High-molecular tenascin-C as an indicator of atypical cells in oral brush biopsies

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Abstract
Tumour-invasion like wound healing is characterised by the formation of an extracellular matrix with a high tenascin-C content. The tenascin-C molecule undergoes alternative splicing. Analysis using antibody BC2 indicates that especially the high-molecular tenascin-C (hm tn-C) variants are typically tumour-associated, while distribution in normal tissue is restrictive. This study investigated whether hm tn-C is a suitable indicator of atypical cells with invasive potential in oral brush biopsies. One hundred fifty nine consecutive oral brush biopsies with histopathological diagnoses were analysed for the identification of atypical cells. A standardised haematoxylin and eosin staining plus standardised immunocytochemistry using the monoclonal anti-hm tn-C antibody was performed. The bound hm tn-C antibodies were detected with the streptavidine/alkaline phosphatase technique in the autostainer. Conventional cytology produced four false-positives when identifying atypical cells in brush biopsies of inflammatory/benign hyperproliferative mucosa (specificity 96%), while 10 in 52 carcinomas and three of eight recurrences were not identified (sensitivity 78%). Ten of these 13 non-identified tumours could be marked when adding the hm tn-C assay (increasing specificity to 99%). Combining the two assays also reduced the false-positive outcomes from four to one (increasing sensitivity to 95%). The positive and negative predictive values were 92 and 88% for conventional cytology vs 98 and 97% for the dual assay. (1) A 95%-sensitivity proves hm tn-C assisted conventional cytology to be a suitable means of identifying atypical cells in oral brush biopsies. (2) The positive (98%) and negative (97%) predictive values obtained approximate hm tn-C assisted conventional cytology to laminin-5 (100/97%).