Background: The prevalence of locally advanced esophageal squamous cell carcinoma (ESCC) remains high despite technological advancements in its diagnosis. This leads to prolonged multimodality treatment often resulting in poor response eventually leading to poor prognosis. Currently, there are no biomarkers available to predict response to neoadjuvant chemotherpy. Aldehyde dehydrogenase 1 (ALDH1), human epidermal growth factor receptor-2 (HER2), p16INK4A, ploidy and S phase fraction are considered significant biomarkers in various solid malignancies. However, there is paucity of data on their clinical significance in ESCC. In the present study, we investigated their significance in predicting the response to neoadjuvant chemotherapy (NACT) in ESCC patients.

Methods: Immunohistochemisty of ALDH1, HER2, p16INK4A and propidium iodide based cell cycle analysis through flow cytometer was performed in pre treatment biopsy sample collected from 108 ESCC patients who were presented at a comprehensive cancer centre in northeast India and all of them subsequently received neo adjuvant chemotherapy. Results: ALDH 1, HER2 and p16INK4A were found positive in 65.7%, 7.4% and 22% of pre treatment ESCC specimens respectively. ALDH1 expression correlates with poor response to neo adjuvant chemotherapy (P<0.001). A significant proportion of poor responders were found to be smokers (P=0.004). Poor responders also tends to correlate with increased mortality (P=0.009). HER2 couldn’t predict response to NACT. However, all HER2 positive cases were associated with high ALDH1 expression (P=0.034). 50% of those with pathologically complete response were p16 positive on the contrary only 15% non responders were positive for p16 (P<0.001). 84% of the ESCC patients reported aneuploid tumor status and responder's were found having high S phase fraction (P=0.041). Conclusion: High ALDH1 expression can predict poor response whereas high p16 and S phase fraction can indicate good response to neoadjuvant chemotherapy in ESCC patients. HER2 seems having no clinical significance in the response assessment of neo adjuvant chemotherapy in ESCC.

Citation Format: Rajeev Kumar, R. Ravi Kannan, Akalesh Kumar Verma, Anuradha Talukdar, Monoj Kumar Deka, Ritesh Tapkire, Litika Vermani, Sankar Kumar Ghosh. High ALDH1, S phase fraction, p16INK4A in esophageal squamous cell carcinoma could predict response to neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2788. doi:10.1158/1538-7445.AM2017-2788

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.