Expression of plasminogen activator inhibitor-1, urokinase receptor and laminin gamma-2 chain is an early coordinated event in incipient oral squamous cell carcinoma.
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.
Lindberg
Pia
P
Department of Oral Pathology, Center for Oral Health Science, Malmö University, Sweden. Pia.lindberg@od.mah.se
Larsson
Ake
A
Nielsen
Boye Schnack
BS
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
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