The molecular pathology of urological malignancies

Abstract

Urological malignancies kill over 16 000 people annually in England and Wales. There have been exciting recent developments in our understanding of the molecular pathogenesis of these diseases, although many questions remain unanswered. Three separate genes (WT1, WT2, and WT3) have been implicated in Wilms' tumour development. Patients with von Hippel–Lindau (VHL) syndrome develop renal cell carcinoma and it has been shown that VHL protein inhibits elongin, a cellular transcription factor which controls RNA elongation. Use of molecular markers to identify superficial bladder tumours likely to progress to muscle invasive disease has met with some success. Increased epidermal growth factor receptor (EGFR) and p53 expression, and decreased E‐cadherin expression all correlate with tumour progression. Tumours in patients with carcinoma in situ have distinct molecular features. Androgen ablation delays disease progression in men with prostate cancer, but relapse is inevitable. Research has been directed towards elucidating the mechanisms by which prostate cancer ‘escapes’ hormonal control. Mutations in the androgen receptor have been identified. It is apparent that locally produced growth factors mediate androgen‐dependent processes and these too have been implicated in prostate carcinogenesis. © 1997 John Wiley & Sons, Ltd.

Peptic Ulcer Disease and the Risk of Bladder Cancer in a Prospective Study of Male Health Professionals

“…On the basis of pathology reports, Ͼ90% of bladder cancer cases were transitional cell carcinomas. Carcinoma in situ tumors were included as these superficial lesions have a high risk of progression (18). Between 1986 and January 31, 2000, 414 incident bladder cancer cases were reported in this cohort.…”

Nonsteroidal antiinflammatory drug use and risk of bladder cancer in the health professionals follow‐up study

“…Carcinoma in situ tumors were included as cases as these superficial lesions have a high risk of progression. 48 Of the cases with stage information, 262 cases were early stage bladder cancer which included noninvasive and stage 1 bladder cancers and 123 cases were advanced stage bladder cancer which included bladder cancer cases that were stage 2 or higher.…”

Quantitative measurement of telomerase reverse transcriptase (hTERT) mRNA in urothelial cell carcinomas

“…Gross molecular alterations like DNA ploidy and several chromosomal abnormalities have been related to aggressive disease and progression of UCC (reviewed by Dorkin et al, 1997;Cordon-Cardo, 1998b;Kroft and Oyasu, 1994). Also, increased expression of p53 and epidermal growth factor receptor and decreased expression of E-cadherin have been identified as independent factors for prognosis (Dorkin et al, 1997;Cordon-Cardo, 1998b). Unfortunately, the sensitivity of these individual markers is still too low to be introduced in clinical practice, indicating the need for new markers.…”