Evaluating the utility of S100A7 in identifying oral dysplastic lesions that will progress to oral squamous cell carcinoma
Abstract
Title: Evaluating the utility of S100A7 in identifying oral dysplastic lesions that will progress to oral squamous cell carcinoma Introduction: Recently, S100A7 has been shown to be a potential useful marker for identifying oral lesions at risk of transformation from dysplasia to squamous cell carcinoma. Our hypothesis is that high S100A7 protein expression predicts the transformation of oral epithelial dysplasia to malignancy. The objective of our study is to semi-quantitatively evaluate the level of S100A7 expression in dysplastic lesions which have transformed into oral squamous cell carcinoma using immunohistochemistry, and correlate these results with other methods of analysis including the standard 3-tier histopathological diagnosis, the 2-tier histopathological diagnosis, and S100A7 evaluation utilizing StraticyteTM, a digital proprietary technique designed to communicate S100A7 expression in dysplastic tissue as a 5-year risk of malignant transformation. In addition, a pilot study evaluating the utility of QuPath, an open source software for bioimage analysis, will be assessed to determine if it more reliably correlates with the known outcomes of the sample populations. MAPK pathway proteins ERK1/2, p38, and JNK, will also be assessed for dysregulated phosphorylation in each of the sample populations.
Methods: Formalin fixed paraffin embedded specimens from 48 patients with oral squamous cell carcinoma, where from the same site, a non-cancerous biopsy had been previously obtained, were included in the study. Thirty five (35) patients with multiple biopsies of dysplasia which had not advanced to squamous cell carcinoma, and 25
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patients with a diagnosis of hyperkeratosis were included as control groups. In addition to the 3-tier dysplasia diagnoses of mild, moderate and severe, 2-tier diagnoses of low grade or high grade were assigned to each of the tissue samples. Specimens were stained for S100A7 protein using a standard immunohistochemistry protocol. Expression of S100A7 was assessed semi-quantitatively, using an intensity and proportion scale, as well as by image analysis using StraticyteTM and QuPath. As S100A7 is associated with activation of the MAPK signaling pathway activity, phosphorylated proteins ERK1/2, p38, and JNK were also evaluated via immunohistochemistry.
Results: Manual scoring of S100A7 stainingof epithelium in the three study populations was carried out and compared to the 3-tier and 2-tier grading schemes, StraticyteTM, and QuPath. Manual scoring had strong correlational relationships with QuPath and Straticyte based on Pearson correlation coefficients, and allowed differentiation of dysplastic from the Control groups. StraticyteTM, a test which utilizes a proprietary algorithm for the epithelial S100A7 stain assessment, allowed differentiation, of dysplastic tissue samples that progressed to OSCC, from those that did not (p < 0.05).
Conclusion: S100A7 holds potential for assisting in the identification of patients with oral premalignant lesions with dysplasia, that have an increased risk of malignant transformation as compared to those who do not.