6肺神经内分泌肿瘤,1间皮瘤,1淋巴母细胞淋巴瘤,和1个颗粒细胞瘤)。在H评分阳性阈值为75的情况下,抗体具有100%的特异性,和92%的敏感度,56%,和47%的胸腺瘤,胸腺神经内分泌肿瘤,和胸腺癌。PAX1抗体在染色中显示出频繁的地理减少,这与来自可变福尔马林固定的受损抗原性一致。PAX1IHC对胸腺上皮肿瘤具有中等至高度的敏感性;然而,广泛的染色变异性和固定效应可能导致难以一致的解释。该标记不太可能取代PAX8在诊断实践中的作用,但在评估胸腺原发性肿瘤时,它可能是免疫组织化学面板的有用补充。
公众号