Somatic mutations and increased lymphangiogenesis observed in a rare case of intramucosal gastric carcinoma with lymph node metastasis.

Naoki Ikari,Shohei Mitani,Akiyoshi Seshimo,Yuji Suehiro,Masakazu Yamamoto,Toru Furukawa,Etsuko Tanji,Tomoko Motohashi,Shota Aoyama,Akiko Serizawa,Takuji Yamada,Kiyoaki Taniguchi,Sawako Yoshina

doi:10.18632/oncotarget.24289

Abstract

Background and aimIntramucosal gastric adenocarcinoma of the well-moderately differentiated type only exhibits lymph node metastasis in extremely rare cases. We encountered such case and investigated both the lymphangiogenic properties and somatic mutations in the cancer to understand the prometastatic features of early-stage gastric cancer.MethodsWe quantitatively measured the density of lymphatic vessels and identified mutations in 412 cancer-associated genes through next-generation target resequencing of DNA extracted from tumor cells in a formalin-fixed and paraffin-embedded tissue. Functional consequence of the identified mutation was examined in vitro by means of gene transfection, immunoblot, and the quantitative real-time polymerase chain reaction assay.ResultsThe intramucosal carcinoma was accompanied by abundant lymphatic vessels. The metastatic tumor harbored somatic mutations in NBN, p.P6S, and PAX8, p.R49H. The PAX8R49H showed significantly higher transactivation activity toward E2F1 than the wild-type PAX8 (P< 0.001).ConclusionsOur data suggest that increased lymphangiogenesis and somatic mutations of NBN and/or PAX8 could facilitate lymph node metastasis from an intramucosal gastric carcinoma. These findings may potentially inform evaluations of the risk of developing lymph node metastasis in patients with intramucosal gastric cancer.

Highlights

An endoscopic resection is recommended as a standard treatment for early gastric carcinomas that fulfill the following criteria: a differentiated-type adenocarcinoma without ulcerative findings, of which the depth of invasion is clinically diagnosed as cT1a and the diameter is ≤ 2 cm [1]
Our data suggest that increased lymphangiogenesis and somatic mutations of NBN and/or paired box 8 (PAX8) could facilitate lymph node metastasis from an intramucosal gastric carcinoma
The lesion seemed to be confined within the gastric mucosa and to fulfill the absolute indication of endoscopic resection, a suspicious lymph node (LN) metastatic lesion (23 mm diameter) beside the left gastric artery was noted on a computed tomography (CT) scan (Figure 1B)

Summary

Introduction

An endoscopic resection is recommended as a standard treatment (absolute indication) for early gastric carcinomas that fulfill the following criteria: a differentiated-type adenocarcinoma without ulcerative findings, of which the depth of invasion is clinically diagnosed as cT1a and the diameter is ≤ 2 cm [1]. This recommendation is based on the rare occurrence of lymph node (LN) metastasis, which is reported to be 0.12% (3/2402) or 0% (0/6456), in patients with early gastric cancer fulfilling the above criteria [1,2,3]. We encountered such case and investigated both the lymphangiogenic properties and somatic mutations in the cancer to understand the prometastatic features of early-stage gastric cancer

Methods

Results

Conclusion