P.M.J. Moonen

REVIEW PATHOLOGY IN A DIAGNOSTIC BLADDER CANCER TRIAL: THE IMPACT OF PATIENT RISK CATEGORY

Abstract Objectives Bladder cancer pathologic features are a continuous spectrum from benign to invasive lesions, causing diagnostic difficulties. Review pathology might be an answer, but appears to be of limited value. We studied the effect of patients’ risk profile on the value of review pathology. Methods We used three Phase III multicenter studies that assessed the value of hexaminolevulinate fluorescence cystoscopy on diagnosis and management. Two studies (Europe and United States) included patients at high risk of carcinoma in situ (CIS), the third study (Europe) included all patients at risk of bladder cancer. Tumors and biopsies were examined by a local and review pathologist. Results The percentage of patients with CIS was high in the first two studies (20.6% and 15.9%) compared with the epidemiologic data (7.9%) and the third study (7.8%). The numbers of patients (specimens) in the three studies were 209 (927), 277 (986), and 142 (553). Overall conformity for both grade and stage was between 50.5% and 56.6%, comparable to published data. Although conformity was best in the high-risk study, this was predominantly because of the better conformity in low-risk tumors. Conformity in Stage T1, CIS, and invasive tumors was low. The results from Europe and the United States were comparable, although the local pathologist in the United States tended to overstage or overgrade. Conclusions Although histologic conformity was greater in the high-risk patient population, this was mainly a result of pTa tumors. The diagnosis of pT1, CIS, and invasiveness appears difficult. Because these tumors significantly influence therapy, review pathology in patients at high risk or suspicious for high risk should be considered.

Components of the plasminogen activator system and their complexes in renal cell and bladder cancer: comparison between normal and matched cancerous tissues

To analyse and compare the concentration of plasminogen activator (PA), urokinase‐type PA (uPA), tissue‐type PA (tPA), PA inhibitor (PAI)‐1 and PAI‐2, and the complexes uPA‐PAI‐1 and tPA‐PAI‐1 and calculated uPA and tPA uncomplexed with PAI‐1 (‘free’) in urothelial cell carcinoma and matched benign urothelium, and in renal cell carcinoma (RCC) and matched benign renal tissue.

False-positive lesions detected by fluorescence cystoscopy: any association with p53 and p16 expression?

To determine p53 and p16 status as molecular markers of bladder cancer, in histologically proven benign bladder biopsies, obtained from lesions suspect for malignancy as judged by fluorescence cystoscopy. Immunohistochemical (IHC) staining was performed for p53 and p16, using the antibodies DO-7 and AB-4, respectively. The tissue sections were scored in percentages of nuclear staining for p53 and p16. Of 247 biopsies, 41/49 lesions appeared suspicious on fluorescence cystoscopy, but were histopathologically benign. 2/40 (5%) were ≥20% p53 positive as compared to 7/128 (5.5%) of all histopathologically benign biopsies. 24/37 (64.9%) were p16 negative (<5% positive cells) as compared to 84/125 (67.2%) of all benign biopsies. Most biopsies had a moderate to high degree of chronic cystitis. False positive lesions of fluorescence cystoscopy did not differ from benign lesions detected by standard white light cystoscopy with regard to p53 and p16 immunoreactivity. Little evidence remains for these lesions to be pre-malignant.