Cystectomy is the prime treatment of muscle-invasive urothelial carcinoma but it is associated with many complications and affects patients’ quality of life. Chemotherapy is an alternative modality, but it may not give the expected response. This arouses the need for markers that help to predict the response to chemotherapy. Her2-neu, Skp2 and HIF-1 regulate cell cycle progression, tumor adaptation to hypoxic environment and response to chemotherapy.
This study aimed at evaluation of HER2-neu, SKP2 and HIF1 expression in muscle-invasive urothelial carcinoma and investigating the association between their expression and tumor response to chemotherapy.
Patients & Methods
One hundred specimens of non-metastatic muscle-invasive urothelial carcinoma were collected at Pathology department and the selected patients received the treatment and followed up at Clinical Oncology Department, Menoufia University. HER2-neu, SKP2 and HIF-1expression were evaluated using immunohistochemical techniques. The patients received chemotherapy followed by cystoscopic examination. Bladder biopsy was examined to determine tumor response.
A significant association was found between partial tumor response to chemotherapy and HER2-neu, SKP2 and HIF-1 positive expression (P=0.004, 0.029 and 0.004,). Skp2 expression was significantly associated with low apoptotic count and high mitotic one (P= 0.008 and 0.01), while HIF-1 expression was significantly associated with necrosis (P=0.008). A statistically significant association was found between Skp2 and HR2-neu expression (P= 0.018) and between SKP2 and HIF-1 expression as well (P= 0.013).
This study showed that HER2-neu, SKP2 and HIF-1expression can predict poor response to chemotherapy in muscle-invasive urothelial carcinoma and helps in selecting patients who will benefit from chemotherapy .In addition, target therapy against these markers can be effective in treatment.