Loss of Expression of the Adipocyte-type Fatty Acid-binding Protein (A-FABP) Is Associated with Progression of Human Urothelial Carcinomas

Abstract

Bladder cancer is the second most common genitourinary tumor and the fourth most common solid malignancy in Denmark, with an incidence of 1,200 -1,300 patients per year and a mortality rate of ϳ300. It encompasses a large variety of histological heterogeneous tumor types arising predominantly in the epithelium (urothelium) lining of the urinary bladder and the ureters. Tumor types of the urothelium include urothelial carcinomas (UCs), 1 squamous cell carcinomas, adenocarcinomas, as well as other less frequent lesions (1). UCs account for more than 90% of the bladder carcinomas and comprise a wide spectrum of lesions with distinct biological and functional characteristics. Up to 80% of patients with superficial bladder cancer lesions will recur, and of these ϳ25% will progress to invasive disease (2). A major challenge today is to identify the subset of low-grade lesions that may recur and evolve into muscle invasive and subsequently to metastatic disease.Presently, the most reliable prognostic factors for recurrence and progression are grading and staging. These parameters, however, cannot predict with certainty the long-term outcome of the disease, and as a result it is important to devise strategies to identify biomarkers that may predict tumor behavior and clinical outcome. Several prognostic markers have been identified, some of which, like p53 and pRB, have a long-standing association with bladder cancer (3, 4). The product of the retinoblastoma gene (pRB) is a main regulator of cell-cycle progression, while p53 exerts its function as a key DNA checkpoint molecule, triggering growth arrest or apoptotic processes in response to DNA aberrations and cellular stress. pRB and p53 are frequently altered in bladder From the ‡Department

Adipocyte fatty acid-binding protein as a novel prognostic factor in obese breast cancer patients

“…In keeping with the earlier data showing a positive correlation between serum A-FABP levels and BMI [13,[25][26][27][28][29] the mean serum levels of A-FABP in our cohort are significantly higher in obese women than in normal weight women, independent of menopausal status. The range of serum A-FABP levels in our study, between 14.15 and 59.1 ng/ml, is comparable to those reported by Yeung et al [28], Stejskal et al [27], and Möhlig et al [13] (17.0 to 41.9 lg/L, 23.7 to 42.4 lg/L, and 5.1 to 113.0 ng/ml, respectively).…”

“…Therefore, our findings rather support that obesity by itself is associated with breast cancer risk, and that postmenopausal HRT use was a non-confounding factor in our patients. Several data suggest the influence of A-FABP expression on urothelian and prostate cancer development [15,24,25]; however, data regarding A-FABP and breast cancer risk are scarce and controversial. Hammamieh et al [15] showed significant lower serum levels of A-FABP mRNA in human breast cancer cells lines compared with normal breast cells.…”

A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

“…3 Loss of A-FABP protein has been convincingly identified as a marker of progression of human bladder TCC. 4 Most of the published data are related to A-FABP protein expression using a combination of proteomic technologies. In the present work, after optimizing a method of A-FABP mRNA quantification by real-time RT-PCR, we demonstrated a significant decrease of A-FABP mRNA levels according to the tumor stage and the histologic grade of bladder TCC.…”

“…4 We evaluated and compared A-FABP transcript levels by real-time RT-PCR from 26 bladder cancer patients according to the tumor stage and to the histologic grade. We chose as reference a non-invasive low-grade pTa tumor expressing the epithelial marker E-cadherin but not the mesenchymal marker Ncadherin.…”

“…2,3 The loss of A-FABP protein expression has been associated with bladder cancer progression and could have a significant prognostic value. 4 These data suggest that A-FABP could be a novel marker with potential clinical utility to select patients that are more likely to develop aggressive disease.…”