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Originally published as JHC exPRESS on August 17, 2009.
doi:10.1369/jhc.2009.954263
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Journal of Histochemistry and Cytochemistry
Volume 57 (12): 1183-1193, 2009
Copyright © 2009 Author et al.

Application of a Novel Method of Double APAAP Staining With Subsequent Quantitative Image Analysis to the Examination of Integrin Expression in Undifferentiated-type Gastric Carcinomas

Natalia Yanchenko, Hiroyuki Sugihara and Takanori Hattori

Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan

Correspondence to: Natalia Yanchenko, Department of Pathology, Shiga University of Medical Science, Seta-Tsukinowa cho, Otsu-shi, 520-2192, Japan. E-mail: natalia.yanchenko{at}gmail.com

In undifferentiated-type gastric carcinoma (UGC), recognition of cancer cells is not easy, which has hampered its precise phenotypic analysis. To examine alterations of the integrin phenotype during the progression of UGC, we used double alkaline phosphatase anti-alkaline phosphatase staining and computer-aided image analyses for the expression of {alpha}1, {alpha}2, {alpha}3, {alpha}5, {alpha}6, {alpha}V, β1, and β4 integrin subunits and {alpha}Vβ3, {alpha}Vβ5, and {alpha}Vβ6 integrins in cytokeratin-positive cells in the mucosal, the submucosal, and the deeper parts of 10 early and 17 advanced UGCs, their non-neoplastic counterparts, and 9 lymph node (LN) metastases. We revealed declining expression of epithelial integrin subunits ({alpha}2, {alpha}3, {alpha}6, β4) and increasing expression of mesenchymal integrin subunits ({alpha}1, {alpha}5) as the tumor invaded deeper, reflecting gradual epithelial-to-mesenchymal transition of the integrin phenotype during tumor invasion. Enhanced expression of the {alpha}V integrin subunit and {alpha}Vβ3 and {alpha}Vβ5 integrins correlated with tumor invasion, and that of {alpha}Vβ6 integrins with LN metastasis. Our results have demonstrated that the method we introduced is suitable for analysis of dynamic alterations of the integrin repertoire in UGC progression. (J Histochem Cytochem 57:1183–1193, 2009)

Key Words: integrin • gastric carcinoma • EMT • double staining • image analysis


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