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Prognostic significance of epithelial-mesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer


Soltermann, A; Tischler, V; Arbogast, S; Braun, J; Probst-Hensch, N M; Weder, W; Moch, H; Kristiansen, G (2008). Prognostic significance of epithelial-mesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clinical Cancer Research, 14(22):7430-7437.

Abstract

PURPOSE: In carcinomas, invasive tumor growth is accompanied by desmoplastic stroma reaction and facilitated by epithelial-mesenchymal transition (EMT) of cancer cells. We investigated the prognostic significance of the EMT indicator proteins periostin and vimentin in comparison with versican, a putative indicator of the opposite mechanism mesenchymal-epithelial transition (MET), and to the desmoplasia proteins collagen and elastin in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tumor of 533 patients with surgically resected NSCLC was used for analysis of stromal and epithelial protein expression by immunohistochemistry (EMT-MET proteins) and Elastica van Gieson histochemical staining (collagen and elastin). A semiquantitative sum scoring system was done on three tissue microarrays. RESULTS: Of the 533 patients, 48% had squamous cell carcinoma, 47% adenocarcinoma, and 5% adenosquamous carcinoma. High expression of periostin in either stroma or tumor epithelia, independently scored by two pathologists, correlated with male gender, higher stage, higher pT category, and larger tumor size, and in only stroma with tumor relapse. High expression of versican in either stroma or epithelia as well as of stromal collagen had fewer but concordant associations with advanced tumor and periostin, respectively. High expression of elastin was oppositely associated with less advanced disease. Associations of high vimentin were inconsistent (all P values < 0.05). High stromal periostin was found to be a prognostic factor for decreased progression-free survival on univariate analysis (P = 0.007). CONCLUSIONS: Because up-regulation is frequently observed in the stromal and epithelial tumor compartment, EMT-MET indicator proteins may be integrated in progression models of NSCLC.

PURPOSE: In carcinomas, invasive tumor growth is accompanied by desmoplastic stroma reaction and facilitated by epithelial-mesenchymal transition (EMT) of cancer cells. We investigated the prognostic significance of the EMT indicator proteins periostin and vimentin in comparison with versican, a putative indicator of the opposite mechanism mesenchymal-epithelial transition (MET), and to the desmoplasia proteins collagen and elastin in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tumor of 533 patients with surgically resected NSCLC was used for analysis of stromal and epithelial protein expression by immunohistochemistry (EMT-MET proteins) and Elastica van Gieson histochemical staining (collagen and elastin). A semiquantitative sum scoring system was done on three tissue microarrays. RESULTS: Of the 533 patients, 48% had squamous cell carcinoma, 47% adenocarcinoma, and 5% adenosquamous carcinoma. High expression of periostin in either stroma or tumor epithelia, independently scored by two pathologists, correlated with male gender, higher stage, higher pT category, and larger tumor size, and in only stroma with tumor relapse. High expression of versican in either stroma or epithelia as well as of stromal collagen had fewer but concordant associations with advanced tumor and periostin, respectively. High expression of elastin was oppositely associated with less advanced disease. Associations of high vimentin were inconsistent (all P values < 0.05). High stromal periostin was found to be a prognostic factor for decreased progression-free survival on univariate analysis (P = 0.007). CONCLUSIONS: Because up-regulation is frequently observed in the stromal and epithelial tumor compartment, EMT-MET indicator proteins may be integrated in progression models of NSCLC.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:15 November 2008
Deposited On:10 Dec 2008 08:57
Last Modified:05 Apr 2016 12:39
Publisher:American Association for Cancer Research
ISSN:1078-0432
Publisher DOI:10.1158/1078-0432.CCR-08-0935
PubMed ID:19010860
Permanent URL: http://doi.org/10.5167/uzh-7064

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