Background: Early diagnosis and early treatment are the best ways to improve cancer patient prognoses and keep quality of life of the patients after treatment. We developed ELPS (endoscopic laryngo-pharyngeal surgery) as an endoscopic treatment for superficial pharyngeal carcinoma. ELPS was performed on 278 patients of superficial carcinoma of the pharynx. However 18 lesions have lymphatic invasion, and lymphatic metastasis have occurred in 10 patients after ELPS. HOXB9, a member of the HOX genes, has been reported to be overexpressed in some neoplastic tissues. The class I HOXB gene family consists of 39 members with a shared and highly conserved 61-amino acid homeodomain motif. These genes are significant regulators of development, and their roles in neoplastic transformation and tumor progression have been recognized. Some studies have suggested that HOXB9 expression promotes cellular invasiveness, metastatic ability, and tumor vascularization in the surrounding tissue by inducing EMT. These findings imply that HoxB9 overexpression may alter tumor-specific cell fates and the tumor stromal microenvironment, contributing to lymphatic invasion of superficial carcinoma. The objective of this study is to analyze whether HOXB9 expression associates with lymphatic invasion and causes in lymph node metastasis of superficial pharyngeal carcinoma. METHODS: A total of 36 superficial pharyngeal carcinoma patients who underwent endoscopic surgery were examined. Immunohistochemical staining was performed to evaluate the expression of HoxB9, and the association of lymphatic invasion and lymph node metastasis with HoxB9 expression was analyzed. RESULTS: Of the 36 superficial pharyngeal carcinoma specimens, depth of tumor invasion is epithelial layer (EP) in 19 tumors and submucosal layer (SEP) in 17 tumors. Thirteen of 19 (68.4%) EP tumors showed HoxB9 expression, and 10 of 17 (58.8%) SEP tumor showed HOXB9 expression. There is no significant correlation of HOXB9 expression and depth of tumor invasion. Six of the 36 tumors have lymphatic invasion. All tumors having lymphatic invasion showed positive HoxB9 expression, whereas 17 of 30 having no lymphatic invasion showed HoxB9 expression. HoxB9 positive tumors tend to have lymphatic invasion (p=0.07). Five of the 36 patients have lymphatic metastasis. Four of 5 patients (80%) who have lymph node metastasis showed positive HoxB9 expression, whereas 19 of 31 (61.3%) who have no lymph node metastasis showed HoxB9 expression. HOXB9 positive tumors tend to have lymphatic invasion. Conclusions: Our results suggest that HOXB9 can play a significant role in lymphatic invasion of superficial pharyngeal carcinoma and can be a novel molecular maker for the lymphatic metastasis.

Citation Format: Hirofumi Kawakubo, Mai Tsutsui, Rieko Nakamura, Tsunehiro Takahashi, Norihito Wada, Yoshiro Saikawa, Tai Omori, Hiroya Takeuchi, Yuko Kitagawa. HOXB9 expression associate with lymphatic invasion in superficial pharyngeal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 50. doi:10.1158/1538-7445.AM2014-50