SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract.
SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract.
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DOI：
10.1097/pas.0000000000000285
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发表时间：
2014-09
期刊：
影响因子：
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通讯作者：
Westra WH
中科院分区：
文献类型：
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作者：
Bishop JA;Antonescu CR;Westra WH
SMARCB 1（INI-1）是位于染色体22q11.2上的肿瘤抑制基因。其基因产物在所有正常组织的细胞核中普遍表达。SMARCB 1基因失活与一组不同的恶性肿瘤的发病机制有关，这些恶性肿瘤倾向于共享“横纹肌样”细胞形态学。这组SMARCB 1缺陷型肿瘤现在被鼻窦道中出现的一组癌进一步扩大。对142例鼻窦癌进行SMARCB 1免疫组化染色。通过荧光原位杂交（FISH）进一步表征显示表达缺失的肿瘤的SMARCB 1缺失。免疫组化显示，142例原发性鼻窦癌中有9例（6%）SMARCB 1表达缺失。5例患者为女性，患者年龄范围为33-78岁（平均59岁）。SMARCB 1缺陷型肿瘤的特征为细胞巢、细胞片和细胞索，没有任何特异性（例如鳞状或腺性）分化的组织学证据。肿瘤由不同比例的基底样细胞和横纹肌样细胞组成。SMARCB 1缺陷型癌被诊断为非角化鳞状细胞癌（n=3）、鼻窦未分化癌（n=2）、肌上皮癌（n =2）、非肠腺癌（n=1）和未另行说明的癌（n=1）。FISH分析显示SMARCB 1缺失6 8（75%）癌。SMARCB 1缺陷型癌没有携带人乳头瘤病毒或NUT-1变异。6例患者表现为T4疾病，5例患者发生局部复发和/或远处转移，4例死于疾病。SMARCB 1肿瘤抑制基因的失活似乎参与了鼻窦癌的发病机制，进一步扩大了SMARCB 1缺陷型肿瘤的家族，并进一步描述了一组令人困惑的低分化/未分化的侵袭性肿瘤。通过免疫组化检测SMARCB 1丢失的能力，特别是在处理具有基底细胞样或横纹肌样特征的低分化癌时，应有助于更全面地了解这些鼻窦癌，包括临床行为和对靶向治疗的反应。
SMARCB1 (INI-1) is a tumor suppressor gene located on chromosome 22q11.2. Its gene product is ubiquitously expressed in nuclei of all normal tissues. SMARCB1 gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share “rhabdoid” cytomorphology. This group of SMARCB1-deficient tumors is now further expanded by a subset of carcinomas arising in the sinonasal tract. SMARCB1 immunostaining was performed on 142 sinonasal carcinomas. Tumors that showed loss of expression were further characterized for SMARCB1 deletions by fluorescence in situ hybridization (FISH). Nine of 142 (6%) primary sinonasal carcinomas showed loss of SMARCB1 expression by immunohistochemistry. Five patients were women, and patients ranged in age from 33–78 years (mean 59). The SMARCB1 deficient tumors were characterized by nests, sheets, and cords of cells without any histologic evidence of specific (e.g. squamous or glandular) differentiation. The tumors were comprised of varying proportions of basaloid and rhabdoid cells. The SMARCB1 deficient carcinomas had been diagnosed as non-keratinizing squamous cell carcinomas (n=3), sinonasal undifferentiated carcinomas (n=2), myoepithelial carcinoma (n=2), non-intestinal adenocarcinoma (n=1) and carcinoma, not otherwise specified (n=1). FISH analysis revealed SMARCB1 deletions in 6 of 8 (75%) carcinomas. The SMARCB1 deficient carcinomas did not harbor human papillomavirus or NUT-1 alterations. Six patients presented with T4 disease, 5 patients developed local recurrences and/or distant metastases, and four died of their disease. Inactivation of the SMARCB1 tumor suppressor gene appears to be involved in the pathogenesis of a subset of sinonasal carcinomas, further expanding the family of SMARCB1 deficient neoplasms and further delineating a bewildering group of poorly/undifferentiated, aggressive carcinomas arising at this site. The ability to detect SMARCB1 loss by immunohistochemistry, particularly when dealing with poorly differentiated carcinomas with basaloid or rhabdoid features, should facilitate a more comprehensive understanding of these sinonasal carcinomas including clinical behavior and response to targeted therapies.