Pathology and genetics of tumours of the urinary system and male genital organs

Epidermal growth factor-related peptides and their receptors in human malignancies

In October 1997, Dr. F.K. Mostofi assembled a group of individuals interested in bladder neoplasia at a meeting in Washington DC. The participants included urologic pathologists, urologists, urologic oncologists, and basic scientists with an interest in bladder neoplasia. The purpose of this meeting was to discuss bladder terminology and make recommendations to the World Health Organization (WHO) Committee on urothelial tumors. Following this meeting, a group of the urologic pathologists who attended the Washington meeting decided to broaden the representation of the group and arranged a meeting primarily of the members of the International Society of Urologic Pathologists (ISUP) at the 1998 United States and Canadian Academy of Pathology Meeting held in Boston. Massachusetts. At this meeting. issues regarding terminology of bladder lesions, primarily neoplastic and putative preneoplastic lesions, were discussed, resulting in a consensus statement. The WHO/ ISUP consensus classification arises from this consensus conference committee's recommendations to the WHO planning committee and their agreement with virtually all of the proposals presented herein. 29 The effort involved in reaching such a consensus was often considerable. Many of those involved in this process have compromised to arrive at a consensus. The aim was to develop a universally acceptable classification system for bladder neoplasia that could be used effectively by pathologists, urologists, and oncologists.

The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder

Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer

Although bladder cancers are very common, little is known about their molecular pathogenesis. In this study, invasive bladder cancers were evaluated for the presence of gene mutations in the p53 suppressor gene. Of 18 tumors evaluated, 11 (61 percent) were found to have genetic alterations of p53. The alterations included ten point mutations resulting in single amino acid substitutions, and one 24-base pair deletion. In all but one case, the mutations were associated with chromosome 17p allelic deletions, leaving the cells with only mutant forms of the p53 gene products. Through the use of the polymerase chain reaction and oligomer-specific hybridization, p53 mutations were identified in 1 to 7 percent of the cells within the urine sediment of each of three patients tested. The p53 mutations are the first genetic alterations demonstrated to occur in a high proportion of primary invasive bladder cancers. Detection of such mutations ex vivo has clinical implications for monitoring individuals whose tumor cells are shed extracorporeally.

https://science.sciencemag.org/content/sci/252/5006/706.full.pdf

Identification of p53 gene mutations in bladder cancers and urine samples

Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumours.

Summary— The UICC pT category for transitional cell cancer (TCC) of the bladder was recorded as assigned from the routine service of a pathology laboratory. All reports had been passed for release after review by pathologists of the status of senior registrar or above. After 99 cases had been collected, the slides available to the original pathologist were reviewed by one dedicated pathologist in continuous session who was ignorant of the original report. No new sections were cut. There was disagreement with the original report of pT category in 14 cases: 13 were downstaged (including 6 from invasive to superficial) and 1 upstaged. There was disagreement with the original differentiation grade in 13 cases: 10 TCC were considered to be more differentiated and 3 less differentiated than the original report.



A second pathologist reviewed the pT category only of 13 of the 14 cases, disagreeing with the original pT category on 8 occasions and with the pT category assigned by the dedicated pathologist on 7 occasions.



These findings have important implications for advising patients on prognosis and clinical management and in the design and reporting of therapeutic trials.

Differing interpretations by pathologists of the pT category and grade of transitional cell cancer of the bladder.

The indirect immunofluorescence technique was used to study the expression of the blood group A and H antigens in fresh-frozen and formalin-fixed paraffin-embedded sections of the bladder mucosa of 21 patients with non-neoplastic diseases of the bladder. Reliable assessment of these antigens could only be made using cryostat sections of fresh-frozen tissues. Also included in this study were tumour tissues of 5 patients with bladder cancer. The blood group A antigen was totally deleted in cryostat sections of the tumour of one patient with aggressive carcinoma and the appropriate antigens were diminished or focally deleted in the four patients with tumours that were non-invasive during one to three years of follow-up. It is concluded that sections of fresh-frozen tissues or sections processed in the absence of glycolipid-extracting solvents should be used for visualising the expression of blood group antigens in bladder tissues and assessing their value as prognosticators of the malignant potential of bladder tumours.

https://jcp.bmj.com/content/jclinpath/36/8/873.full.pdf

Blood group antigens in the normal and neoplastic bladder epithelium.

Summary— The detection of blood group antigens (BGA) in non-malignant prostates by previous workers has been at best inconsistent. BGA have not before been detected in prostatic carcinomas. In this preliminary study, a variety of anti-BGA reagents, with known specificities that involve the carbohydrate backbone in addition to the BGA specific terminal monosaccharides, were used to study the expression of the A and H(O) BGA in cryostat sections of 16 patients with benign prostatic disease and nine with prostatic cancer.



Positive staining, appropriate to the patients' blood group, was seen in all of the benign tissues when anti-BGA reagents that included specificity against type 2 backbone structures were used. Staining was absent, however, if the reagent had only type 1 specificity. The anti-A and anti-H(O) reagents which gave the best staining patterns in benign tissues were used in malignant tissues. No cancer was found to express A antigen but eight of the nine prostatic cancers were positive for the H (0) antigen irrespective of blood group.



Using fresh frozen material and appropriate reagents, BGA may be reproducibly detected in the epithelium of all non-malignant prostates, suggesting that a significant component of BGA is probably lipid-based on type 2 carbohydrate backbone chains. Further studies of changes in BGA expression in prostatic cancer are warranted.

Detection of blood group antigens in frozen sections of prostatic epithelium.

The attitude of 216 patients, 10 hospital doctors and 80 general practitioners (GPs) to hospital follow-up after uncomplicated surgery for non-malignant disease was assessed. Hospital doctors felt that most patients (86%) could have been satisfactorily followed-up by their GP and in most cases (89%), the GP was willing to provide the service. However, 183 patients (85%) found their visit to hospital out-patients worthwhile and only 41 patients (19%) would have preferred to have visited their GP instead. In fact, 157 patients (73%) had already seen their GP before their return to surgical out-patients. In most cases, hospital follow-up appears to be unnecessary. In this series, if suitable post-operative patients were followed-up by their GP, there would be a reduction of 20% in the number of old patients returning to out-patients.

P. D. Abel

Papers

Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumours.

Differing interpretations by pathologists of the pT category and grade of transitional cell cancer of the bladder.

Blood group antigens in the normal and neoplastic bladder epithelium.

Detection of blood group antigens in frozen sections of prostatic epithelium.

Attitudes to follow-up after uncomplicated surgery--hospital out-patients or general practitioner?