A NEW HIGH-RESOLUTION INVASION TEST (HIT) CAN PREDICT MALIGNANT TRANSFORMATION IN ORAL EPITHELIAL DYSPLASIAS

Rationale Detecting the earliest signs of invasion and predicting transformation in oral potentially malignant lesions (OPMLs) can facilitate earlier treatment of oral squamous cell carcinoma (OSCC) and decrease morbidity and mortality. Here we described a new test to diagnose early invasion and predict malignant transformation in OPML. Methods Fluorescent immunohistochemist and multichannel colocalization were used to identify invadopodia markers FISH, cortactin and MMP14 in OSCC and OPML. The presence of invadopodia markers was calculated using 3-channel colocalization analysis based on a custom algorithm developed using Volocity Software. The threshold for colocalization was determined by linear least-square fit of the channel intensities and the product of the difference of the means was (PDM) was used to compare the area of colocalization (HIT score). This algorithm was applied to 80 cases (10 cases of non-dysplastic hyperkeratosis, 22 cases of epithelial dysplasias (ED), 20 cases of OSCC and 28 cases from patients who progressed from ED to OSCC) to determine the overall validity of the approach and establish cut off values. Results There was a significant and progressive increase in the colocalization of invadopodia markers (HIT score) in dysplasias and OSCC compared to control. The results showed that the HIT score could detect lesions that transformed to OSCC independently of the histopathological diagnosis with a sensitivity of 84% and specificity of 61.76%, PPV= 0.61 and NPV=0.84, AUC= 0.7653, likelihood ratio of 2.1, p Conclusion The HIT scores can predict malignant transformation in oral biopsies independent of the histopathological diagnosis. Larger prospective studies are needed to validate and assess the applicability of this test in combination with conventional histopathology.