Expression of smooth muscle calponin in tumor vessels of human hepatocellular carcinoma and its possible association with prognosis

Authors

  • Yo Sasaki M.D., Ph.D.,

    Corresponding author
    1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
    • Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka City 537-8511, Japan
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    • Fax: 81-6-6981-8055

  • Hisako Yamamura Ph.D.,

    1. Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Yuriko Kawakami M.D., Ph.D.,

    1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Terumasa Yamada M.D., Ph.D.,

    1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Masahiro Hiratsuka M.D., Ph.D.,

    1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Masao Kameyama M.D., Ph.D.,

    1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Hiroaki Ohigashi M.D., Ph.D.,

    1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Osamu Ishikawa M.D., Ph.D.,

    1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Shingi Imaoka M.D., Ph.D.,

    1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Shingo Ishiguro M.D., Ph.D.,

    1. Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
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  • Katsuhito Takahashi M.D., Ph.D.

    1. Department of Molecular Medicine and Pathophysiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka City, Japan
    2. Solution-Oriented-Research for Science and Technology (SORST), Japan Science and Technology Corporation, Higashinari-ku, Osaka City, Japan
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Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a vascular-rich tumor. The tumor vessels in HCC were demonstrated to have α-smooth muscle actin positive smooth muscle cells (SMCs). However, it is unclear whether the SMCs in the wall of the tumor vessels are differentiated or undifferentiated. Basic calponin is an actin-, tropomyosin-, and calmodulin-binding protein, and expression of the calponin gene in SMCs has been recognized as one of the late stage differentiation markers of SMCs. The authors investigated the differentiation state of SMCs in tumor vessels by immunohistochemical examination of calponin in patients with HCC, and whether it is associated with the patients' prognosis.

METHODS

Tumor and nontumor tissues were obtained from 75 patients with HCC who underwent radical hepatic resection. The differentiation state of the smooth muscle cells were evaluated based on the expression level of calponin, an actin-binding protein, using immunohistochemistry and reverse transcription–polymerase chain reaction analysis. The disease free survival (DFS) rates were estimated according to the Kaplan–Meier method comparing groups of patients with calponin positive and negative tumor vessels. A multivariate analysis based on the Cox proportional hazards regression model was performed to estimate whether the expression of calponin is an independent prognostic factor.

RESULTS

In the 75 patients with HCC examined, 36 patients (48%) possessed calponin positive SMCs, and the remaining 39 (52%) did not. There were no significant differences in either clinical or pathologic factors between the two groups of patients. The 5- and 8-year DFS rate of the patients with calponin positive vessels were 37% and 26%, respectively. These values were significantly higher (11% and 5%) than those of patients with calponin negative vessels. Gender, TNM classification, perioperative transfusion, and calponin expression were found to be independent prognostic factors for DFS.

CONCLUSIONS

Immunohistochemical examination of the calponin expression in the tumor vessels is a new and useful means to predict the prognosis of HCC patients after hepatic resection. Cancer 2002;94:1777–86. © 2002 American Cancer Society.

DOI 10.1002/cncr.10402

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