Watanabe Yukio, Shiraishi Kouya, Takahashi Fumiaki, Yoshida Akihiko, Suzuki Kenji, Asamura Hisao, Takeuchi Masahiro, Furuta Koh, Tsuta Koji
Division of Pathology, National Cancer Centre Hospital, Tokyo, Japan.
Department of Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
Histopathology. 2015 Jun;66(7):939-48. doi: 10.1111/his.12556. Epub 2015 Feb 5.
Pulmonary adenosquamous carcinoma (ASC) is more aggressive than adenocarcinoma (AC) and squamous cell carcinoma (SCC). The genetic features and biomarkers of ASC are not well known. Here, we attempted to identify potential therapeutic markers for ASC.
Surgically resected ASC samples from 65 patients were analysed. We examined the expression of β III-tubulin, thymidylate synthase, breast cancer susceptibility gene 1 and ribonucleotide reductase M1 (RRM1); identified mutations in epidermal growth factor receptor (EGFR), KRAS, BRAF and HER2; and detected ALK, ROS1 and RET rearrangements. Gene amplification and expression of EGFR, human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor-1 and MET were also examined. β III-Tubulin showed the highest expression (P = 0.002), and its expression was more frequent in the AC than in the SCC component (P = 0.013). RRM1 expression was more frequent in the SCC component (P = 0.046). EGFR and KRAS mutations were detected in both components (21.5 and 10.9%, respectively). ALK and ROS1 rearrangements and MET amplification were detected in both components in one (1.5%) case.
In ASC, drug response-specific gene alterations could occur in both AC and SCC components, suggesting that patients with confirmed or suspected ASC should undergo further testing for driver gene analyses.
肺腺鳞癌（ASC）比腺癌（AC）和鳞状细胞癌（SCC）侵袭性更强。ASC的基因特征和生物标志物尚不明确。在此，我们试图确定ASC的潜在治疗标志物。
分析了65例患者手术切除的ASC样本。我们检测了βⅢ-微管蛋白、胸苷酸合成酶、乳腺癌易感基因1和核糖核苷酸还原酶M1（RRM1）的表达；鉴定了表皮生长因子受体（EGFR）、KRAS、BRAF和HER2的突变；并检测了ALK、ROS1和RET重排。还检测了EGFR、人表皮生长因子受体2（HER2）、成纤维细胞生长因子受体-1和MET的基因扩增及表达。βⅢ-微管蛋白表达最高（P = 0.002），且其在AC成分中的表达比在SCC成分中更常见（P = 0.013）。RRM1表达在SCC成分中更常见（P = 0.046）。在两种成分中均检测到EGFR和KRAS突变（分别为21.5%和10.9%）。在1例（1.5%）患者的两种成分中均检测到ALK和ROS1重排以及MET扩增。
在ASC中，AC和SCC成分均可能发生药物反应特异性基因改变，这表明确诊或疑似ASC的患者应接受进一步检测以进行驱动基因分析。
