Down-regulation of artery in moderately differentiated hepatocellular carcinoma related to tumor development

Fujita, Nobuhiro; Aishima, Shinichi; Iguchi, Tomohiro; Nishihara, Yunosuke; Yamamoto, Hidetaka; Taketomi, Akinobu; Oda, Yoshinao; Honda, Hiroshi; Tsuneyoshi, Masazumi

doi:10.1016/j.humpath.2009.11.011

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Volume 41, Issue 6 , Pages 838-847, June 2010

Down-regulation of artery in moderately differentiated hepatocellular carcinoma related to tumor development

Nobuhiro Fujita, MD
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Shinichi Aishima, MD, PhD
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Corresponding author.
Tomohiro Iguchi, MD, PhD
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Yunosuke Nishihara, MD, PhD
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Hidetaka Yamamoto, MD, PhD
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Akinobu Taketomi, MD, PhD
- Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Yoshinao Oda, MD, PhD
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Hiroshi Honda, MD, PhD
- Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Masazumi Tsuneyoshi, MD, PhD
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

Received 3 August 2009; received in revised form 9 November 2009; accepted 12 November 2009. published online 26 February 2010.

Summary

Hepatocellular carcinoma develops in a multistep process. Previous studies have revealed changes in blood supply in hepatocellular carcinoma during its carcinogenesis. However, little is known about the relationship between tumor vasculature and the biological behavior of moderately differentiated hepatocellular carcinoma which demonstrates varied degrees of biological behavior. We immunohistochemically assessed intratumoral arterial vessel density (by high-molecular-weight caldesmon and calponin) and microvessel density (by CD34) in 123 cases of moderately differentiated hepatocellular carcinomas, and compared these densities with clinicopathological findings. Arterial vessel density and microvessel density of 19 well-differentiated and 37 poorly differentiated hepatocellular carcinomas were also evaluated. The arterial vessel density of moderately differentiated hepatocellular carcinomas with capsule formation, infiltration to the capsule, portal venous invasion, and high Ki-67 labeling index was lower than that of moderately differentiated hepatocellular carcinomas without these pathological findings (high-molecular-weight caldesmon: P < .0001, P = .0074, P = .0009, P = .0244, calponin: P < .0001, P = .0695, P = .0033, and P = .0155, respectively). The low arterial vessel density group (<10) of moderately differentiated hepatocellular carcinomas tended to show poorer overall survival than the high arterial vessel density group (≥10) (high-molecular-weight caldesmon: P = .0347, calponin: P = .0404). The arterial vessel density and microvessel density of moderately differentiated hepatocellular carcinomas were significantly higher than those of well-differentiated hepatocellular carcinomas (high-molecular-weight caldesmon: P = .022, calponin: P = .027, CD34: P = .036) and poorly differentiated hepatocellular carcinomas (high-molecular-weight caldesmon, calponin and CD34: P < .0001). The moderately differentiated hepatocellular carcinomas with lower arterial vessel density had more malignant potential than those with higher arterial vessel density. The changes of arterial vessel density in moderately differentiated hepatocellular carcinomas were suggested.