Clinicopathological implications of expressions of hypoxia-related molecules in esophageal superficial squamous cell carcinoma

Ogane, Naoki; Yasuda, Masanori; Shimizu, Michio; Miyazawa, Masaki; Kamoshida, Shingo; Ueda, Akiko; Takata, Ken; Sakuma, Yuji; Miyagi, Yohei; Kameda, Yoichi

doi:10.1016/j.anndiagpath.2009.10.003

« Previous Next »Annals of Diagnostic Pathology
Volume 14, Issue 1 , Pages 23-29, February 2010

Clinicopathological implications of expressions of hypoxia-related molecules in esophageal superficial squamous cell carcinoma

Naoki Ogane, PhD
- Division of Pathology, Kanagawa Cancer Center Hospital, Kanagawa 241-0815, Japan
Masanori Yasuda, MD, PhD
- Department of Pathology, Saitama Medical University International Medical Center, Saitama 350-1298, Japan
- Correspondence author. Tel.: +81 42 984 0609; fax: +81 42 984 0609.
Michio Shimizu, MD, PhD
- Department of Pathology, Saitama Medical University International Medical Center, Saitama 350-1298, Japan
Masaki Miyazawa, PhD
- Department of Pathology, Tokai University School of Medicine, Kanagawa 259-1193, Japan
Shingo Kamoshida, PhD
- Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan
Akiko Ueda, MD, PhD
- Division of Pathology, Kanagawa Cancer Center Hospital, Kanagawa 241-0815, Japan
Ken Takata, MD, PhD
- Division of Surgery, Kanagawa Cancer Center Hospital, Kanagawa 241-0815, Japan
Yuji Sakuma, MD, PhD
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa 241-0815, Japan
Yohei Miyagi, MD, PhD
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa 241-0815, Japan
Yoichi Kameda, MD, PhD
- Division of Pathology, Kanagawa Cancer Center Hospital, Kanagawa 241-0815, Japan

Abstract

This study was conducted to clarify whether or not expressions of hypoxia-related molecules would have clinicopathological significance in squamous cell carcinoma (SCC) of the esophagus. Expressions of hypoxia inducible factor-1 alpha (HIF-1α), glucose transporter 1 (GLUT-1) and RAC-1 were immunohistochemically analyzed in 96 surgically resected SCCs at pT1b (sm1, 12 cases; sm2, 35 cases; sm3, 49 cases). They were divided into a lymph node metastasis (LNM)–positive group composed of 44 cases and an LNM-negative group composed of 52 cases. Immunohistochemical profiles were estimated based on the staining extent (score: 1+, 2+, 3+) and intensity (score: 1+, 2+, 3+). A significant expression pattern was found in the nucleus for HIF-1α, cell membrane for GLUT-1 and cytoplasm for RAC-1. The cases were categorized into a high score group (total score of 4 or more) and a low score group (total score of 3 or less) in each maker, respectively. A comparison made between the LNM-positive group and the LNM-negative group showed that the proportion of cases with a high score was larger in the LNM-positive group than in the LNM-negative group (HIF-1α, P = .02; GLUT-1, P = .008; RAC-1, P = .001). Among them, HIF-1α was found to be significantly related to the disease-free survival (P = .019) and overall survival (P = .034) as well as LNM (disease-free survival, P = .030; overall survival, P = .030). The multivariate analysis demonstrated that the HIF-1α expression would be an independent indicator for prognosis. In the superficial SCCs of the esophagus, GLUT-1 and RAC-1 may be involved in LNM, and HIF-1α overexpression is expected to predict an unfavorable clinical outcome.