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The Expression of Type IV Collagen 6 Chain Is Related to the Prognosis in Patients with Esophageal Squamous Cell Carcinoma

¹ Department of Surgical Pathology, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan
² Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan
³ Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan
⁴ Division of Immunology, Shigei Medical Research Institute, 2117 Yamada, Okayama City, Okayama 701-0202, Japan
⁵ Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medical Sciences, 2-5-1, Shikata-cho, Okayama, Okayama 700-8558, Japan

Correspondence: Address correspondence and reprint requests to: Ken-ichi Iyama, MD, PhD; E-mail: iyama{at}kumamoto-u.ac.jp

Background: The destruction of the basement membrane (BM) is the first step in cancer cell invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct (IV) chains: 1(IV) to 6(IV). The loss of 5/6(IV) chains from the epithelial BM at the early stage of cancer cell invasion has been reported in several cancers. However, the expression of 5/6(IV) chains in esophageal squamous cell carcinoma (ESCC) remains unclear.

Methods: The expression of (IV) chains in 116 resected ESCC specimens was immunohistochemically examined. The role of 6(IV) chain was assessed in ESCC cell lines by short interfering RNA (siRNA).

Results: In intraepithelial carcinoma, the 5/6(IV) chains were stained in a continuous linear pattern in the BM. In some cases of ESCC with the invasion beyond the lamina propria, the 5/6(IV) chains were lost in the BM zone surrounding the cancer cell nests, but in other cases they remained. In the former, the disease-free survival and overall survival were significantly better than in those with the latter. The down-regulation of 6(IV) chain expression by siRNA revealed a slight increase of cancer cell invasiveness.

Conclusions: The evaluation of 5/6(IV) chains may be a useful marker for determining tumor cell properties, as a prognostic factor, in patients with ESCC.

Key Words: Type IV collagen • Basement membrane • Short interfering RNA • Esophageal cancer