Low level STK15 amplification in histologically benign urothelium of patients with bladder cancer adversely predicts patient outcome following cystectomy

Abstract

Abstract. The aim of this study was to investigate STK15 amplification in histologically benign urothelium and invasive tumor tissue of urothelial bladder cancer patients in relation to clinicopathologic and molecular characteristics, and to analyze a hypothesized association between the STK15 single nucleotide polymorphism at site T91A (Phe31Ile) and STK15 gene amplification. A tissue microarray (TMA) was constructed and contained formalin-fixed paraffin-embedded tumor tissue and matching histologically benign urothelium of 44 patients who underwent cystectomy for invasive urothelial carcinoma. Expression of TP53, CK20 and MIB1 was evaluated by immunohistochemistry. UroVysion and STK15 fluorescence in situ hybridization (FISH) analysis was performed for sensitive detection of polysomy, relative p16 deletion and STK15 amplification, respectively. Genotypes of STK15 at the T91A (Phe31Ile) site were analyzed by PCR-RFLP assay. Low level STK15 amplification was found in 2 of 36 analyzable histologically benign urothelium specimens (5.6%) and in 64% (28/44) of urothelial bladder cancers, whereas 36% (16/44) of cancer lesions showed high level of STK15 amplification. In histologically benign urothelium of bladder cancer patients, low level STK15 amplification was associated with shorter recurrence-free and tumor-specific survival. There was no correlation between allelic variants and high/low level of STK15 gene amplification. Applying STK15 FISH to benign urothelium of bladder cancer patients may help to identify patients at increased risk for adverse clinical outcome. A large randomized prospective study comparing early versus delayed cystectomy in patients with pT1 bladder cancer is currently conducted to validate our findings.

Aurora-A signaling is activated in advanced stage of squamous cell carcinoma of head and neck cancer and requires osteopontin to stimulate invasive behavior

“…Our data showed that overexpressed Aurora-A protein in most HNSCC tumor tissues was primarily distributed in the cytoplasm compared to that found in nucleus of tumor (~10-15%) and the adjacent non-tumor tissues (~5-10%). Similar finding also observed in other human cancer tissues, such as bladder, colorectal and ESCC[5, 43, 44]. In contrast to these studies, several reports indicated that Aurora-A accumulated in the nucleus and associated with advanced cancer stage[1, 37].…”

Bladder cancer SNP panel predicts susceptibility and survival

“…Allelic variation in AURKA has been associated with AURKA expression levels and increased risk of multiple cancers in a meta-analysis of 9,549 cases (Ewart-Toland et al 2005; Matarasso et al 2007). AURKA amplification is very prevalent in bladder tumors (64%) and tumor AURKA gene and protein expression levels are associated with tumor recurrence and shorter survival time (Comperat et al 2007; Denzinger et al 2007; Schultz et al 2007). The previously examined AURKA polymorphism T91A was not associated with bladder cancer prognosis in a study of 135 patients (Schultz et al 2007).…”

Complementary Tumor Diagnosis by Single Cell–Based Cytogenetics Using Multi‐marker Fluorescence In Situ Hybridization (mFISH)

“…The significant advantage of FISH (i.e., the use of fluorophore‐labeled probes) over ISH (i.e., the use of chromogenic labeled probes) is the ability to apply and visualize more than two probes simultaneously, which results in a multi‐color (i.e., multi‐marker) hybridization (mFISH). In this way, multiple regions located on the same chromosomes or on different chromosomes can be addressed and analyzed at the same time (Denzinger et al., 2007; Miyake et al., 2023; Pothos et al., 2008; Schwarz et al., 2004; Schwarz et al., 2008). Additionally, individual markers can be visualized and assessed separately or simultaneously by using microscopic single‐color or dual‐ or even three‐color filters.…”