Notch Intracellular Domain (NICD) Expression and Clinical Manifestations of Second Primary Tumor at Esophagus in Patients with Head and Neck Squamous Cell Carcinoma

Tauangtham Anekpuritanang; Warut Pongsapich; Tanasarun Watcharadilokkul; Premyot Ngaotepprutaram; Paveena Pithuksurachai; Sacarin Bunbanjerdsuk

doi:10.2147/OTT.S227745

Notch Intracellular Domain (NICD) Expression and Clinical Manifestations of Second Primary Tumor at Esophagus in Patients with Head and Neck Squamous Cell Carcinoma

Onco Targets Ther. 2019 Dec 17:12:11175-11181. doi: 10.2147/OTT.S227745. eCollection 2019.

Authors

Tauangtham Anekpuritanang¹, Warut Pongsapich², Tanasarun Watcharadilokkul², Premyot Ngaotepprutaram², Paveena Pithuksurachai², Sacarin Bunbanjerdsuk³

Affiliations

¹ Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
² Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
³ Section for Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Abstract

Introduction: Second primary tumor (SPT) is a major factor that affects the survival of head and neck squamous cell carcinoma (HNSCC) patients, and the esophagus is a common site. Detection of SPT is essential for optimal HNSCC treatment planning and follow-up. Mutation of the NOTCH1 gene is common in head and neck cancer. However, details relating to Notch signaling and clinical outcomes among different primary tumors are still inconclusive. This study aimed to identify the role of the Notch signaling pathway in HNSCC, and to compare NOTCH1 expression in HNSCC compared between those with and without SPT at esophagus while focusing on the Notch intracellular domain (NICD).

Methods: Twenty-three cases of esophageal SPT and 47 non-SPT controls that were treated at Siriraj Hospital during 2006-2017 were included. Patient information and clinical outcomes were analyzed. NICD expression demonstrated by immunohistochemistry technique in formalin-fixed paraffin-embedded specimens was studied.

Results: Mean age of SPT and non-SPT was 55.13 and 62.09 years, respectively, and 94.3% of patients were male. Regarding SPT detection, 82.6% were synchronous and 17.4% were metachronous. There was significantly more active smoking among SPT than among non-SPT (87.0% vs 51.1%, p=0.01). Active alcohol use was also significantly greater among SPT than among non-SPT (87.0% vs 61.7%; p=0.04). Hypopharynx was the most common primary tumor site among SPT. Three-year and 5-year survival among SPT patients was 38.0% and 25.3%, respectively. NICD expression was absent in 52.2% of SPT, and in 53.3% of non-SPT. NICD expression intensity was mostly weak or moderate.

Conclusion: Active smoking and alcohol use were found to be significantly associated with SPT development. A high percentage of NICD inactivation was noted in HNSCC with no significant difference between groups. The Notch signaling pathway is involved in HNSCC tumorigenesis, but may not be a suitable molecular marker for SPT development.

Keywords: NOTCH; esophagus; head and neck cancer; second primary tumor; synchronous cancer.