Abstract：
DICER1 tumor predisposition syndrome results from pathogenic variants in DICER1 and is associated with a variety of benign and malignant lesions, typically involving kidney, lung, and female reproductive system. Over 70% of sarcomas in DICER1 tumor predisposition syndrome occur in females. Notably, pediatric cystic nephroma (pCN), a classic DICER1 tumor predisposition syndrome lesion, shows estrogen receptor (ER) expression in stromal cells. There are also renal, hepatic, and pancreatic lesions unassociated with DICER1 tumor predisposition syndrome that have an adult female predominance and are characterized/defined by ER-positive stromal cells. Except for pCN, the expression of ER in DICER1-associated lesions remains uninvestigated. In the present study, ER expression was assessed by immunohistochemistry in 89 cases of DICER1-related lesions and 44 lesions lacking DICER1 pathogenic variants. Expression was seen in stromal cells in pCN and pleuropulmonary blastoma (PPB) types I and Ir, whereas anaplastic sarcoma of kidney and PPB types II and III were typically negative, as were other solid tumors of non-Müllerian origin. ER expression was unrelated to the sex or age of the patient. Expression of ER showed an inverse relationship to preferentially expressed antigen in melanoma (PRAME) expression; as lesions progressed from cystic to solid (pCN/anaplastic sarcoma of kidney, and PPB types I to III), ER expression was lost and (PRAME) expression increased. Thus, in DICER1 tumor predisposition syndrome, there is no evidence that non-Müllerian tumors are hormonally driven and antiestrogen therapy is not predicted to be beneficial. Lesions not associated with DICER1 pathogenic variants also showed ER-positive stromal cells, including cystic pulmonary airway malformations, cystic renal dysplasia, and simple renal cysts in adult kidneys. ER expression in stromal cells is not a feature of DICER1 perturbation but rather is related to the presence of cystic components.
摘要：
DICER1肿瘤易感综合征是由DICER1的致病变异引起的，并与多种良性和恶性病变有关，通常涉及肾脏，肺，女性生殖系统DICER1肿瘤易感综合征中超过70%的肉瘤发生在女性中。值得注意的是,小儿囊性肾瘤（pCN），经典的DICER1肿瘤易感性综合征病变，显示基质细胞中的雌激素受体(ER)表达。还有肾脏，肝，和与DICER1肿瘤易感性综合征无关的胰腺病变，以成年女性为主，并以ER阳性基质细胞为特征/定义。除了pCN,ER在DICER1相关病变中的表达仍未被研究.在本研究中,通过免疫组织化学评估了89例DICER1相关病变和44例缺乏DICER1致病变体的病变中的ER表达。在pCN和胸膜肺母细胞瘤（PPB）I型和Ir型的基质细胞中可见表达，而肾脏间变性肉瘤和PPBII型和III型通常是阴性的，其他非穆勒起源的实体瘤也是如此。ER表达与患者的性别或年龄无关。ER的表达与黑色素瘤（PRAME）中优先表达的抗原表达呈负相关；随着病变从囊性发展为实性（肾脏pCN/间变性肉瘤，和PPB类型I至III)，ER表达丢失并且(PRAME)表达增加。因此，在DICER1肿瘤易感性综合征中，没有证据表明非苗勒氏肿瘤是激素驱动的,抗雌激素治疗并非预期有益.与DICER1致病变异无关的病变也显示ER阳性基质细胞，包括囊性肺气道畸形，囊性肾发育不良,和成人肾脏的单纯性肾囊肿。基质细胞中的ER表达不是DICER1扰动的特征，而是与囊性成分的存在有关。
