J Cancer 2017; 8(9):1552-1561. doi:10.7150/jca.18685

Research Paper

Vascular Invasion and Stromal S100A4 Expression at the Invasive Front of Colorectal Cancer are Novel Determinants and Tumor Prognostic Markers

Tamotsu Sugai1, Noriyuki Yamada1, Makoto Eizuka1, Ryo Sugimoto1, Noriyuki Uesugi1, Mitsumasa Osakabe1, Kazuyuki Ishida1, Kouki Otsuka2, Akira Sasaki2, Takayuki Matsumoto3✉

1. Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Morioka 020-8505, Japan;
2. Department of Surgery, School of Medicine, Iwate Medical University, 19-1, Morioka 020-8505, Japan;
3. Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1, Morioka 020-8505, Japan.

Abstract

Object: The aim of the present study was to investigate the clinicopathological characteristics and prognostic factors associated with sporadic colorectal cancer (CRC). We examined the clinicopathological findings and immunohistochemical expression of tumor prognostic markers at tumor budding sites to determine their predictive value for patient prognosis.

Materials and Methods: Immunohistochemical examination was performed by tissue microarray (TMA) of specimens from 106 patients with CRC. On hematoxylin and eosin (H&E)-stained tumor tissue slides, a representative area of tumor budding at the invasive front was selected for the construction of a TMA. Immunostaining for matrix metalloproteinase-7 (MMP7), the laminin-5 (ln-5) γ2 chain and S100A4 was performed to determine the association between patient survival and these markers.

Results: Clinicopathological variables were also assessed. Tumor location, histological type, degree of lymphatic invasion and vascular invasion, tumor stage, epithelial expression of S100A4, stromal cell expression of S100A4 and expression of the ln-5γ2 chain were associated with an increased risk of mortality. Five factors were retained in the multivariate logistic regression analysis. Specifically, the tumor location, degree of lymphatic invasion and vascular invasion, tumor stage and stromal cell expression of S100A4 remained significant predictors of patient survival after controlling for the other variables.

Conclusion: Vascular invasion and stromal expression of S100A4 in the tumor budding areas correlated with patient survival. Stromal immunostaining of S100A4 may be useful for identifying high-risk patients with advanced CRC.

Keywords: colorectal cancer, prognostic marker, S100A4, tumor budding, vascular invasion.

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How to cite this article:
Sugai T, Yamada N, Eizuka M, Sugimoto R, Uesugi N, Osakabe M, Ishida K, Otsuka K, Sasaki A, Matsumoto T. Vascular Invasion and Stromal S100A4 Expression at the Invasive Front of Colorectal Cancer are Novel Determinants and Tumor Prognostic Markers. J Cancer 2017; 8(9):1552-1561. doi:10.7150/jca.18685. Available from http://www.jcancer.org/v08p1552.htm