THE EREXPRESSION OF P16 AND HER2/NEW BIOMARKERS IN BLADDER URETHRAL TUMOR AND ITS ASSOCIATION WITH HISTOPATHOLOGIC CHARACTERISTICS

Background & Aims: In addition to the clinical and histological factors that are able to differentiate between low grade tumors and high grade tumors in bladder urothelial tumors, a number of biomarkers have also been proposed that may be useful in evaluating tumor grade, outcome, and prognosis. The purpose of the present study was to investigate the relationship between the amount of Her2/neu and 16p markers with histological grade, prognosis, and recurrence of bladder urothelial carcinoma. Materials & Methods: In this cross-sectional study, paraffin blocks of 356 patients were collected. The tissue tumor points were selected from the main block and mounted on the tissue microarray (TMA) block of the receiver. Immunohistochemical staining was performed for Her2/neu and 16p markers. The intensity and extent of staining for these markers were determined by two pathologists using the combined and semi-quantitative method of histochemical score (H-Score). Results: The expression of Her2/neu in high and low grade tumors was significantly different from each other, so that the expression of Her2/neu based on H-Score in the group with high grade tumor was significantly higher than the low grade tumor (167.69 ± 103.77 against 93.16 ± 77.06) (P value = 0.001). According to the analysis of the area under the ROC curve, the Her2/neu marker expression had a significant value in distinguishing between high grade and low grade tumor cases (ROC=0.710, P=0.001). Accordingly, the best cut-off point for the above marker in differentiation of high and low grade tumors was 95, which had a sensitivity of 74.4% and a specificity of 55.2%. Expression of 16p marker in high and low grade tumors was not different (95.85 ± 120.68 and 92.36 ± 96.07; p>0.05), although it had a high value in predicting tumor prognosis. According to the results of multivariate logistic regression analysis and accounting other background factors of the study, the presence of a non-papillary pattern (probability ratio = 6.363; P = 0.001) was predictive of tumor recurrence.  Conclusion: By determining the H-Score, the Her2/neu marker will be able to distinguish high and low grade tumors from each other with acceptable sensitivity and specificity, and also, the 16p marker has a high value in predicting tumor prognosis.