Evaluation of HER2/neu and SPINK1 as an adjunct to the prognosis of urothelial dysplasia and urothelial carcinoma of the urinary bladder

Abstract

Background: Urinary bladder carcinoma is one of the most common malignancies worldwide. Urothelial carcinoma (UC) is the commonest type of bladder cancer and comprises 90% of all bladder primary tumors. Urothelial dysplasia (UD) points to urothelial instability and is a sign for tumor progression or recurrence, developing into UC in 5–19% of cases. Thus, the identification of valuable markers can be useful for assessing tumor progression and response to targeted therapies. Aim: This study aimed to assess the immunohistochemical expression of HER2/neu and SPINK1 in UD and UC, and their relation to available clinicopathological parameters. Materials and methods: This study was carried out on 30 cases of UD; and 30 cases of UC. Immunohistochemistry was performed using HER2/neu and SPINK1 primary antibodies Results: HER2 expression was positive in 3 cases of carcinoma in situ (CIS) (out of 30 cases of UD) and 17 out of 30 UC cases. SPINK1 showed positive expression in 2 CIS cases and 19 UC cases. There was a statistically significant difference in HER2 and SPINK1 expression between UD and UC. HER2 and SPINK1 expression increased significantly with the increased tumor size, grade and pathologic stage. Only HER2 expression was significantly associated with tumor recurrence. Conclusions: HER2 overexpression is closely associated with aggressive tumors. HER2 can be a valuable predictive indicator for UC prognosis selecting patients who are likely to benefit from anti HER2 targeted therapy. High SPINK1 expression also correlated with features of biologically aggressive bladder UC cases but did not have independent prognostic value.