2023 World Conference on Lung Cancer (Posters)-P2.13. Molecular Subtyping of Small Cell Lung Carcinoma: An Attempt at Unravelling Its Biological Heterogeneity

P2.13. Molecular Subtyping of Small Cell Lung Carcinoma: An Attempt at Unravelling Its Biological Heterogeneity - PDF(Abstract)

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This presentation explores the molecular subtyping of Small Cell Lung Carcinoma (SCLC) in an effort to understand its biological heterogeneity. The study included 907 histologically confirmed cases of SCLC over an 8-year period. Immunohistochemical analyses for four novel transcription regulators (ASCL1, NEUROD1, YAP1, POU2F3) and Rb1 were performed on 178 selected cases. The majority of patients were elderly males with a positive smoking history. Over 90% of the tumors were centrally located and 83% showed metastatic disease. <br /> <br />The initial diagnostic panel showed expression of synaptophysin, chromogranin, CD56, INSM1, pancytokeratin, TTF1, and loss of Rb1. The molecular sub-classification based on the expression of the four transcription regulators revealed that the SCLC-A and SCLC-N subtypes encompassed the majority of cases, while SCLC-Y, SCLC-P, and quadruple negative subtypes constituted smaller proportions. A quarter of cases were dual positive. Classic/Neuroendocrine (NE) high SCLC cases were predominantly of the SCLC-A/N/AN subtype, while NE low cases were mostly of the SCLC-Y/P subtypes. <br /><br />The study found significant correlations between certain subtypes and supraclavicular lymphadenopathy on follow-up. Survival analysis using Kaplan-Meier curve showed relatively poorer outcomes for SCLC-Y/P subtypes. The researchers concluded that while there were no appreciable morphological differences, SCLC showed heterogeneity at the level of neuroendocrine differentiation, transcriptional regulation, and biological behavior. <br /><br />This research provides important insights into the molecular characteristics and potential subtypes of SCLC, which could have implications for understanding the disease's heterogeneity and developing tailored treatments.

Asset Subtitle

Arkadipta Mukherjee

Meta Tag

Speaker Arkadipta Mukherjee

Topic SCLC & Neuroendocrine Tumors: Biomarkers & Radiomics

Keywords

molecular subtyping

Small Cell Lung Carcinoma

SCLC

biological heterogeneity

transcription regulators

Rb1

centrally located tumors

metastatic disease

neuroendocrine differentiation

tailored treatments