Kumar Sananda, Singh Navneet, Gupta Parul, Kumar Rajender, Mitra Suvradeep, Bal Amanjit
Department of Histopathology, PGIMER, Chandigarh, India.
Department of Pulmonary and Critical Care Medicine, PGIMER, Chandigarh, India.
APMIS. 2025 Jun;133(6):e70035. doi: 10.1111/apm.70035.
Small cell lung carcinoma (SCLC) was considered a homogenous tumor both morphologically and genetically. Gene expression profiling of SCLC has revealed existence of four distinct subtypes within the SCLC which may impact the prognosis and therapeutic outcome. In the present study, surrogate molecular subtyping of SCLC was done using immunohistochemistry. Histologically confirmed cases of SCLC were included in the study. For molecular sub-typing, primary antibodies specific for ASCL1, POU2F3, NEUROD1, and YAP1 were used. The results were also correlated with baseline demographic and clinical parameters as well as treatment outcome. ASCL1, NEUROD1, and POU2F3 were expressed in 68 (67.3%), 15 (14.9%) and 3 (3.0%) cases, respectively. YAP1 showed cytoplasmic expression in 3 cases (3.0%). ASCL1 and NEUROD1 were co-expressed in 6.9% of cases. The remaining 25.7% of cases were negative for or had low expression of all four transcription factors. SCLC cases were thus classified as ASCL1-dominant, NEUROD1-dominant, ASCL1/NEUROD1 co-expressing, POU2F3-dominant, and Quadruple-negative subtypes. We did not recognize the YAP1 subtype. The overall survival was significantly reduced in the ASCL1 subtype compared to other subtypes. Sub-classification of SCLC patients may help in predicting the prognosis in such patients and may also help in guiding the therapy in the future.
小细胞肺癌（SCLC）在形态学和遗传学上都被认为是一种同质肿瘤。SCLC的基因表达谱分析显示，SCLC内部存在四种不同的亚型，这可能会影响预后和治疗结果。在本研究中，使用免疫组织化学对SCLC进行替代分子亚型分类。组织学确诊的SCLC病例被纳入研究。对于分子亚型分类，使用了针对ASCL1、POU2F3、NEUROD1和YAP1的特异性一抗。结果还与基线人口统计学和临床参数以及治疗结果相关。ASCL1、NEUROD1和POU2F3分别在68例（67.3%）、15例（14.9%）和3例（3.0%）中表达。YAP1在3例（3.0%）中呈细胞质表达。ASCL1和NEUROD1在6.9%的病例中共同表达。其余25.7%的病例对所有四种转录因子均为阴性或低表达。因此，SCLC病例被分类为ASCL1主导型、NEUROD1主导型、ASCL1/NEUROD1共同表达型、POU2F3主导型和四重阴性亚型。我们未识别出YAP1亚型。与其他亚型相比，ASCL1亚型的总生存期显著缩短。SCLC患者的亚分类可能有助于预测此类患者的预后，也可能有助于未来指导治疗。
