1. ¹Department of Pathology II, National Defense Medical College, Tokorozawa, Japan
2. ²Department of Surgery I, National Defense Medical College, Tokorozawa, Japan
3. ³Department of Surgery, Self Defense Forces Central Hospital, Tokyo, Japan
4. ⁴Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, Japan
5. ⁵Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
6. ⁶Core Research for Evolutional Science and Technology of the Japan Science and Technology Corporation, Kawaguchi, Japan

Correspondence: Dr H Tsuda, MD, Department of Pathology II, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama 359-8513, Japan. E-mail: htsuda@cc.ndmc.ac.jp

Received 16 April 2004; Revised 25 August 2004; Accepted 9 September 2004; Published online 1 November 2004.

Abstract

The laminin-5 gamma 2 chain (LN-52) is known to be a marker of invasion in several cancer types. Our purpose was to examine the prognostic significance of LN-52 expression in different areas of individual colorectal cancers (CRCs) by using tissue microarrays (TMAs), and to clarify the optimal areas for prognostic assessment. Using formalin-fixed paraffin-embedded tissue blocks of pT3 primary CRCs resected from 120 patients, we constructed TMA blocks of tissue core specimens taken from the submucosal invasive front, subserosal invasive front, central area, and rolled edge of each tumor. Using these four-point TMA sets, cytoplasmic LN-52 expression was immunohistochemically surveyed, and the area-specific prognostic significance of LN-52 expression was evaluated. The data revealed that 35, 30, 15 and 10% of the 120 CRCs showed high-grade LN-52 expression in the submucosal invasive front, subserosal invasive front, central area and rolled edge, respectively. Disease-specific survival curves for the groups with high- and low-grade LN-52 in the submucosal invasive front and subserosal invasive front were different significantly or of marginal difference (respective 5-year survival rates: 54 and 78% for submucosal invasive front (P=0.030) and 58 and 75% for subserosal invasive front (P=0.055)). Multivariate analysis revealed that the grades of LN-52 expression in submucosal invasive front (hazard ratio=2.0, P=0.047) and subserosal invasive front (hazard ratio=2.9, P=0.0033) were independent prognostic factors. In contrast, the grades of LN-52 expression in the central area and rolled edge did not have a significant impact on patient prognosis. Analysis using area-specific four-point TMAs clearly demonstrated that LN-52 expression in the invasive front largely influences the degree of clinical aggressiveness of CRC and its tendency to metastasize.