Wu Di, Hiroshima Kenzo, Yusa Toshikazu, Ozaki Daisuke, Koh Eitetsu, Sekine Yasuo, Matsumoto Shinji, Nabeshima Kazuki, Sato Ayuko, Tsujimura Tohru, Yamakawa Hisami, Tada Yuji, Shimada Hideaki, Tagawa Masatoshi
Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Owada-Shinden 477-96, Yachiyo, Chiba 276-8524, Japan.
Department of General Thoracic Surgery and Asbestos Disease Center, Chiba Rosai Hospital, Tatsumidai-higashi 2-16, Ichihara 290-0003, Japan.
Ann Diagn Pathol. 2017 Feb;26:31-37. doi: 10.1016/j.anndiagpath.2016.10.010. Epub 2016 Oct 22.
Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.
恶性间皮瘤是一种侵袭性很强的肿瘤，组织学亚型是最可靠的预后因素之一。一些双相性间皮瘤很难与具有非典型纤维性间质的上皮样间皮瘤区分开来。本研究的目的是通过荧光原位杂交（FISH）和BAP1免疫组化分析间皮瘤中p16/CDKN2A缺失情况，以评估其在双相性间皮瘤诊断中的潜在作用。我们收集了38例胸膜间皮瘤病例。本研究结果清楚地将29例双相性间皮瘤与9例上皮样间皮瘤区分开来。双相性间皮瘤中p16/CDKN2A纯合缺失的比例总体为96.6%（28/29）。在19例双相性间皮瘤中有18例（94.7%）观察到p16/CDKN2A纯合缺失，且每例上皮样和肉瘤样成分之间p16/CDKN2A缺失状态的一致性为100%。在9例上皮样间皮瘤中有7例（77.8%）观察到p16/CDKN2A纯合缺失，但在纤维性间质中未观察到。在13例双相性间皮瘤中有5例（38.5%）观察到BAP1缺失，且在上皮样和肉瘤样成分中均有。在8例上皮样间皮瘤中有5例（62.5%）观察到BAP1缺失，但在纤维性间质中未观察到。p16/CDKN2A纯合缺失在双相性间皮瘤中很常见，仅分析间皮瘤的一个成分就足以表明肿瘤是恶性的。然而，与单纯组织学相比，对梭形间皮细胞进行p16/CDKN2A状态的FISH分析和BAP1免疫组化提供了一种更客观的方法来区分双相性间皮瘤和具有非典型基质细胞的上皮样间皮瘤。
