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

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.

• Authors: Kotaro Hirashima, Ken-Ichi Iyama, Yoshifumi Baba, Yumi Honda, Yoshikazu Sado, Yoshifumi Ninomiya, Masayuki Watanabe, Hiroshi Takamori, Toru Beppu, Hideo Baba
• Journal: Journal of surgical oncology (J Surg Oncol) Vol. 107 Issue 4 Pg. 402-7 (Mar 2013) ISSN: 1096-9098 [Electronic] United States
• PMID: 22927259 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Biomarkers, Tumor
• COL4A2 protein, human
• COL4A6 protein, human
• Collagen Type IV
• Ki-67 Antigen
• Tumor Suppressor Protein p53

Topics

• Aged
• Analysis of Variance
• Basement Membrane (chemistry, pathology)
• Bile Duct Neoplasms (chemistry, pathology)
• Bile Ducts, Extrahepatic (chemistry, pathology)
• Biomarkers, Tumor (analysis)
• Carcinoma (chemistry, pathology)
• Collagen Type IV (analysis)
• Down-Regulation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Ki-67 Antigen (analysis)
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Predictive Value of Tests
• Prognosis
• Proportional Hazards Models
• Tumor Suppressor Protein p53 (analysis)