NEUROENDOCRINE MARKERS AS A PROGNOSTIC TOOL IN SMALL CELL LUNG CARCINOMA UNDERGOING CHEMOTHERAPY

Introduction: Small cell lung carcinoma (SCLC) has recently been classified into four molecular subtypes, according to differential key transcription regulators expression. Among these, ASCL1 and NEUROD1 double negative subtypes, in addition to POU2F3 or YAP1 positive subtypes, are characterized by having either low or absent neuroendocrine (NE) markers on immunohistochemical expression. Research focusing on novel SCLC subtypes is useful to improve care in SCLC, particularly through the evaluation of molecular surrogates currently being used in clinical practice, such as NE markers. Objective: We evaluated the prognostic role of NE immunohistochemical expression in SCLC patients who underwent chemotherapy. Methods: This single-center retrospective analysis included patients with a diagnosis of SCLC from 2007 to 2020, for whom at least two immunohistochemical NE markers were performed and evaluated by an institutional pathologist. Patients were required to receive at least two cycles of chemotherapy. Patients were classified as having either Low or non-Low NE status, with a low status being defined if at least two NE markers were negative or weak in expression. Kaplan Meier curves and log-rank test were used to evaluate overall survival (OS) and progression-free survival (PFS) among subgroups. Results: Eighty-three patients were included for the final analysis. Synaptophysin, chromogranin, and CD56 were tested in 99%, 97%, and 49% of patients, respectively. Nine patients were classified as having a Low NE status. Baseline characteristics among subgroups disclosed no statistically significant difference regarding extensive-stage status or CNS metastatic status, even though none of the patients with a Low-NE had CNS metastasis. On survival analysis, a Low NE status was associated with a significantly better OS (HR 0.5, p=0.03 – log-rank test) when compared to a non-Low NE status. There was no statistically significant difference in PFS (p=0.1). Conclusion: This study demonstrates that NE immunohistochemical expression is prognostic in SCLC undergoing chemotherapy. Our group is further evaluating the correlation between NE markers, SCLC molecular subtypes, and immunologic features.