Vigdorovits Alon, Olteanu Gheorghe-Emilian, Pascalau Andrei-Vasile, Pirlog Radu, Berindan-Neagoe Ioana, Pop Ovidiu-Laurean
Department of Morphological Disciplines, University of Oradea, 410087 Oradea, Romania.
British Columbia Cancer, Department of Pathology, Vancouver, BC V5Z 4E6, Canada.
Diagnostics (Basel). 2024 Nov 26;14(23):2660. doi: 10.3390/diagnostics14232660.
BACKGROUND/OBJECTIVES: Small-cell lung cancer (SCLC) is a highly aggressive malignancy with an emerging molecular classification based on the expression of the transcription factors ASCL1, NEUROD1, and POU2F3. This study aimed to explore the relationship between these novel subtypes and the tumor immune microenvironment (TIME), particularly CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs).
In 51 cases of patients with SCLC, immunohistochemical (IHC) stains for ASCL1, NEUROD1, POU2F3, CD56, Ki67, CD8, and CD4 were performed. H-scores for the novel transcription factors were calculated to determine tumor subtype. CD8+ and CD4+ TIL counts were averaged across 10 high-power fields. The Kruskal-Wallis test and subsequent post hoc Dunn tests were used to determine the differences in transcription factor expression and TILs across subtypes.
In our cohort, 68.62% of our cases were SCLC-A, 9.80% were SCLC-N, 7.84% were SCLC-P, and 13.72% were SCLC-I. Significant differences were observed in the expression of ASCL1, NEUROD1, and POU2F3 across subtypes. CD8+ TILs were more abundant in SCLC-P and SCLC-I. CD8+ TILs were negatively correlated with ASCL1 expression ( < 0.05) and positively correlated with POU2F3 expression ( < 0.005).
This study highlights the need to integrate the novel SCLC classification with data regarding the TIME to better inform patient prognosis and treatment.
背景/目的：小细胞肺癌（SCLC）是一种侵袭性很强的恶性肿瘤，基于转录因子ASCL1、NEUROD1和POU2F3的表达出现了新的分子分类。本研究旨在探讨这些新亚型与肿瘤免疫微环境（TIME）之间的关系，尤其是CD8 +和CD4 +肿瘤浸润淋巴细胞（TILs）。
对51例SCLC患者进行ASCL1、NEUROD1、POU2F3、CD56、Ki67、CD8和CD4的免疫组织化学（IHC）染色。计算新转录因子的H评分以确定肿瘤亚型。在10个高倍视野中平均CD8 +和CD4 + TIL计数。采用Kruskal-Wallis检验及随后的事后Dunn检验来确定各亚型间转录因子表达和TILs的差异。
在我们的队列中，68.62%的病例为SCLC-A，9.80%为SCLC-N，7.84%为SCLC-P，13.72%为SCLC-I。各亚型间ASCL1、NEUROD1和POU2F3的表达存在显著差异。CD8 + TILs在SCLC-P和SCLC-I中更为丰富。CD8 + TILs与ASCL1表达呈负相关（<0.05），与POU2F3表达呈正相关（<0.005）。
本研究强调需要将新的SCLC分类与有关TIME的数据相结合，以更好地为患者的预后和治疗提供信息。
