The Prognostic Significance Of Her2/Neu, P27 And Sonic Hedgehog Proteins In Urothelial Cell Carcinoma Of The Bladder In Saudi Arabia.

e16020 Background: Urothelial bladder carcinoma (BC) is characterized by high recurrence ratio and greater risk for progression to invasive form that necessitates regular surveillance to monitor disease recurrence. Therefore, there is an urgent need for a reliable biomarker that could be used in clinical setting to assist with the current staging and grading systems to accurately predict for BC progression. The aim of the current study was to analyze the status of her2/neu, p27 and sonic hedgehog (SHh) expression and their clinical value as a prognostic markers in BC. Methods: Formalin-fixed paraffin-embedded BC samples were collected from patients who underwent surgical resection at King Abdulaziz University Hospital- KSA. One hundred and sixty samples were arranged on a tissue microarray (TMA) and stained with anti-her2, p27 and SHh antibodies using immunohistochemistry (IHC). Her2 gene amplification was evaluated using bright-field dual in situ hybridization (BDISH) method. The results were correlated with clinicopathological parameters and survival. Results: Immunostaining of BC TMA revealed that Her2, p27 and SHh proteins are expressed in 85%, 50% and 76% respectively of the analyzed BC cohort. Overexpression of her2 (3+) was observed in 24% and significantly associated with tumour staging (p= 0.002), lymph node invasion (p= 0.04) and vascular invasion (p= 0.01). BDISH revealed that her2 gene is amplified in 25% of patients and significant correlation with tumour grade (p= 0.03). p27 expression inversely correlates with tumour grade (p= 0.001) and muscle invasion (p= 0.014). Positive correlation between the level of SHh expression and lymph node metastasis (p= 0.02) and poor cancer-specific survival in BC (p < 0.04, log-rank test). Conclusions: The expression of her2, p27 and SHh was correlated with the invasive phenotype of BC and might serve as potential markers for cancer metastasis and poor prognosis. This finding indicates that high proportion (24%) of BC patients could potentially benefit fron anti-her2 targeted therapy. Acknowledgement: The authors thank King Abdulaziz City for Science and Technology for the financial support to the project (ات-33-26).