Abstract
BackgroundNon-muscle invasive bladder cancers (NMIBC: pTa, pT1) are characterised by a high risk of recurrence and/or progression. Identification of prognostic markers is needed to improve both diagnosis and management of the disease. The aim of this study was to analyse the expression of A-FABP (adipocyte-fatty acid binding protein) and to evaluate its prognostic value in bladder cancer with a long term clinical follow-up.MethodsA-FABP expression was investigated by immunohistochemistry in 236 tumours (114 pTa, 61 pT1, 61 pT2–4). Immunostaining was classified as negative (absent or weak immunostaining and moderate or strong staining on ≤10% of cells) or positive (moderate or strong staining on > 10% of cells). Event-free survival (EFS) and overall survival (OS) were determined with a 87.3 months median follow-up in the overall cohort. Recurrence-free survival (RFS) and progression-free survival (PFS) were established in NMIBC.ResultsLoss of A-FABP was associated with higher mean age, high stage/grade, and the presence of metastatic lymph nodes. It was correlated with shorter median EFS (17.5 vs 62.5 months; p = 0.001) and mean OS (76.7 vs 154.2 months; p = 0.009) and with higher risk of progression in the pTa/pT1 subgroup (HR, 0.36; 95% CI, 0.13–0.96; p = 0.041) and importantly in the pTa tumours (HR, 0.34; 95% CI, 0.10–0.97; p = 0.045).ConclusionThese results demonstrated that loss of A-FABP expression following a long follow-up was predictive of pTa and pTa/pT1 progression. Immunohistochemistry on diagnostic biopsy is easy to use and could be of value to help clinicians to propose appropriate treatment for these tumours.
Highlights
Non-muscle invasive bladder cancers (NMIBC: papillary tumours confined to the mucosa (pTa), pT1) are characterised by a high risk of recurrence and/or progression
Contrary to what we have demonstrated in bladder cancer, where strong expression of A-fatty acid binding proteins (FABPs) was associated with a good prognosis, high A-FABP expression was significantly associated with shorter disease-free survival and overall survival (OS) in breast cancer patients [18]
Unlike the studies described above reporting the expression of A-FABP protein by immunohistochemical or two-dimensional electrophoresis analyses, we show on a long-term follow-up of patients that high expression of A-FABP was associated with a good prognosis and that the decrease of A-FABP expression is a tumor progression marker of pTa and pTa/pT1 group
Summary
Non-muscle invasive bladder cancers (NMIBC: pTa, pT1) are characterised by a high risk of recurrence and/or progression. Identification of prognostic markers is needed to improve both diagnosis and management of the disease. 75% are non-muscle invasive bladder cancers (NMIBC). They include carcinoma in situ (Cis) and papillary tumours confined to the mucosa (pTa) or lamina propria (pT1). In the NMIBC patient group, as many as 50 to 80% of cases with low grade pTa-pT1 will recur, and up to 40 to 50% of cases with high grade/G3 pTa-pT1 or associated Cis will progress within 5 years to a higher tumour stage or metastatic disease [4]. Patients with bladder urothelial carcinoma should be carefully monitored for signs of disease recurrence or progression. Molecular prognostic markers of tumour recurrence and progression are urgently needed to improve our understanding, diagnosis and management of UC
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