[Frontiers in Bioscience 14, 3872-3878, January 1, 2009]

The onset of angiogenesis in a multistep process of esophageal squamous cell carcinoma

Yutaro Kubota1, Kazuhiro Kaneko1,2, Kazuo Konishi1, Hiroaki Ito1, Taikan Yamamoto1, Atsushi Katagiri1, Takashi Muramoto1, Yuichiro Yano1, Yoshiya Kobayashi1, Tsunehiro Oyama3, Miki Kushima4, Michio Imawari1

1Department of Gastroenterology, Showa University School of Medicine, Tokyo, 142-8666, Japan,2Division of Digestive Endoscopy/ Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, 277-8577, Japan,3Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan, 4Department of pathology, Showa University School of Medicine, Tokyo, 142-8666, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Patients
3.2. Sample collection
3.3. Histological analysis
3.4. Immunohistochemical Examination
3.5. Evaluation of Immunohistochemical images
3.6. Immunohistochemical quantification
3.7. Statistical Analysis
4. Results
4.1. Characteristics of esophageal precancerous lesions
4.2. Immunohistochemical analysis for CD31, CD105, and VEGFR-2
4.3. MVD of thin and thick vessels for CD31 or CD105
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Microvessel density (MVD) is an excellent predictive biomarker regarding tumor stage and survival in esophageal squamous cell carcinomas (ESCCs). However, it is obscure when tissues initiate angiogenesis in the malignant transformation of human esophageal squamous epithelium. To investigate the onset of angiogenesis in the multistep progressive process of ESCCs, immunohistochemical staining for CD31, CD105, and vascular endothelial growth factor receptor 2 (VEGFR-2) was performed in normal epithelium, Lugol-unstained lesions with non-dysplastic epithelium (LULs-NDE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD) samples. There were significant differences in the mean MVD for CD31 and CD105 between LULs-NDE and LGD (p<0.001, p<0.001), and between LGD and HGD (p<0.001, p=0.006), respectively. Furthermore, a significant difference in MVD for CD105 was seen in normal controls and LULs-NDE (p=0.002), while thick vessels (>10m m) stained with anti-CD105 were not present in normal controls and LULs-NDE despite the presence of these thickened vessels in dysplasia. Our results suggest that CD105 is an efficient marker protein to determine MVD, suggesting that the angiogenic switch occurs at the earliest stage of dysplastic transformation in ESCC.