A Comprehensive Analysis of PAX8 Expression in Human Epithelial Tumors
A Comprehensive Analysis of PAX8 Expression in Human Epithelial Tumors
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DOI：
10.1097/pas.0b013e318216c112
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发表时间：
2011-06-01
影响因子：
5.6
通讯作者：
Hirsch, Michelle S.
中科院分区：
文献类型：
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作者：
Laury, Anna R.;Perets, Ruth;Hirsch, Michelle S.
PAX 8是在甲状腺、苗勒管和肾/上尿路的胚胎发生中重要的配对盒基因，并且PAX 8的表达先前已在来自这些部位中的每一个的癌中描述。然而，尚未进行包括来自甲状腺、肾脏或苗勒管系统以外的多个器官部位的各种上皮肿瘤的大型研究。本研究的目的是基于对广泛的上皮肿瘤的评价来评价PAX 8免疫染色的效用。对来自多个器官的1357个肿瘤（486个肿瘤在全组织切片中，871个肿瘤在组织微阵列中，主要是上皮）进行PAX 8免疫组织化学。仅核染色评分为阳性，并评价肿瘤的染色程度和强度。还对多种肿瘤细胞系进行了PAX 8的蛋白质印迹分析。核PAX 8染色存在于91%（60/66）甲状腺肿瘤，90%（158/176）肾细胞癌（RCC），81%（13/16）肾嗜酸细胞瘤，99%（164/165）高级别卵巢浆液性癌，71%非浆液性卵巢上皮性肿瘤32/49例，宫颈上皮病变91%（10/11），子宫内膜腺癌98%（152/155）。在其余719例评价的肿瘤中，只有30例（4%），包括12例胸腺肿瘤，3例膀胱尿路上皮癌，4例肺鳞状细胞癌，2例食管腺癌，1例胰腺癌，2例胆管癌，1例卵巢支持-间质细胞瘤，1例卵巢性索间质瘤，3例睾丸混合生殖细胞瘤和1例腺泡细胞癌，显示至少弱或局灶性PAX 8阳性。出乎意料的发现是在胸腺瘤和胸腺癌的子集中PAX 8的弥漫性、中度染色。剩余的689个肿瘤，包括但不限于来自前列腺、结肠、胃、肝、肾上腺和头颈部的肿瘤，以及来自肺、子宫颈和卵巢的小细胞癌，是PAX 8阴性的。PAX 8特异性通过蛋白质印迹分析证实，因为仅在卵巢和RCC细胞系中检测到表达。这些结果表明PAX 8是甲状腺、肾、苗勒管和胸腺肿瘤的高度敏感的标志物。重要的是，所有肺腺癌、乳腺和肾上腺肿瘤以及大多数胃肠道肿瘤对PAX 8均呈阴性。因此，PAX 8是确定原发肿瘤部位的极好标志物。在一个病例子集中，可能需要其他标志物，包括但不限于甲状腺转录因子-1，RCC和Wilms肿瘤-1，以区分3种最常见的PAX 8阳性肿瘤。
PAX8 is a paired-box gene important in embryogenesis of the thyroid, Mullerian, and renal/upper urinary tracts, and expression of PAX8 has been previously described in carcinomas from each of these sites. However, a large study including a wide variety of epithelial neoplasms from multiple organ sites other than the thyroid, kidney, or Mullerian system has not been performed. The goal of this study was to evaluate the utility of PAX8 immunostaining based on the evaluation of a wide range of epithelial tumors. PAX8 immunohistochemistry was performed on 1357 tumors (486 tumors in whole-tissue sections and 871 tumors in tissue microarrays, predominantly epithelial) from multiple organs. Only nuclear staining was scored as positive, and tumors were evaluated for the extent and intensity of staining. Western blot analysis with PAX8 was also performed on multiple tumor cell lines. Nuclear PAX8 staining was present in 91% (60 of 66) of thyroid tumors, 90% (158 of 176) of renal cell carcinomas (RCCs), 81% (13 of 16) of renal oncocytomas, 99% (164 of 165) of high-grade ovarian serous carcinomas, 71% (32 of 49) of nonserous ovarian epithelial neoplasms, 91% (10 of 11) of cervical epithelial lesions, and 98% (152 of 155) of endometrial adenocarcinomas. Of the remaining 719 evaluated tumors, only 30 cases (4%), including 12 thymic neoplasms, 3 bladder urothelial carcinomas, 4 lung squamous cell carcinomas, 2 esophageal adenocarcinomas, 1 pancreatic adenocarcinoma, 2 cholangiocarcinomas, 1 ovarian Sertoli-Leydig cell tumor, 1 ovarian sex cord stromal tumor, 3 testicular mixed germ cell tumors, and 1 acinic cell carcinoma, showed at least weak or focal PAX8 positivity. The unexpected finding was diffuse, moderate staining of PAX8 in a subset of thymomas and thymic carcinomas. The 689 remaining tumors, including but not limited to those from the prostate, colon, stomach, liver, adrenal gland, and head and neck, and small cell carcinomas from the lung, cervix, and ovary, were PAX8 negative. PAX8 specificity was confirmed by Western blot analysis, as expression was detected only in ovarian and RCC cell lines. These results show that PAX8 is a highly sensitive marker for thyroid, renal, Mullerian, and thymic tumors. Importantly, all lung adenocarcinomas, breast and adrenal neoplasms, and the majority of gastrointestinal tumors were negative for PAX8. Therefore, PAX8 is an excellent marker for confirming primary tumor site. In a subset of cases, additional markers, including but not limited to thyroid transcription factor-1, RCC, and Wilms tumor-1, may be needed to distinguish between the 3 most common PAX8-positive tumors.