Clinicopathological and genomic features of superficial esophageal squamous cell carcinomas in nondrinker, nonsmoker females

• Published in: Cancer medicine (Malden, MA) Vol. 13; no. 4; pp. e7078 - n/a
• Main Authors: Fukuhara, Motomitsu, Urabe, Yuji, Nakahara, Hikaru, Ishikawa, Akira, Ishibashi, Kazuki, Konishi, Hirona, Mizuno, Junichi, Tanaka, Hidenori, Tsuboi, Akiyoshi, Yamashita, Ken, Hiyama, Yuichi, Takigawa, Hidehiko, Kotachi, Takahiro, Yuge, Ryo, Hayes, C. Nelson, Oka, Shiro
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.02.2024; Wiley
• Subjects: Alcohol; Dehydrogenases; Deoxyribonucleic acid; Dissection; DNA; Endoscopy; Esophageal cancer; Esophageal carcinoma; esophageal neoplasms; esophageal squamous cell carcinoma; Esophagitis; Esophagus; Females; Genetic analysis; Genetic testing; Genomics; Immunohistochemistry; Keratinization; Lesions; Males; Medical prognosis; Multivariate analysis; Mutation; nondrinker; nonsmoker females; reflux esophagitis; Regression analysis; Risk factors; Smoking; Squamous cell carcinoma; Thorax; United States > US; Japan; esophageal squamous cell carcinoma; genomics; reflux esophagitis; nondrinker; esophageal neoplasms; nonsmoker females
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.7078

Background Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non‐drinker and non‐smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. Methods The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry. Results Multiple logistic regression revealed that older age, fewer multiple Lugol‐voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid‐thoracic esophagus, posterior wall side, with 0‐IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. Conclusion Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0‐IIa ESCC with keratinization of the posterior wall of the mid‐thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment. Our study revealed that older non‐drinker, non‐smoker females with RE and fewer multiple LVLs might develop longitudinal 0‐IIa ESCC with keratinization of the posterior wall of the mid‐thoracic esophagus. These lesions had a low frequency of KMT2D alterations and a high frequency of CDKN2A alterations, with less KMT2D‐positive and more p16‐positive immunostaining.