title: Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin gamma-2 chain is an early coordinated event in incipient oral squamous cell carcinoma.
abstract: Cancer cell invasion is facilitated by extracellular matrix degrading proteases such as plasmin. We have studied the expression of plasminogen activator inhibitor-1 (PAI-1) and urokinase receptor (uPAR) together with the gamma2-chain of laminin-5 (lam-gamma2) by immunohistochemistry in 20 cases with incipient oral squamous cell carcinoma (SCC). PAI-1-positive neoplastic cells located at the tip of the putative invasive front of grade 1 (incipient) carcinoma were seen in 16 of the 20 cases (75%), whereas adjacent normal and dysplastic epithelium was PAI-1-negative. Clusters of putative invasive neoplastic cells located in the lamina propria were PAI-1-positive in areas with grade 2 incipient carcinoma as were invasive cancer cells in areas of grade 3-4 invasive carcinoma. uPAR immunoreactivity was strongly expressed in numerous stromal cells in the carcinoma area in all 20 lesions, while a few uPAR-positive stromal cells were found in areas with normal and dysplastic epithelium. uPAR-positive neoplastic cell islands located at the front of the lesions were seen in 15 of the 20 cases. The expression pattern of lam-gamma2 was very similar to that of PAI-1; however, lam-gamma2-positive neoplastic cells were only detected in 11 of the 20 cases (55%) in areas of grade 1 incipient carcinoma. Direct comparison of the 3 components revealed colocalization in neoplastic cell islands in both incipient and invasive SCC. Our results suggest that PAI-1 is a novel potential marker of initial invasion in oral SCC, and that the coordinated expression of PAI-1 with uPAR and lam-gamma2 sustain the features of the early invasive cancer cells.
authors.affiliation: Department of Oral Pathology, Center for Oral Health Science, Malmö University, Sweden. Pia.lindberg@od.mah.se
authors.forename: Pia
authors.initials: P
authors.lastname: Lindberg
authors.forename: Ake
authors.initials: A
authors.lastname: Larsson
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007797:Laminin / Q000032:analysis* / Q000276:immunology; D009061:Mouth Mucosa / Q000737:chemistry; D009062:Mouth Neoplasms / Q000737:chemistry*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000276:immunology; D055293:Receptors, Urokinase Plasminogen Activator; D015842:Serine Proteinase Inhibitors / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C400567:LAMC2 protein, human; D007797:Laminin; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D015842:Serine Proteinase Inhibitors