Differential expression of basement membrane type IV collagen α2 and α6 chains as a prognostic factor in patients with extrahepatic bile duct carcinoma

Authors

  • Kotaro Hirashima MD, PhD,

    1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
    2. Department of Surgical Pathology, Kumamoto University Hospital, Kumamoto City, Kumamoto, Japan
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  • Ken-Ichi Iyama MD, PhD,

    Corresponding author
    1. Department of Surgical Pathology, Kumamoto University Hospital, Kumamoto City, Kumamoto, Japan
    • Department of Surgical Pathology, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan. Fax: +81-96-373-7099.===

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  • Yoshifumi Baba MD, PhD,

    1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
    2. Department of Surgical Pathology, Kumamoto University Hospital, Kumamoto City, Kumamoto, Japan
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  • Yumi Honda MD, PhD,

    1. Department of Surgical Pathology, Kumamoto University Hospital, Kumamoto City, Kumamoto, Japan
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  • Yoshikazu Sado PhD,

    1. Division of Immunology, Shigei Medical Research Institute, Okayama City, Okayama, Japan
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  • Yoshifumi Ninomiya MD, PhD,

    1. Department of Molecular Biology and Biochemistry, Graduate School of Medical Sciences, Okayama University, Okayama City, Okayama, Japan
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  • Masayuki Watanabe MD, PhD, FACS,

    1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
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  • Hiroshi Takamori MD, PhD, FACS,

    1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
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  • Toru Beppu MD, PhD, FACS,

    1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
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  • Hideo Baba MD, PhD, FACS

    1. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan
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  • The content is solely the responsibility of the authors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No conflicts of interest exist.

Abstract

Background

The destruction of the basement membrane (BM) is the first step in cancer invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct α(IV) chains; α1(IV) to α6(IV). The loss of α5(IV) and α6(IV) chains from the epithelial BM at the early stage of cancer invasion has been reported in several types of cancers. However, the expression of α5(IV) and α6(IV) chains in extrahepatic bile duct carcinoma (EBDC) remains unclear.

Methods

We examined the expression of α(IV) chains by immunohistochemistry using 71 resected EBDC specimens. Prognostic significance of α(IV) chains was examined by Cox regression and Kaplan–Meier analyses.

Results

In the invasive cancer, the expression of α6(IV) chain in the BM was lost partially or completely preceded by the loss of α2(IV) chain. The loss of α6(IV) chain in the BM of the invasive cancer was related to the tumor classification, TNM stages, and the expression of α2(IV) chain. The patients with α2(IV)-negative and α6(IV)-negative chains had significantly poorer prognosis than those with α2(IV)-positive and α6(IV)-positive/negative chains (P = 0.04).

Conclusions

The loss of α2(IV) and α6(IV) chains might be a useful prognostic factor in patients with EBDC. J. Surg. Oncol. 2013;107:402–407. © 2012 Wiley Periodicals, Inc.

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