PAX2 Distinguishes Benign Mesonephric and Mullerian Glandular Lesions of the Cervix From Endocervical Adenocarcinoma, Including Minimal Deviation Adenocarcinoma
PAX2 Distinguishes Benign Mesonephric and Mullerian Glandular Lesions of the Cervix From Endocervical Adenocarcinoma, Including Minimal Deviation Adenocarcinoma
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DOI：
10.1097/pas.0b013e3181c89c98
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发表时间：
2010-02-01
影响因子：
5.6
通讯作者：
Zaloudek, Charles J.
中科院分区：
文献类型：
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作者：
Rabban, Joseph T.;McAlhany, Stephanie;Zaloudek, Charles J.
子宫颈中肾残余是胚胎中肾系统的残余，通常在女性发育过程中退化。不常见的是中肾残余增生。旺盛中肾增生的鉴别诊断包括宫颈小偏差腺癌，这是一种形态平淡的肿瘤，目前尚无可靠的诊断生物标志物。PAX2编码一种转录因子，在Wolffian导管系统的发展中是必需的。该蛋白在几种中肾源性肿瘤中表达，包括肾细胞癌、肾母细胞瘤和肾源性腺瘤。我们假设PAX2也可能在子宫颈中肾病变中表达，并可能区分子宫颈中肾增生和小偏差腺癌。我们证实PAX2在中肾残体（6 / 6）和中肾增生（18 / 18）中强烈和弥漫性表达，但在中肾腺癌中未发现表达（0 / 1）。PAX2在正常宫颈腺（包括管状簇和Nabothian囊肿）（86 / 86）、小叶宫颈腺增生（5 / 5）、输卵管/输卵管子宫内膜样化生（8 / 8）和宫颈子宫内膜异位症（14 / 14）中表达。而宫颈内腺癌中PAX2阳性仅2例[最小偏离型浸润性腺癌（5例中0例），普通型浸润性腺癌（22例中1例），子宫内膜样腺癌（1例）]。邻近原位腺癌和纯原位腺癌（6例中0例）也呈PAX2阴性。PAX2在2例宫颈内膜阳性腺癌中的表达呈斑片状、弱表达。大多数（15例中的11例）II期子宫内膜样腺癌缺乏PAX2表达，但10例I级肿瘤中有1例和5例2级肿瘤中有3例表达PAX2。这些结果提示PAX2免疫反应性可能有助于(1)区分中肾增生与小偏差腺癌，(2)区分宫颈小叶腺增生与小偏差腺癌，(3)区分宫颈输卵管化生或宫颈子宫内膜异位症与宫颈原位腺癌。总体而言，宫颈腺增生中强烈的弥漫性PAX2核表达模式预示良性诊断（阳性预测值90%，阴性预测值98%，P < 0.001）；然而，PAX2不应脱离病变的结构和细胞学特征来解释，因为它可能在一些II期子宫内膜腺癌中表达，包括子宫颈。
Mesonephric remnants of the cervix are vestiges of the embryonic mesonephric system which typically regresses during female development. Uncommonly, hyperplasia of the mesonephric remnants may occur. The differential diagnosis of exuberant mesonephric hyperplasia includes minimal deviation adenocarcinoma of the cervix, a tumor with deceptively bland morphology for which no reliable diagnostic biomarkers currently exist. PAX2 encodes a transcription factor necessary in the development of the Wolffian duct system.. and the protein is expressed in several tumors of mesonephric origin, including renal cell carcinoma, Wilm tumor, and nephrogenic adenoma. We hypothesized that PAX2 may also be expressed in mesonephric lesions of the cervix and may distinguish mesonephric hyperplasia from minimal deviation adenocarcinoma of the cervix. We demonstrated that PAX2 was strongly and diffusely expressed in mesonephric remnants (6 of 6) and in mesonephric hyperplasia (18 of 18),however, no expression was noted in mesonephric adenocarcinoma (0 of 1). PAX2 was expressed in normal endocervical glands (including tunnel clusters and Nabothian cysts) (86 of 86), lobular endocervical glandular hyperplasia (5 of 5), tubal/tuboendometrioid metaplasia (8 of 8), and cervical endometriosis (13 of 14). In contrast, only 2 cases of endocervical adenocarcinoma were positive for PAX2 [invasive adenocarcinoma of the minimal deviation type (0 of 5), usual type (I of 22), and endometrioid type (1 of 1)]. Adjacent adenocarcinoma in Situ, as well as cases of pure adenocarcinoma in situ (0 of 6), were also PAX2 negative. PAX2 expression in the 2 positive endocervical adenocarcinomas was patchy and weak. Most (11 of 15) stage II endometrial endometrioid adenocarcinomas lacked PAX2 expression but I of 10 grade I tumors and 3 of 5 grade 2 tumors did express PAX2. These results suggest that PAX2 immunoreactivity may be useful to (1) distinguish mesonephric hyperplasia from minimal deviation adenocarcinoma, (2) to distinguish lobular endocervical glandular hyperplasia from minimal deviation adenocarcinoma, and (3) to distinguish endocervical tubal metaplasia or cervical endometriosis from endocervical adenocarcinoma in situ. Overall, a strong, diffuse nuclear PAX2 expression pattern in a cervical glandular proliferation predicts a benign diagnosis (positive predictive value 90%, negative predictive value 98%; P < 0.001); however, PAX2 should not be interpreted in isolation from the architectural and cytologic features of the lesion as it may be expressed in some stage II endometrial adenocarcinomas involving the cervix.