ONCOFETAL FIBRONECTINS IN ORAL CARCINOMAS - CORRELATION OF 2 DIFFERENT TYPES

Different isoforms of fibronectin are derived from a single gene by al ternative processing of the primary RNA transcript or by posttranslati onal modifications. We have previously demonstrated that an oncofetal fibronectin (FN) isoform derived by O-glycosylation is highly associat ed with malignancy in breast and oral tumors. Another oncofetal FN iso form containing the ED-B sequence is derived by alternative splicing, and FN containing ED-B has been found to be a stromal marker of malign ancies in various tissues. Here we report a comparative study by immun ohistology of the distribution of the ED-B-containing isoform and the oncofetal FN isoform derived by O-glycosylation, in oral squamous cell carcinomas, premalignant lesions, and normal oral mucosa. A selective expression of the ED-B-containing isoform was demonstrated in close r elation to the invading carcinoma (38/38), whereas there was virtually no staining in submucosa underlying premalignant lesions (1/11) and n ormal epithelium (0/5). The ED-B-containing FN showed close co-distrib ution and staining pattern with the oncofetal isoform derived by O-gly cosylation. These results demonstrate that accumulation of FN adjacent to oral carcinomas includes both the ED-B-containing isoform and the isoform derived by O-glycosylation. Although both the change in primar y structure and glycosylation of FN create conformational and immunolo gically detectable changes, the functional consequences in association with invasive carcinoma are poorly understood at present. Diagnostic implications especially of borderline lesions as well as evaluation of tumor aggresiveness may, however, be important.