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


METHODS
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.
Soltermann
Alex
A
Institute for Surgical Pathology, Department of Pathology, University Hospital Zürich, Zürich, Switzerland. alex.soltermann@usz.ch
Tischler
Verena
V
Arbogast
Stefanie
S
Braun
Julia
J
Probst-Hensch
Nicole
N
Weder
Walter
W
Moch
Holger
H
Kristiansen
Glen
G
D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology; D003094:Collagen / Q000096:biosynthesis; D004549:Elastin / Q000096:biosynthesis; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D012737:Sex Factors; D046888:Tissue Array Analysis; D053675:Versicans / Q000096:biosynthesis; D014746:Vimentin / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D014746:Vimentin; D053675:Versicans; D003094:Collagen; D004549:Elastin