Differences between low and high grade fetal adenocarcinoma of the lung: a clinicopathological and molecular study
Differences between low and high grade fetal adenocarcinoma of the lung: a clinicopathological and molecular study
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DOI：
10.21037/jtd.2017.07.14
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发表时间：
2017-07-01
影响因子：
2.5
通讯作者：
Liang, Zhi-Yong
中科院分区：
文献类型：
--
作者：
Zhang, Jing;Sun, Jian;Liang, Zhi-Yong
背景：胎儿肺腺癌（FLAC）是一种罕见的肺癌。它分为低级别胎儿腺癌（L-FLAC）和高级别胎儿腺癌（H-FLAC）。我们的目的是报告FLAC在中国patients.Methods的临床病理和分子特征：FLAC筛选从一个连续的肺腺癌系列，包括920例。结果：L-FLAC 3例，H-FLAC 5例。L-FLAC主要发生在年轻患者中，并且在诊断时主要处于I期，并提供了有利的结局。L-FLAC肿瘤的特征是富含糖原的柱状细胞衬在复杂的腺结构上，具有低的核分裂，桑椹胚形成，并且主要是核和细胞质定位的β-连环蛋白表达。相反，H-FLAC主要发生在有吸烟史的老年男性中。H-FLAC的临床分期常较晚期，预后差。H-FLAC肿瘤表现出更突出的细胞核，桑椹胚形成的情况下，主要是膜定位β-连环蛋白。所有5例H-FLAC肿瘤的化学特征均为p53蛋白过表达; L-FLAC肿瘤p53阴性。2例H-FLAC AFP阳性。在所有肿瘤中均未观察到Her-2或ALK-D5 F3过表达。其中1例H-FLAC病例中发现EGFR L 858 R点突变。其中1例L-FLAC患者检测到EGFR T790 M突变。结论：L-FLAC和H-FLAC具有不同的临床病理、免疫表型和分子生物学特征，具有潜在的预后价值。
Background: Fetal adenocarcinoma of the lung (FLAC) is a rare entity of lung cancer. It is classified into low-grade fetal adenocarcinoma (L-FLAC) and high-grade fetal adenocarcinoma (H-FLAC). We aim to report the clinicopathological and molecular features of FLAC in Chinese patients.Methods: FLACs were screened from a consecutive lung adenocarcinoma series comprising 920 cases. The clinicopathological features L-FLAC and H-FLAC were retrospectively reviewed via immunohistochemical study and mutation analysis.Results: Three L-FLAC and five H-FLAC cases were identified. L-FLAC mainly occurred in young patients and was predominantly in stage I upon diagnosis and conferred favorable outcomes. L-FLAC tumors were characterized by the glycogen-rich columnar cells lining the complex glandular structures, with low nuclear atypia, morule formation, and mainly nuclear- and cytoplasmic-localized beta-catenin expression. In contrast, H-FLAC predominantly occurred in elderly men with a history of smoking. The stage of H-FLAC was often advanced at presentation and had a poor prognosis. H-FLAC tumors exhibited more prominent atypia of the nucleus, the absence of morule formation, and largely membrane-localized beta-catenin. All 5 H-FLACs were immunohistochemically characterized by overexpression of the p53 protein; the L-FLAC tumors were negative for p53. Two cases of H-FLAC were positive for AFP. No Her-2 or ALK-D5F3 overexpression was observed in any of the tumors. EGFR L858R point mutation was identified in one of the H-FLAC cases. EGFR T790M mutation was detected in one of the L-FLAC cases. No mutations in KRAS, PIK3CA or BRAF were detected.Conclusions: L-FLAC and H-FLAC exhibited distinctive clinicopathological, immunophenotypic and molecular features with potential prognostic value.