Histopathological features of HER2 overexpression in uterine carcinosarcoma: proposal for requirements in HER2 testing for targeted therapy

Histopathological features of HER2 overexpression in uterine carcinosarcoma: proposal for requirements in HER2 testing for targeted therapy
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子宫癌肉瘤中HER2过度表达的组织病理学特征:靶向治疗HER2检测要求的建议

DOI:
10.1007/s00428-021-03017-5
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发表时间:
2021
期刊:
影响因子:
3.5
通讯作者:
Yonemori Kan
Yonemori Kan
中科院分区:
医学3区
文献类型:
--
作者:
Yoshida Hiroshi;Nishikawa Tadaaki;Matsumoto Koji;Mori Masahiko;Hirashima Yasuyuki;Takehara Kazuhiro;Ariyoshi Kazuya;Hasegawa Kosei;Yonemori Kan

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子宫癌肉瘤是一种少见且高度侵袭性的肿瘤。尽管开发了HER 2抗体偶联物,但没有UCS的HER 2检测方案。我们的目的是阐明UCS中的组织病理学HER 2表达细节,比较胃癌和乳腺癌的ASCO/CAP标准之间的HER 2评分,并提出UCS的HER 2检测要求。从2018年5月至2020年7月前瞻性收集了84例转移性/复发性UCS患者的89份标本。我们对89例标本进行了HER 2免疫组化(IHC),对44例标本进行了FISH。根据胃癌(2016)和乳腺癌(2018)的最新ASCO/CAP标准评价HER 2表达详情和HER 2评分。在89份标本中,根据胃癌标准,HER 2 IHC评分为0的有31例(35%),1+的有26例(29%),2+的有22例(25%),3+的有10例(11%)。在HER 2评分为2+/3+的28/32(88%)份标本中观察到外侧/基底外侧膜染色模式。在28/32(88%)份HER 2评分为2+/3+的标本中确定了HER 2瘤内异质性。胃和乳腺标准之间HER 2评分的总体一致率为70%。FISH结果显示,10/44例(23%)标本中HER 2基因扩增,仅表现为侧/基底外侧膜染色模式。基于UCS中HER 2表达的组织病理学特征,应应用可接受外侧/基底外侧染色模式的评分系统。此外,我们提出了UCS检测的具体要求,包括标本选择、评分系统和计算HER 2阳性细胞比例。
Uterine carcinosarcoma (UCS) is an uncommon and highly aggressive tumor. There is no HER2 testing protocol for UCS despite the development of HER2 antibody conjugates. We aimed to elucidate histopathological HER2 expression details in UCS, to compare HER2 scores between ASCO/CAP criteria for gastric and breast cancer, and to propose requirements for HER2 testing for UCS. Eighty-nine specimens from 84 patients with metastatic/recurrent UCS were prospectively collected from May 2018 to July 2020. We performed HER2 immunohistochemistry (IHC) for 89 specimens and FISH for 44 specimens. HER2 expression details and HER2 score were evaluated according to the latest ASCO/CAP criteria for gastric (2016) and breast cancer (2018). HER2 IHC scores according to the gastric cancer criteria were 0 in 31 cases (35%), 1+ in 26 (29%), 2+ in 22 (25%), and 3+ in 10 cases (11%) of the 89 specimens. A lateral/basolateral membranous staining pattern was observed in 28/32 (88%) specimens with HER2 scores of 2+/3+. HER2 intratumoral heterogeneity was identified in 28/32 (88%) of the specimens with HER2 scores of 2+/3+. The overall concordance rate of HER2 score was 70% between the gastric and breast criteria. FISH revealedHER2gene amplification in 10/44 (23%) specimens containing only lateral/basolateral membranous staining pattern. Based on the histopathological features of HER2 expression in UCS, a scoring system that accepts lateral/basolateral staining patterns should be applied. Furthermore, we proposed specific requirements for UCS testing, including specimen selection, scoring system, and calculating the proportion of HER2-positive cells.
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