目的:Cowden综合征(CS)是一种多系统疾病,其一生内患恶性肿瘤的风险较高。我们旨在评估PTEN免疫染色在各种常见CS相关肿瘤中作为CS筛查测试的作用。特别关注皮肤肿瘤。
方法:我们回顾性搜索了2008年至2022年符合CS标准和/或证明种系PTEN突变的患者。然后,我们对这些患者的肿瘤以及对照病例进行了PTEN免疫染色。
结果:我们的研究包括30例CS患者,这些患者总共有25例CS相关恶性肿瘤(13例甲状腺,8乳房,和4个子宫内膜癌)。具体来说,有11例活检证实的CS相关皮肤肿瘤,包括1例多发性毛癣瘤和3例多发性硬化性纤维瘤。总的来说,45个CS相关肿瘤(6个毛癣瘤,7个硬化性纤维瘤,5甲状腺癌,18个腺瘤状甲状腺结节,6乳腺癌,和3例子宫内膜癌)和31例非CS病例(9例三膜瘤,5硬化性纤维瘤,8个腺瘤状甲状腺结节,3甲状腺,3乳房,和3个子宫内膜癌)可用于PTEN免疫组织化学染色。PTEN表达在45个CS相关病变的43个(96%)中丢失,在31个散发性肿瘤的30个(97%)中保留。PTEN表达缺失作为CS筛选试验的总体敏感性和特异性分别为96%和97%,分别。
结论:PTEN免疫组化对CS相关肿瘤,尤其是三色膜,可以作为一个容易获得和具有成本效益的CS筛选测试。
OBJECTIVE: Cowden syndrome (CS) is a multisystem disease with an elevated lifetime risk of internal malignancy. We aim to assess the role of PTEN immunostain as a screening test for CS in a variety of common CS-associated neoplasms, with a particular focus on cutaneous tumors.
METHODS: We retrospectively searched for patients meeting criteria for CS and/or demonstrating germline PTEN mutation from 2008 to 2022. We then performed PTEN immunostains on tumors of these patients as well as control cases.
RESULTS: Our study included 30 patients with CS who had a total of 25 CS-associated malignancies (13 thyroid, 8 breast, and 4 endometrial carcinomas). Specifically, there were 11 patients with biopsy-confirmed CS-associated cutaneous neoplasms, including 1 patient with multiple trichilemmomas and 3 with multiple sclerotic fibromas. In total, 45 CS-associated tumors (6 trichilemmomas, 7 sclerotic fibromas, 5 thyroid carcinomas, 18 adenomatous thyroid nodules, 6 breast carcinomas, and 3 endometrial carcinomas) and 31 non-CS cases (9 trichilemmomas, 5 sclerotic fibromas, 8 adenomatous thyroid nodules, and 3 thyroid, 3 breast, and 3 endometrial carcinomas) were available for PTEN immunohistochemical staining. PTEN expression was lost in 43 (96%) of 45 CS-associated lesions and retained in 30 (97%) of 31 sporadic tumors. The overall sensitivity and specificity of PTEN loss of expression as a screening test for CS were 96% and 97%, respectively.
CONCLUSIONS: PTEN immunohistochemistry on CS-associated tumors, especially trichilemmomas, can serve as a readily accessible and cost-effective screening test for CS.