Expression of prostate-specific membrane antigen in renal cortical tumors.

Prostate-specific membrane antigen is a type II membrane glycoprotein that is expressed in benign and neoplastic prostatic tissue and has been recently shown to be also expressed in the neovasculature of various solid malignant tumors including renal cell carcinoma. Renal cell carcinoma is a heterogeneous group of tumors with distinct morphologic and genetic characteristics and clinical behaviors. We performed immunohistochemical studies on formalin-fixed, paraffin-embedded archival material from 75 nephrectomies, using antibodies 13D6 against prostate-specific membrane antigen and CD31 against endothelial cells. The study included 30 clear cell renal cell carcinomas, and 15 of each of papillary and chromophobe renal cell carcinoma and oncocytoma. The extent and intensity of staining were assessed semiquantitatively. In all cases, immunoreactivity was detected only in the tumor-associated neovasculature and not in tumor cells. Clear cell renal cell carcinoma showed the most diffuse staining pattern, where 24/30 cases or 80% had >50% reactive vessels, followed by chromophobe renal cell carcinoma (9/15; 60%) and oncocytoma (5/15, 33%). No diffuse staining was detected in any of the papillary renal cell carcinomas and only focal staining was detected in 11 cases (11/15; 73%). Staining intensity was the strongest in clear cell renal cell carcinoma (25/30; 83%) followed by chromophobe renal cell carcinoma (9/15; 60%), oncocytoma (8/15, 53%) and papillary renal cell carcinoma (5/15; 33%). In summary, prostate-specific membrane antigen is expressed in tumor-associated neovasculature of the majority of renal cortical tumors and is most diffusely and intensely expressed in clear cell renal cell carcinoma and least in papillary renal cell carcinoma. The differences in the expression of prostate-specific membrane antigen in renal cell carcinoma subtypes provide further evidence of the biological diversity of these tumors, and diagnostic and therapeutic applications of such expression can be expanded to include subtypes of renal cell carcinoma.     

Glomus tumor of the kidney: a report of 3 cases involving renal parenchyma and review of the literature

Glomus tumor is a rare mesenchymal neoplasm affecting the subcutaneous tissue of the distal extremities in the majority of cases. It only rarely involves visceral organs. We report 3 cases of the glomus tumor family in the kidney, a solid glomus tumor, a glomangioma, and a glomangiomyoma. All 3 tumors involved the renal parenchyma and occurred in 3 men aged 36, 81, and 48 years, respectively. All 3 tumors were well-circumscribed and showed morphology otherwise identical to those seen in soft tissue. All 3 tumors were immunoreactive for actin and negative for desmin and S100 and only 1 tumor expressed CD34 in tumor cells. To date, all 3 tumors have followed a benign course without evidence of recurrence or metastasis. This report expands the spectrum of mesenchymal tumors of the kidney.     

Bladder cancer in cystoscopically normal‐appearing mucosa: a case of mistaken identity?

Study Type – Diagnosis (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To test the frequency of malignancy in normal‐appearing urothelium in patients with high‐risk bladder cancer, as biopsy of normal‐appearing mucosa using standard white‐light cystoscopy (WLC) reportedly shows carcinoma in situ (CIS) in some patients with bladder tumours.

PATIENTS AND METHODS

Cold‐cup biopsies of normal‐appearing mucosa were obtained by two experienced oncological urologists from 63 patients during transurethral resection of bladder cancers. Each biopsy labelled as ‘normal’ was interpreted by two expert uropathologists.

RESULTS

Each of the biopsies in all 63 patients was interpreted by both urological pathologists as showing normal or benign histology, except that one showed focal CIS.

CONCLUSIONS

Bladder urothelium appearing normal to expert urological oncologists using standard WLC rarely shows CIS when biopsies are evaluated by experienced uropathologists.     

Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy

Objectives

To determine the incidence and location of prostate adenocarcinoma (PCa) and prostatic urothelial carcinoma (PUC) for patients undergoing radical cystoprostatectomy (RCP) for bladder cancer and to ascertain what preoperative information may be useful in predicting PUC or PCa in patients who may be candidates for prostate-sparing cystectomy.

Methods

Between 2001 and 2004, 235 consecutive patients underwent RCP and had whole-mount sections of the prostate. We reviewed our prospective radical cystectomy database for preoperative clinicopathological information associated with each patient. The bladder and whole-mount prostate sections were re-reviewed to determine the location and depth of the bladder tumor as well as the presence of any associated PCa and PUC.

Results

We identified 113 of 235 (48%) and 77 of 235 (33%) men with PCa and PUC, respectively. Among patients with PCa, 33 (29%) had Gleason score of ≥ 7, 25 (22%) had PCa tumor volume > 0.5 cc, and 15 (13%) had extracapsular extension. On multivariable analysis, only increasing age was significantly associated with PCa (odds ratio = 1.3, p = 0.046). Of the 77 with PUC, 28 (36%) had in situ disease only, while 49 (64%) had prostatic stromal invasion. Bladder tumor location in the trigone/bladder neck (p < 0.001) and bladder carcinoma in situ (p < 0.001) was strongly associated with PUC in the final specimen. Overall, 158 (67%) had either PCa or PUC in the prostate.

Conclusions

PCa and/or PUC is present in a majority of RCP specimens. Current preoperative staging and tumor characteristics are not adequate for determining who can safely be selected for prostate-sparing cystectomy.     

Hypoxia‐inducible factor and mammalian target of rapamycin pathway markers in urothelial carcinoma of the bladder: possible therapeutic implications

What’s known on the subject? and What does the study add? The hypoxia‐inducible factor (HIF) and mammalian target of rapamycin (mTOR) pathways are important in tumorigenesis and novel agents targeting these respective pathways have shown promising activity in several malignancies. The current study demonstrates the expression of HIF and mTOR related pathway markers in urothelial carcinoma providing a rationale for clinical trials evaluating agents targeting these pathways.

OBJECTIVE

To investigate the rationale for using targeted therapies against hypoxia‐inducible factor (HIF) and mammalian target of rapamycin (mTOR) pathways in urothelial carcinoma of the bladder, by studying the immunohistochemical expression of molecules of these pathways in urothelial carcinoma, as recent pre‐clinical studies and clinical trials have shown the potential utility of such targeted therapies.

PATIENTS AND METHODS

Immunohistochemical stains were performed on a tissue microarray prepared from 92 cases of ≥ pT2 urothelial (transitional cell) carcinoma of bladder, using antibodies against HIF‐1α and VEGF‐R2, and phospho‐S6 and phospho‐4E BP1, molecules of HIF and activated mTOR pathways, respectively. Immunoreactivity was graded from 0 to 3+ (0, 0–5%; 1+, 6–25%; 2+, 26–50%; 3+, > 50% tumour cells positive).

RESULTS

In all, 58, 34, 35 and 17% of the tumours showed grade 2–3+ expression of phospho‐4E BP1, phospho‐S6, HIF‐1α and VEGF‐R2, respectively. Moderate correlation for immunoreactivity was observed between molecules within the same pathway [(phospho‐4E BP1 with phospho‐S6 (rho = 0.411), and HIF‐1α with VEGF‐R2 (rho = 0.265)], but not between molecules across pathways.

CONCLUSIONS

Urothelial carcinomas of the bladder express molecules of the HIF and mTOR pathways, providing a rationale for clinical trials evaluating agents targeting these pathways. Correlation between molecules within the same pathway, and not across pathways, suggests that investigating the usefulness of a specific targeted agent might benefit from pre‐treatment evaluation of pathway marker expression.