Search PubMed⌕ Search

Biomedical subjects

D G Bostwick

Publications and source records attributed to D G Bostwick.

At least 91 records · Page 5Linked to original sources
PubMed1999

Overexpression of the wild type p73 gene in human bladder cancer.

p73, a first p53 relative, was recently identified and shown to be monoallelically expressed in a number of different human tissues. To determine the potential role of this gene in human bladder cancer, we investigated p73 expression levels, allelic expression patterns, and analysed p73 mutations in 23 unselected primary invasive bladder cancers with matched normal tissues and in seven bladder cancer cell lines. In a comparison between normal and tumor tissues using quantitative RT-PCR analysis, we found that p73 was overexpressed in 22/23 bladder cancers, sometimes as great as 20-fold. Allelic expression analysis using a C/T polymorphism in exon 2 and a newly identified T/C polymorphism in exon 5 revealed that p73 was biallelically expressed in both normal bladder and cancer tissues, suggesting that p73 is not imprinted in bladder tissue. Mutation screening of the p73 gene in bladder cancer DNAs using denaturing high-performance liquid chromatography analysis and DNA sequencing revealed no tumor-specific mutations in any coding exons of the p73 gene. These data suggest that the p73 is unlikely to be a tumor suppressor gene, but that overexpression of p73 may contribute to tumorigenesis in bladder cancer.

Alleles↗
PubMed1999

Mutation and expression analysis of the p73 gene in prostate cancer.

BACKGROUND: p53 is the most highly mutated tumor suppressor gene in human cancers. Recently, p73, a first homologue of p53, was identified and considered to be an imprinted tumor suppressor gene. Thus, we analyzed the possible role of p73 in human prostate cancers. METHODS: We investigated the expression levels and expressed allelotypes and searched for mutations in the p73 gene in 27 primary prostate cancers with matched normal tissues as well as in four prostate cell lines. RESULTS: Allelic expression analysis using polymorphisms in exons 2 and 5 revealed that p73 is biallelically expressed in both normal and tumor tissues, suggesting that p73 is not imprinted in prostate tissues. Quantitative PCR demonstrated that p73 expression is the same in both normal and tumor prostate tissues. Denaturing high-performance liquid chromatography and DNA sequencing revealed that there were no tumor-specific mutations in the p73 gene at the genomic level. CONCLUSIONS: These data indicate that alterations of p73, including mutations, changes in message abundance, and changes in allelic expression, are likely to be rare in early-stage prostate cancer, and that p73 could be a tissue-specific imprinting gene.

DNA Mutational Analysis↗
PubMed1999

Cystic renal cell carcinoma is cured by resection: a study of 24 cases with long-term followup.

PURPOSE: The true incidence and biological behavior of cystic renal cell carcinoma are not known. To our knowledge we present the largest series of patients with cystic renal cell carcinoma with long-term followup. MATERIALS AND METHODS: We reviewed the Mayo Clinic surgical pathology files of renal cell cancer cases with a cystic component resected from 1969 to 1997, and arbitrarily chose 75% tumor involvement by cysts as a cutoff for inclusion in the study. RESULTS: We identified 24 cases of clear cell renal cell carcinoma with 75% or greater involvement by cysts comprising 0.79% of 3,047 renal cell cancer cases resected at our institution between 1969 and 1997. Mean patient age was 62.7 years (range 40 to 83). A total of 11 patients (46%) underwent radical nephrectomy, 4 (17%) simple nephrectomy, 3 (12%) partial nephrectomy and 6 (25%) tumor enucleation. Mean tumor involvement by cysts was 84% (range 75 to 95) and in 11 cases (46%) involvement was 90% or greater. Cancer stage was T1 in 20 patients (83%), T2 in 1 (4.4%) and T3a in 4 (12.5%). Cancers were diploid in all but 1 case. Mean followup was 77.6 months (range 8 to 428, median 51). A total of 22 patients (92%) had no evidence of cancer and 2 died of intercurrent disease. CONCLUSIONS: Our results indicate that cystic renal cell carcinoma is uncommon and usually cured by resection, regardless of size, stage or number of cysts. These patients may benefit from nephron sparing surgery, such as partial nephrectomy.

Adult↗
PubMed1999

Demonstrability of the glycoprotein A-80 in postradiation prostatic carcinoma.

Radiation therapy results in significant morphological changes in prostatic carcinoma, including decreased cancer size, acinar shrinkage and distortion, cytoplasmic vacuolization, and nuclear pyknosis. Benign acini usually display enlarged, atypical cells with hyperchromatic nuclei. These changes confound the evaluation of limited postradiation samples. The glycoprotein A-80 is known to be upregulated in prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma. In this study, we assessed the expression of A-80 in radiation-treated prostatic carcinoma. Paraffin sections from 64 postradiation prostatic carcinomas obtained at salvage prostatectomy were immunostained with a monoclonal antibody to A-80; selected sections were doubly immunostained with antibodies to A-80 and various cytokeratin polypeptides. All cases showed readily detectable and often intense staining in the cytoplasm of cancer cells and in intraluminal material of malignant acini. The extent and intensity of the reactions were independent of cancer size and grade. Strong reactions were seen in preserved and distorted acini, clear cell areas, single cancer cells, and in colloid pools with few or no recognizable cancer cells. PIN was present in 34 cases (53%), of which 27 (79%) stained strongly for A-80; atrophic and hyperplastic acini generally did not stain, irrespective of the degree of cellular atypia. The A-80 glycoprotein appears remarkably durable and is readily demonstrable in postradiation prostatic carcinoma despite profound architectural and cytologic changes. This characteristic may prove useful in evaluating small samples for confirmation of diagnosis and determination of extent of residual or recurrent prostatic carcinoma after radiation therapy.

Aged↗
PubMed1999

Subepithelial pelvic hematoma of the kidney clinically mimicking cancer: report of six cases and review of the literature.

OBJECTIVES: Renal pelvic subepithelial hematoma is a rare but significant clinical mimic of neoplasm. Investigation and treatment of this diagnostic problem are uncertain. METHODS: We add 6 patients with this entity to the 15 previously published cases. All 6 were clinically suspected of having cancer, and 5 underwent nephrectomy. RESULTS: The most common clinical findings are gross hematuria (19 of 21 cases) and acute onset of flank pain (13 of 21 cases). Intravenous urogram usually reveals a filling defect at the ureteropelvic junction. Pathologic findings include massive subepithelial and peripelvic hemorrhage, hydronephrosis, cortical infarcts, and renomegaly. Two of our patients have previously undescribed clinical associations, including one who was 2 weeks postpartum and another with ureteropelvic junction obstruction. In addition, our patient with obstruction is the first with subepithelial hematoma to be treated successfully with pyeloplasty. CONCLUSIONS: Subepithelial pelvic hematoma may be effectively treated with pyeloplasty or partial nephrectomy if distinguished from cancer preoperatively. Awareness of this rare entity may allow preoperative identification, but this has not been possible to date.

Adult↗
PubMed1999

Clinically unsuspected and undetected (clinical stage t0) prostate cancer diagnosed on random needle biopsy.

OBJECTIVES: To describe the findings in 4 patients who underwent radical prostatectomy for clinically undetected and unsuspected prostate cancer detected on random needle biopsy. METHODS: We reviewed the Mayo Clinic Radical Prostatectomy Prostate Cancer Database of 5793 prostatectomies from 1987 to 1997, and identified 4 patients who had prostate cancer detected on random needle biopsy of the prostate with serum prostate-specific antigen (PSA) less than 4 ng/mL and normal digital rectal examination. Each had requested biopsy despite the absence of clinical suspicion of cancer; 3 had normal transrectal ultrasound, and the fourth had a benign hypoechoic lesion contralateral to the cancer. RESULTS: Mean patient age at diagnosis was 65.5 years (range 61 to 67). Mean PSA was 2.4 ng/mL (range 2 to 2.9). Mean tumor volume was 3 cc (range 0.04 to 11.2). Mean Gleason grade at prostatectomy was 5.75 (range 5 to 7). Prostate cancer was Stage T2a in 1 patient (25%), T2c in 2 (50%), and T3a (25%) in 1. Three tumors were DNA diploid, and one was aneuploid. All patients were alive without evidence of cancer at a mean follow-up of 43 months (range 25 to 53) with undetectable serum PSA concentration. CONCLUSIONS: Our findings indicate that clinically unsuspected and undetected (clinical Stage T0) prostate cancer may be clinically significant. Patient insistence on biopsy reflects increasing concern among the public about prostate cancer. Current clinical thresholds for biopsy detection will fail for some patients with clinically significant prostate cancer.

Aged↗
PubMed1999

Human glandular kallikrein 2 expression in prostate adenocarcinoma and lymph node metastases.

OBJECTIVES: To describe the expression of a potential new tumor marker, human glandular kallikrein 2 (hK2), in primary adenocarcinoma and lymph node metastases that may be useful as an adjunct to prostate-specific antigen (PSA) in the diagnosis and monitoring of prostate cancer. METHODS: We evaluated 151 radical prostatectomy specimens removed at Mayo Clinic with node-positive adenocarcinoma to compare cytoplasmic expression of hK2, pro-hK2, and PSA in benign tissue, prostate adenocarcinoma, and lymph node metastases. Monoclonal antibodies for mature hK2 (hK2-G586), pro-hK2 (pro-hK2-G464), and PSA (PSA-773) were used. A polyclonal antibody for PSA was also used. Immunoreactivity in each case was tested to determine whether cancer recurrence could be predicted. RESULTS: Intense epithelial cytoplasmic immunoreactivity was observed in every case for hK2-G586, pro-hK2-G464, PSA-773, and polyclonal PSA (100% of cases, respectively). The intensity and extent of hK2 expression was greater in lymph node metastases than in primary cancer; furthermore, the expression in primary cancer was greater than in benign epithelium. Pro-hK2 was expressed in a greater percentage of cells in primary cancer than in benign tissue; furthermore, pro-hK2 was expressed to a greater extent in primary cancer than in lymph node metastases. In marked contrast to mature hK2, monoclonal PSA immunoreactivity was expressed to a higher extent in primary cancer than in lymph node metastases. Polyclonal PSA showed an incremental increase in expression from benign tissue to primary cancer and a further increase in expression in lymph node metastases. CONCLUSIONS: hK2 was expressed in every cancer, and the expression incrementally increased from benign epithelium to primary cancer and lymph node metastases. Pro-hK2 was expressed to the greatest extent in primary cancer. Monoclonal PSA displayed inverse immunoreactivity compared with hK2. Polyclonal PSA showed incremental increases, suggesting that both hK2 and PSA were being detected. Tissue expression of hK2 appears to be regulated independently of PSA in benign epithelium, adenocarcinoma, and lymph node metastases.

Adenocarcinoma↗
PubMed1999

Does transurethral microwave thermotherapy have a different effect on prostate cancer than on benign or hyperplastic tissue?

OBJECTIVES: Transurethral microwave thermotherapy is useful for the treatment of benign prostatic hyperplasia, but its effect on cancer is not documented. We analyzed the pathologic changes occurring after microwave thermotherapy in whole mount radical prostatectomy specimens from patients with cancer. METHODS: Nine patients scheduled for radical prostatectomy for clinically localized prostate cancer were treated with transurethral microwave thermotherapy (Urologix Targis System). Patients ranged in age from 64 to 72 years (mean 68). Seven patients underwent prostatectomy 4 to 90 hours after thermotherapy, and 2 other patients underwent prostatectomy 12 months after thermotherapy. Whole mount totally embedded prostates were mapped for necrosis and cancer, and the volume of each was measured by the grid method. RESULTS: Pathologic stages were T2a (n = 4), T2b (n = 4), and T3b (n = 1). The prostates from patients who underwent radical prostatectomy within 4 to 90 hours of thermotherapy had a mean prostate weight of 47.4 g (range 19.5 to 70.3). Each consistently showed hemorrhagic necrosis and tissue devitalization without significant inflammation. Necrosis involved contiguous areas of benign epithelium, stroma, and cancer without skip areas. The mean volume of necrosis was 8.8 cc (range 1.4 to 17.8), and the mean percentage of the prostate involved by necrosis was 22% (range 3% to 39%). The necrosis was symmetric around the urethra in 6 of 7 cases. Urethral dilation was observed in 3 patients, and the mean maximum radial distance of necrotic tissue was 1.4 cm (range 0.6 to 1.8). Necrotic change was noted in 80% to 100% of the volume of cancer in 4 cases, 40% to 60% in 2 cases, and 5% in 1 case. The prostates from the 2 patients who underwent radical prostatectomy 12 months after thermotherapy had a mean weight of 88 g (55 and 121 g, respectively). Each showed periurethral fibrosis, nonspecific chronic inflammation, and squamous metaplasia of the urothelium. The mean volume of necrosis remaining was 0.2 cc. The mean percentage of the prostate involved by necrosis 1 year after thermotherapy was less than 1%. There was some reabsorption of dead tissue. The mean maximum radial distance of the necrotic tissue was 0.4 cm (0.2 and 0.7 cm, respectively). The prostatic urethra had viable and partially denuded urothelium in all cases. CONCLUSIONS: Microwave thermotherapy is clinically useful for ablation of benign prostate and cancer contiguous to the urethra, resulting in hemorrhagic necrosis with minimal damage to the urethra. There was no apparent differential morphologic sensitivity of benign prostatic tissue, hyperplastic tissue, or cancer to thermotherapy.

Aged↗
PubMed1999

Role of microvessel density in predicting recurrence in pathologic Stage T3 prostatic adenocarcinoma.

OBJECTIVES: Extraprostatic extension of prostatic adenocarcinoma (pathologic Stage T3) increases the risk of recurrence after radical prostatectomy compared with organ-confined prostate cancer. Use of microvessel density in predicting cancer recurrence in Stage pT3 cancer is poorly understood. We evaluated known predictors of recurrence, including Gleason grade, preoperative serum prostate-specific antigen (PSA), DNA ploidy, seminal vesicle involvement, and surgical margin status in comparison with optimized microvessel density (OMVD) and area-weighted microvessel density (AWMVD) in patients with Stage pT3 prostate cancer. METHODS: Between 1987 and 1989, 290 previously untreated patients underwent radical prostatectomy and were found to have pathologic Stage T3 adenocarcinoma. No patient received adjuvant therapy. Embedded prostatectomy specimens from 211 patients with sufficient tissue for immunohistochemical staining with factor VIII-related antigen were studied by computer-assisted digital image analysis for OMVD and AWMVD. The correlation of Gleason grade, preoperative PSA, DNA ploidy, seminal vesicle involvement, surgical margin positivity, OMVD, and AWMVD with clinical or biochemical failure was assessed using the Cox proportional hazards model. Biochemical failure was defined as a postoperative increase in PSA greater than 0.2 ng/mL, and clinical failure was defined as a positive biopsy or metastasis on bone scan. RESULTS: The mean follow-up +/- SD for all patients was 7.1 +/- 1.8 years, with 43 deaths (9 due to prostate cancer) and 124 cases of clinical and/or biochemical recurrence. The mean OMVD was 65.0 +/- 17.3, and the mean AWMVD was 8.2 +/- 5.3. OMVD and AWMVD were not predictors of cancer recurrence or significantly associated with DNA ploidy or preoperative PSA. AWMVD was associated with Gleason grade (P = 0.003). The estimated relative risk (adjusted for other cancer variables) of clinical and biochemical recurrence associated with a change in OMVD from the 25th percentile (53.5) to the 75th percentile (75.4) was 1.14 (95% confidence interval 0.92 to 1.42). The estimated relative risk (adjusted) of clinical and biochemical recurrence associated with a change in AWMVD from the 25th percentile (4.8) to the 75th percentile (10.4) was 1.17 (95% confidence interval 0.97 to 1.42). Gleason grade, preoperative PSA, DNA ploidy, and seminal vesicle involvement were predictors of clinical and/or biochemical recurrence in univariate and multivariate analyses. CONCLUSIONS: Microvessel density, assessed by OMVD and AWMVD, did not predict recurrence in patients with pathologic Stage T3 adenocarcinoma of the prostate (TNM Stage T3N0M0). DNA ploidy, Gleason grade, preoperative PSA, and seminal vesicle involvement remained the best predictors of clinical and/or biochemical recurrence in this group of patients.

Adenocarcinoma↗
PubMed1999

Prostate biopsy interpretation. Current concepts, 1999.

Needle biopsy of the prostate has a pivotal role in the diagnosis of prostate cancer and the prediction of outcome. Strategies for sampling the prostate are being refined, which will increase the diagnostic yield. In combination with other clinical factors, the pathologic findings obtained from the biopsy specimen provide enhanced predictive accuracy for stage and individual outcome.

Atrophy↗
PubMed1999

Treatment changes in prostatic hyperplasia and cancer, including androgen deprivation therapy and radiotherapy.

Substantial and characteristic changes occur in the microscopic appearance and immunophenotype of the hyperplastic prostate and adenocarcinoma following androgen deprivation therapy and radiotherapy. These changes are rarely seen in untreated cancer, and in the authors' opinion, the combinations of features following therapy are sufficiently distinctive to warrant recognition. Pathologists must be aware of these distinct changes because of the reliance placed on nuclear and nucleolar size in the identification of prostate cancer, particularly in small specimens and lymph node metastases.

5-alpha Reductase Inhibitors↗
PubMed1999

Diagnosis and grading of bladder cancer and associated lesions.

Standardized classification and grading of urothelial carcinoma has now been achieved internationally. Uniformity of pathologic reporting should improve the comparability of different studies and therapies and provide more accurate information to urologists in managing patients.

Carcinoma in Situ↗
PubMed1999

Diagnosis and classification of renal cell carcinoma.

Although substantial agreement exists in most aspects of diagnosis and staging of renal cell carcinoma, further work is needed to resolve unsettled issues regarding precursor lesions, grading, and the prediction of outcome for individual patients.

Carcinoma, Renal Cell↗
PubMed1999

Small cell carcinoma of urinary bladder is differentiated from urothelial carcinoma by chromogranin expression, absence of CD44 variant 6 expression, a unique pattern of cytokeratin expression, and more intense gamma-enolase expression.

AIMS: Small cell (neuroendocrine) carcinoma of the urinary bladder is clinically more aggressive than urothelial (transitional cell) carcinoma. We have investigated the immunohistochemical markers most useful in diagnosing small cell carcinoma in bladder. METHODS AND RESULTS: We evaluated the expression of chromogranin A, CD44 variant 6 (CD44v6), cytokeratin (CAM 5.2), gamma-enolase, synaptophysin, and CD45 in 46 small cell carcinomas of the bladder. Small cell and urothelial carcinoma were mixed in 21 (46%) cases. The two immunohistochemical markers with best ability to discriminate between small cell and urothelial carcinoma were chromogranin A and CD44v6. Chromogranin A had 97% specificity for small cell carcinoma, staining 65% of cases with 2+/3+ mean intensity; only one case (5%) of urothelial carcinoma was weakly (1+/3+) positive. CD44v6 was 80% specific for urothelial carcinoma, with immunoreactivity in 60% of cases, compared with 7% of small cell carcinoma cases. In cases positive for CD44v6, the mean percentage of reactive urothelial carcinoma cells was 75% (range 10-100%), greater than the 12% of cells in three cases of small cell carcinoma (P = 0.31); further, the pattern of immunoreactivity was membranous vs. focal cytoplasmic, respectively. All small cell carcinomas stained with one of the three neuroendocrine markers tested; 76% of cases were reactive for synaptophysin and 93% for gamma-enolase, with specificities of 86% and 73% in comparison to urothelial carcinoma. gamma-enolase staining of small cell carcinoma was more intense (P = 0.01) than for urothelial carcinoma. Cytokeratin CAM 5.2 stained a mean 47% of cells in small cell carcinoma, always in a punctate perinuclear pattern, and 75% in urothelial carcinoma, in a membranous pattern. CONCLUSIONS: CD44v6, chromogranin A, and possibly gamma-enolase and cytokeratin (CAM 5.2) help differentiate small cell carcinoma from urothelial carcinoma.

Adult↗
PubMed1999

Natural history of urothelial dysplasia of the bladder.

Urothelial dysplasia is the putative precursor of urothelial carcinoma in situ (CIS) and invasive urothelial carcinoma of the urinary tract. Urothelial dysplasia is frequently identified in patients with urothelial CIS and cancer. However, very little is known about the clinical presentation and natural history of urothelial dysplasia in the absence of urothelial CIS or invasive cancer. The authors studied 36 patients with isolated urothelial dysplasia at the Mayo Clinic between 1969 and 1984. None of these patients had previous or concurrent urothelial CIS or invasive cancer, and none received treatment for dysplasia. The histopathologic features of urothelial dysplasia were examined, and long-term clinical follow-up was obtained. Progression was defined as the development of urothelial CIS or carcinoma. The male-to-female ratio was 2.6:1, and the mean patient age at the time of diagnosis was 60 years (range 25-79). Urothelial dysplasia has a predilection for the posterior wall. Eleven patients had urinary irritative symptoms, 10 had hematuria, 3 had both irritative symptoms and hematuria, and 12 were found to have dysplasia incidentally. The mean follow-up was 8.2 years (range 0.1-25.5). Seven (19%) of 36 patients developed biopsy-proven progression, including 4 with CIS and 3 with invasive cancer, and 1 of them died of bladder cancer. The intervals from diagnosis to progression ranged from 6 months to 8 years (mean 2.5 years). One of the remaining 29 patients had positive cytologic results 2.5 years after the initial diagnosis of dysplasia. The authors conclude that urothelial dysplasia is a significant risk for the development of CIS and invasive urothelial carcinoma, and patients with urothelial dysplasia should be followed up closely.

Adult↗
PubMed1999

Villous adenoma of the urinary tract: a report of 23 cases, including 8 with coexistent adenocarcinoma.

Villous adenoma originating in the urinary tract is uncommon. We present the first study of a large number of cases of villous adenoma of the urinary tract with clinical follow-up. Our series consisted of 15 patients with isolated villous adenoma and 8 patients with coexistent adenocarcinoma. The tumors occurred in elderly patients and had a predilection for the urachus, dome, and trigone of the urinary bladder. The typical clinical presentation was hematuria and irritative symptoms, and endoscopic examination usually identified a tumor growth. There was no gender predominance. Light microscopic examination showed morphologic similarity to colonic villous adenoma in all cases. Each tumor was composed of pointed or blunt finger-like processes lined by pseudostratified columnar epithelium. The epithelial cells displayed nuclear stratification, nuclear crowding, nuclear hyperchromasia, and occasional prominent nucleoli and mitotic figures. There was intense carcinoembryonic antigen immunoreactivity on the luminal surfaces (89%). Most cases (78%) contained cytoplasmic acid mucin, demonstrated by Alcian blue periodic acid-Schiff stain. Cytokeratin 20 was positive in all cases, cytokeratin 7 was positive in 56% of cases, and epithelial membrane antigen was positive in 22% of cases. Recurrence or invasive adenocarcinoma did not develop in any patient with isolated villous adenoma during a mean follow-up of 9.9 years. Lung metastasis developed in one patient with coexistent adenocarcinoma and multiple recurrences in another (mean follow-up, 3 years). We conclude that the prognosis is excellent in patients with isolated villous adenoma, and complete surgical resection is curative. Patients with coexistent adenocarcinoma may experience recurrence or distant metastasis, and more aggressive treatment may be indicated.

Adenocarcinoma↗