Novel Immunohistochemical Profiling of Small-Cell Lung Cancer: Correlations Between Tumor Subtypes and Immune Microenvironment.

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).

METHODS

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.

RESULTS

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).

CONCLUSIONS

This study highlights the need to integrate the novel SCLC classification with data regarding the TIME to better inform patient prognosis and treatment.