Abstract

Background: Small cell lung carcinoma is a highly aggressive malignancy characterized by poor prognosis and substantial biological heterogeneity. Recent studies have demonstrated that molecular subtyping based on the immunohistochemical expression of transcription factors shows concordance with mRNA expression profiles and has potential applications in clinical practice. Objectives: To evaluate the expression of immunohistochemical markers and molecular subtypes in small cell lung carcinoma, and to analyze the associations between molecular subtypes and selected clinicopathological and immunohistochemical features. Materials and Methods: A cross-sectional descriptive study was conducted on 86 specimens and medical records of patients with small cell lung carcinoma at the National Lung Hospital and Hanoi Oncology Hospital from 2022 to 2025. Immunohistochemical evaluation was performed for CD56, synaptophysin, chromogranin A, TTF-1, Ki-67, and the transcription factors ASCL1, NEUROD1, POU2F3, YAP1, and HNF4A. Positive expression of transcription factors was defined as an H-score >10. Molecular subtypes were determined based on the transcription factor showing the highest H-score and an H-score > 50. Results: Neuroendocrine markers showed high expression in more than 90% of cases. ASCL1 was the most frequently expressed transcription factor (89.5%), followed by NEUROD1 (39.5%). The predominant molecular subtypes were A (73.3%) and N (14%). No significant associations were observed between molecular subtypes and clinicopathological characteristics, TTF-1, or Ki-67 expression. Subtypes A and N were mainly associated with the high neuroendocrine group. Conclusions: Immunohistochemistry may assist in the molecular classification of small cell lung carcinoma on small biopsy specimens in clinical practice. These molecular subtypes reflect the biological heterogeneity of the tumor and warrant further investigation regarding their prognostic significance and potential therapeutic implications.