Institute for Tissue Diagnostics, MVZ at Helios Klinikum Emil von Behring, 14165 Berlin, Germany.
Department of Pneumology, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany.
Int J Mol Sci. 2023 Jun 23;24(13):10558. doi: 10.3390/ijms241310558.
Pulmonary sarcomatoid carcinoma (PSC) has highly aggressive biological behaviour and poor clinical outcomes, raising expectations for new therapeutic strategies. We characterized 179 PSC by immunohistochemistry, next-generation sequencing and in silico analysis using a deep learning algorithm with respect to clinical, immunological and molecular features. PSC was more common in men, older ages and smokers. Surgery was an independent factor ( < 0.01) of overall survival (OS). PD-L1 expression was detected in 82.1% of all patients. PSC patients displaying altered epitopes due to processing mutations showed another PD-L1-independent immune escape mechanism, which also significantly influenced OS ( < 0.02). The effect was also maintained when only advanced tumour stages were considered ( < 0.01). These patients also showed improved survival with a significant correlation for immunotherapy ( < 0.05) when few or no processing mutations were detected, although this should be interpreted with caution due to the small number of patients studied. Genomic alterations for which there are already approved drugs were present in 35.4% of patients. Met exon 14 skipping was found more frequently (13.7%) and EGFR mutations less frequently (1.7%) than in other NSCLC. In summary, in addition to the divergent genomic landscape of PSC, the specific immunological features of this prognostically poor subtype should be considered in therapy stratification.
肺肉瘤样癌 (PSC) 具有高度侵袭性的生物学行为和较差的临床预后，因此需要新的治疗策略。我们通过免疫组织化学、下一代测序和深度学习算法的计算分析，对 179 例 PSC 进行了临床、免疫和分子特征分析。PSC 更常见于男性、老年和吸烟者。手术是总生存期 (OS) 的独立因素 ( < 0.01)。所有患者中均检测到 PD-L1 表达。显示由于加工突变导致表位改变的 PSC 患者存在另一种 PD-L1 非依赖性免疫逃逸机制，这也显著影响 OS ( < 0.02)。当仅考虑晚期肿瘤时，效果仍然保持 ( < 0.01)。当检测到很少或没有加工突变时，这些患者的免疫治疗也显示出更好的生存获益 ( < 0.05)，尽管由于研究的患者数量较少，应谨慎解释。已有批准药物的基因组改变存在于 35.4%的患者中。外显子 14 跳跃突变更为常见 (13.7%)，而 EGFR 突变较少见 (1.7%)，与其他非小细胞肺癌相比。总之，除了 PSC 不同的基因组图谱外，还应考虑这种预后不良亚型的特定免疫特征，以进行治疗分层。
