Abstract 4658: Clinical characteristics, molecular subtypes, and prognosis of 176 surgically resected esophageal small cell carcinoma patients
Authors: Ruijie Ma, Peng Wu, Chaoqi Zhang, Nan Sun, Jie He
Journal: Cancer Research (2025)

Introduction: Small cell carcinoma of the esophagus (SCCE) is an aggressive neuroendocrine gastrointestinal malignancy with poor prognosis, and accounts for 0.8%-2.4% of all histological types of esophageal malignant tumors worldwide. The pathological characteristics of SCCE are similar to those of small cell lung cancer (SCLC), and SCLC subtypes can be defined by differential expression of four key transcription regulators: ASCL1, NeuroD1, YAP1 and POU2F3. However, there is limited research on the molecular subtypes of SCCE. Here, we conducted the study to classify the molecular subtype of SCCE, and explored the relationship between SCCE molecular subtypes and patients' clinical pathological characteristics and prognosis. Methods: Patients with surgically resected SCCE at the Cancer Hospital of the Chinese Academy of Medical Sciences between 1985 and 2019 were included in the study. Clinicopathologic data of SCCE patients were collected, including gender, age, alcohol abuse, tobacco abuse, BMI, family history, location of tumor, length of tumor, TNM stage, lymphovascular invasion, and treatment. Immunohistochemical staining was performed to calculate the H-scores of ASCL1, NeuroD1, YAP1, and POU2F3 of FFPE sample. Data processing and analyses were performed using SPSS 27, R (4.4.1), and the R package survival [3.7.0]. Results: A total of 176 patients were included in the study. The median overall survival (OS) for all SCCE patients included in the study was 21 months, and the median disease-free survival (DFS) for all SCCE patients included in the study was 13 months. Four subtypes of SCCE samples were categorized by H-score: high ASCL1 (SCCE-A), high NeuroD1 (SCCE-N), high YAP1 (SCCE-Y) and high POU2F3 (SCCE-P). Univariate Cox analysis indicated that the SCCE-P subtype, adjuvant therapy, T stage, TNM stage, lymphovascular invasion, tumor length, T stage, and TNM stage were significantly associated with patient DFS (p &amp;lt; 0.05), while adjuvant therapy, T stage, TNM stage, lymphovascular invasion, tumor length, T stage, and TNM staging were significantly associated with patient OS (p &amp;lt; 0.05). Multivariate COX analysis indicated that adjuvant therapy, tumor length, and the SCCE-P subtype were independent significant predictors of patient DFS (p &amp;lt; 0.05), while adjuvant therapy and tumor length were independent significant predictors of patient OS (p &amp;lt; 0.05). The subtypes of SCCE had no significant relationship with clinicopathologic factors of patients. Conclusion: This study indicate that the SCCE-P subtype is an independent prognostic factor for DFS in SCCE patients, providing a reference for the molecular classification of SCCE and helping to more accurately identify the disease status and prognosis of SCCE patients. Additionally, the study observed that adjuvant therapy after surgery for SCCE patients can significantly improve both OS and DFS. Citation Format: Ruijie Ma, Peng Wu, Chaoqi Zhang, Nan Sun, Jie He. Clinical characteristics, molecular subtypes, and prognosis of 176 surgically resected esophageal small cell carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4658.