Biomedical subjects

J C Cheville

Publications and source records attributed to J C Cheville.

At least 37 records · Page 2Linked to original sources

PubMed2000

Radiotherapy for isolated serum prostate specific antigen elevation after prostatectomy for prostate cancer.

PURPOSE: Elevated serum prostate specific antigen (PSA) may be the initial and only indication of disease recurrence after prostatectomy for prostate cancer. External beam radiotherapy may be given in this setting in an attempt to eradicate the disease but therapeutic outcomes after this approach require further description. We describe the intermediate term outcome in a large group of patients treated with radiotherapy and identify pre-therapy factors associated with disease outcome. MATERIALS AND METHODS: We retrospectively studied a cohort of 166 consecutive patients treated with radiotherapy between July 1987 and May 1996. The Kaplan-Meier method was used to describe patient outcome for the overall study group, and statistical associations of pre-therapy variables with outcome were sought to identify predictive factors. RESULTS: At a median followup of 52 months 46% (95% confidence interval 38 to 55) of patients were expected to be free of biochemical relapse 5 years after radiotherapy. Multivariate analysis identified pathological classification (seminal vesicle invasion), tumor grade and preradiotherapy serum PSA as independent factors associated with biochemical relapse. Although in 1 of 6 patients a chronic complication was attributed to radiotherapy, it was often mild and self-limited in nature. CONCLUSIONS: In our current series approximately half of the patients treated with radiotherapy for an isolated elevation of serum PSA after prostatectomy were free of biochemical relapse at 5 years of followup. Radiotherapy may be given in this setting with modest long-term morbidity.

Adult↗

PubMed2000

The cell cycle inhibitors p21WAF1 and p27KIP1 are associated with survival in patients treated by salvage prostatectomy after radiation therapy.

We evaluated p27KIP1 and p21WAF1 expression in 52 patients treated by salvage radical prostatectomy and bilateral pelvic lymphadenectomy for biopsy-proven locally persistent or recurrent prostate cancer after external beam radiation therapy. We defined low and high expression based on the median value observed in our sample. Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p21 (< or =5%), compared with 94 and 100%, respectively, for those with high expression of p21 (>5%; P = 0.02 and 0.01, respectively). Five-year distant metastasis-free survival and cancer-specific survival were 71 and 82%, respectively, for patients with low expression of p27 (<50%), compared with 88 and 96%, respectively, for those with high expression of p27 (> or =50%; P = 0.06 and 0.01, respectively). These findings indicate that p21 and p27 expression levels are significant predictors of survival for patients selected for salvage prostatectomy for recurrent prostate cancer.

Aged↗

PubMed2000

A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma.

PURPOSE: We determine the relative sensitivities of cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS: A mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene) was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. A total of 280 urine specimens from 265 patients, including 150 with a history of urothelial carcinoma and 115 without a history of urothelial carcinoma, were analyzed. FISH analysis was performed without prior knowledge of clinical findings, that is biopsy, cystoscopy and cytology results. A positive result was defined as 5 or more urinary cells with gains of 2 or more chromosomes. RESULTS: A total of 75 biopsies showed urothelial carcinoma at FISH analysis among the 265 patients. The sensitivity of urine cytology for pTa (36 cases), pTis (18) and pT1-pT4 (15) tumors was 47%, 78% and 60%, respectively, for an overall sensitivity of 58%. The sensitivity of FISH for pTa (37 cases), pTis (17) and pT1-pT4 (19) tumors was 65%, 100% and 95%, respectively, for an overall sensitivity of 81%. FISH was significantly more sensitive than cytology for pTis (p = 0.046), pT1-pT4 (p = 0.025), grade 3 (p = 0.003) and all tumors (p = 0.001). The specificity of cytology and FISH among patients without cystoscopic evidence of urothelial carcinoma and no history of urothelial carcinoma was 98% and 96%, respectively (p = 0.564). CONCLUSIONS: The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.

Centromere↗

PubMed1999

Urothelial papilloma of the bladder. Clinical and biologic implications.

BACKGROUND: An international consensus has been reached regarding diagnostic criteria for papilloma of the urinary bladder. However, the incidences of recurrence and progression in patients with urothelial papilloma are uncertain. METHODS: The population for this study consisted of 52 patients who were diagnosed with urothelial papilloma of the bladder at the Mayo Clinic between 1914 and 1998. All histologic slides were reviewed and fulfilled the diagnostic criteria of urothelial papilloma from the 1998 World Health Organization/International Society of Urological Pathology classification system. No patients had previous or coexistent urothelial carcinoma, and none were treated after biopsy. RESULTS: The mean patient age at diagnosis was 57 years (range, 22-89 years). The male-to-female ratio was 1.9:1. The mean follow-up was 9.8 years (range, 0.1-58 years). Four patients developed recurrent papilloma (mean interval from diagnosis to recurrence, 3.3 years); 1 other patient developed papillary neoplasm of low malignant potential (Ta WHO Grade 1 papillary urothelial carcinoma) 6 years after the initial diagnosis of papilloma. None of these patients developed dysplasia, carcinoma in situ, or invasive urothelial carcinoma or died of bladder cancer. CONCLUSIONS: Patients with urothelial papilloma have a low incidence of recurrence and rarely, if ever, develop urothelial carcinoma.

Adult↗

PubMed1999

Dedifferentiation in the metastatic progression of prostate carcinoma.

BACKGROUND: Dedifferentiation is a distinctive feature of cancer progression. Detailed histologic analysis of primary prostate carcinoma and synchronous lymph node metastases may improve our understanding of the complex process of cancer progression and metastasis. METHODS: The authors studied 242 regional lymph node positive prostate carcinoma patients who underwent radical prostatectomy and bilateral lymphadenectomy between 1987 and 1992 at the Mayo Clinic. Patients ranged in age from 47-79 years (median, 66 years). The median follow-up was 6.1 years. Gleason scores of lymph node metastases and primary tumors were compared and correlated with systemic disease progression. Histologic dedifferentiation was defined as a higher Gleason grade in the lymph node metastases than in the primary tumor. Systemic disease progression was defined as the presence of distant metastases documented by biopsies, abdominal computed tomography, plain radiograph, or bone scan. RESULTS: The 5-year systemic progression free survival (PFS) rate was 90%. The Gleason score in the lymph node metastases was higher than in the primary tumor in 45% of patients, lower in 12% of patients, and matched exactly in 43% of patients. The 5-year PFS was significantly different between patients with histologic dedifferentiation (88% +/- 3) and those without dedifferentiation (94% +/- 2) (P = 0.04). Adjusting for the Gleason grade of the primary tumor and total lymph node tumor volume, the relative risk for disease progression associated with dedifferentiation was 1.8 (95% confidence interval, 0.7-4.7; P = 0.25). CONCLUSIONS: The findings of the current study demonstrate the morphologic heterogeneity of metastases from prostate carcinoma. There is a trend toward histologic dedifferentiation when prostate carcinoma metastasizes to regional lymph nodes. This dedifferentiation, although univariately significant, was not associated with disease progression when adjusted for lymph node tumor volume.

Aged↗

PubMed1999

Hemangioma of the urinary bladder.

BACKGROUND: Hemangioma of the urinary bladder is rare and the long term outcome of patients is unknown. METHODS: The authors evaluated the clinical and pathologic findings in 19 patients with a vesical hemangioma. All patients were treated at the Mayo Clinic between 1932-1998 and had histologic confirmation of the diagnosis. Hemangioma was classified into cavernous, capillary, or arteriovenous types based on conventional criteria from other sites. Clinical information was obtained from chart review. The mean follow-up of the patients was 6.9 years (range, 0.3-25 years). RESULTS: The mean patient age at the time of diagnosis was 58 years (range, 19-76 years) and the male-to-female ratio was 3.7:1. Patients typically presented with macroscopic hematuria and endoscopic findings usually were nonspecific. The diagnosis of hemangioma was suspected in 3 patients (16%) prior to biopsy. There was a predilection for the posterior and lateral walls and the tumor usually was small (range, 0.2-3 cm; median, 0.7 cm) and solitary. The histologic types of hemangioma were cavernous (15 cases), capillary (2 cases), and arteriovenous (2 cases). All patients were treated with biopsy with or without fulguration, except for one patient who was treated with a partial cystectomy. No patients developed a recurrence during a mean follow-up of 6.9 years. CONCLUSIONS: Patients with hemangioma of the urinary bladder have a favorable outcome. Biopsy and fulguration are effective for hemangioma of the bladder when the lesion is small.

Adult↗

PubMed1999

Neurofibroma of the urinary bladder.

BACKGROUND: Neurofibroma of the urinary bladder is rare. Only isolated case reports have appeared. Information regarding the long term follow-up of patients with neurofibroma is limited. METHODS: The authors studied 4 cases of neurofibroma of the bladder diagnosed at Mayo Clinic from 1965 through 1990. Immunostains for S-100 protein, neurofilament protein, epithelial membrane antigen (EMA), cytokeratin (CAM 5.2; AE 1/3), Type IV collagen, MIB-1, and p53 protein were performed in all cases, as was Alcian blue at pH 2.5. The mean follow-up was 9.6 years (range, 2-18 years). RESULTS: The mean age at diagnosis was 17 years (range, 7-28 years); the male-to-female ratio was 1:1. All four patients exhibited physical stigmata of neurofibromatosis type 1. Clinical presentations included hematuria (one patient), irritative symptoms (two patients), and pelvic mass (one patient). Long term urinary complications included bladder atony (two patients), neurogenic bladder (one patient), and recurrent urinary tract infection with hematuria (one patient). Subsequently, two patients underwent partial cystectomy and one a complete cystectomy. Involvement of the bladder was generalized in all four cases. Three tumors were transmural, showing a diffuse and plexiform pattern of growth; in the fourth case, a superficial biopsy showed only diffuse submucosal growth with conspicuous pseudo-Meissnerian corpuscle formation. An Alcian blue positive, variably collagenized matrix was present in all cases. Tumor cells displayed immunoreactivity for S-100 protein and Type IV collagen in all cases. Neurofilament protein positive axons were evident in three cases; all other immunostains were negative. The mean MIB-1 labeling index was 3.2% (range, 0.9-7.3%). No malignant transformation was observed during a mean follow-up of 9.6 years. CONCLUSIONS: Neurofibroma of the bladder presents early in life, is of the plexiform type with a diffuse component, and usually occurs in the setting of generalized neurofibromatosis type 1 rather than as isolated visceral neurofibromatosis. Malignant transformation did not occur in any of these 4 patients during a mean follow-up time of 9.6 years.

Adolescent↗

PubMed1999

Survival of patients with carcinoma in situ of the urinary bladder.

BACKGROUND: To the authors' knowledge, the long term follow-up of patients with carcinoma in situ of the urinary bladder is limited. METHODS: The authors studied 138 patients diagnosed with urothelial carcinoma in situ of the bladder at the Mayo Clinic between 1972-1979. All the histologic slides were reviewed and fulfilled the diagnostic criteria for carcinoma in situ according to the newly proposed World Health Organization and International Society of Urologic Pathology classification system. None of these patients had previous or coexisting invasive urothelial carcinoma at the time of diagnosis. Cox proportional hazards models were used to determine the prognostic significance of numerous clinical and pathologic findings using progression free, cancer specific, and all-cause survival as the endpoints for analysis. Progression was defined as the development of invasive carcinoma, distant metastases, or death from bladder carcinoma. RESULTS: The patients ages at the time of diagnosis ranged from 32-90 years (mean, 65.6 years). The male to female ratio was 7:1. Carcinoma in situ usually was multifocal (50%) with a predilection for the trigone, lateral wall, and dome. The mean follow-up after surgery was 11.0 years (range, 0.7-25 years). Actuarial progression free, cancer specific, and all-cause survival rates were 63%, 79%, and 55%, respectively, at 10 years, and 59%, 74%, and 40%, respectively, at 15 years. The mean interval from the time of diagnosis to cancer progression was 5 years. Patient age at diagnosis was significant in predicting progression free (P = 0.01) and all-cause survival (P = 0.002). Cystectomy performed within 3 months after the initial diagnosis was associated with improved all-cause survival (P = 0.03). After controlling for age, there was no difference in survival between patients who received immediate cystectomy and those did not (P = 0.16). CONCLUSIONS: Patients with carcinoma in situ of the bladder are at significant risk of cancer progression and death from bladder carcinoma. Cystectomy does not appear to offer a significant survival advantage in patients with carcinoma in situ of the bladder after adjusting for age.

Adult↗

PubMed1999

p53 protein overexpression is associated with increased cell proliferation in patients with locally recurrent prostate carcinoma after radiation therapy.

BACKGROUND: The biologic changes in recurrent prostate carcinoma following radiation therapy are not fully understood. The authors sought to determine the level of p53 protein overexpression and its association with cellular proliferation (Ki-67 labeling index), glutathione S-transferase-pi (GST-pi) expression, and other clinical pathologic findings in patients with locally persistent prostate carcinoma after radiation therapy. METHODS: The authors investigated p53 nuclear accumulation, cellular proliferation activity (Ki-67 labeling index by digital image analysis), and GST-pi expression in 55 patients with persistent or recurrent prostate carcinoma after radiation therapy. All patients underwent salvage radical prostatectomy and bilateral pelvic lymphadenectomy following irradiation failure. The interval from radiation therapy to cancer recurrence ranged from 6 months to 17 years (mean, 3.8 years). Age at surgery ranged from 51 to 78 years (mean, 65 years). Mean follow-up after surgery was 5.7 years (range, 1-13 years). RESULTS: p53 protein overexpression was associated with increased cell proliferation (Spearman rank correlation coefficient = 0.29, P = 0.03). A substantial proportion (62%) of recurrent cancer also showed GST-pi immunoreactivity. No apparent correlation was observed between p53 protein overexpression, cellular proliferation (Ki-67 labeling index), or GST-pi expression and Gleason score, pathologic stage, DNA ploidy, or patient outcome. There was an inverse correlation between GST-pi expression and Gleason score (P = 0.06). The majority of prostate carcinomas (95%) were proliferative (mean Ki-67 labeling index, 7.0; range, 0-20), whereas concurrent prostatic intraepithelial neoplasia (PIN) had a lower Ki-67 labeling index (mean, 3.1; range, 0-11.5). Nineteen of 28 (68%) concurrent PIN demonstrated p53 immunoreactivity. A trend toward adverse clinical outcome was observed in patients with a higher Ki-67 labeling index in recurrent cancer. CONCLUSIONS: In this study cohort selected for salvage prostatectomy, recurrent cancers were biologically aggressive following radiation therapy. Whether this represents selective persistence and regrowth of prognostically unfavorable tumor clonogens or stepwise clonogenic progression is uncertain. Further investigation is needed to elucidate the correlation between p53 overexpression and the presence of other biologic changes after radiation therapy.

Aged↗

PubMed1999

p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers.

p27kip1 (p27) is a member of the universal cyclin-dependent kinase inhibitor (CDKI) family. p27 expression is regulated by cell contact inhibition and by specific growth factors, such as transforming growth factor (TGF)-beta. Since the cloning of the p27 gene in 1994, a host of other functions have been associated with this cell cycle protein. In addition to its role as a CDKI, p27 is a putative tumor suppressor gene, regulator of drug resistance in solid tumors, and promoter of apoptosis; acts as a safeguard against inflammatory injury; and has a role in cell differentiation. The level of p27 protein expression decreases during tumor development and progression in some epithelial, lymphoid, and endocrine tissues. This decrease occurs mainly at the post-translational level with protein degradation by the ubiquitin-proteasome pathway. A large number of studies have characterized p27 as an independent prognostic factor in various human cancers, including breast, colon, and prostate adenocarcinomas. Here we review the role of p27 in the regulation of the cell cycle and other cell functions and as a diagnostic and prognostic marker in human neoplasms. We also review studies indicating the increasingly important roles of p27, other CDKIs, and cyclins in endocrine cell hyperplasia and tumor development.

Cell Cycle↗

PubMed1999

Classification and pathology of testicular germ cell and sex cord-stromal tumors.

Germ cell tumors of the testis are the most frequent testicular neoplasms, with seminoma predominating. The pathologist must be able to discriminate between seminoma and nonseminomatous germ cell tumors as well as sex cord-stromal tumors and metastatic lesions. Appropriate therapy and accurate prognostic information are dependent on the proper classification of testicular neoplasia. Characteristic histologic features, serum markers, and immunohistochemistry are helpful in this regard. Sex cord-stromal tumors comprise a small minority of testicular neoplasms. It remains critically important not to confuse these neoplasms with testicular germ cell or metastatic tumors, and, again, recognition of the characteristic histologic features, immunohistochemical findings, and clinical information is diagnostic. The urologist can provide the pathologist with key clinical information in the attempt to make a correct diagnosis.

Carcinoma, Embryonal↗

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

Prevalence and distribution of prostatic intraepithelial neoplasia in salvage radical prostatectomy specimens after radiation therapy.

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer. The effect of radiation therapy (RT) on the prevalence of PIN is uncertain. We studied 86 patients who underwent salvage radical prostatectomy after irradiation failure at the Mayo Clinic. The prevalence, volume, multicentricity, spatial proximity to cancer, and architectural patterns of PIN were evaluated. High-grade PIN was identified in 53 (62%) of 86 prostatectomy specimens. Multiple architectural patterns were usually observed, including tufting in 87%, micropapillary in 66%, cribriform in 38%, and flat in 17%. The mean volume of PIN was 0.12 cm3 (range, 0.05-1.20 cm3). PIN was usually multicentric (70%), with a mean number of PIN foci of 2.5 (range, 1-10). Ninety-four percent of PIN foci were located within 2 mm of invasive cancer. There was no correlation between PIN and pathologic stage, surgical margin, tumor size, DNA ploidy, post-RT Gleason score, time interval from RT to biopsy-proven recurrence, postoperative prostate-specific antigen level, distant metastasis-free survival, or cancer-specific survival. Our examination of salvage radical prostatectomy specimens indicated that the prevalence and extent of PIN appeared to be reduced after RT compared to published studies of prostatectomies without prior RT.

Aged↗

PubMed1999

Diagnosis of prostate cancer in needle biopsies after radiation therapy.

Interpretation of postirradiation needle biopsies is a major diagnostic challenge for the pathologist because of substantial radiation-induced changes in benign and malignant prostatic tissue. Reports that have systematically evaluated the histopathologic findings in postirradiation needle biopsies are limited. In this study, we evaluated 46 histologic features in 29 postirradiation needle biopsy specimens from 29 patients. All patients had recurrent cancer on needle biopsies after external beam radiation, and all subsequently underwent salvage radical prostatectomy and bilateral pelvic lymphadenectomy. Patient age ranged from 57 to 78 years (mean, 61 years). The interval from radiation therapy to biopsy ranged from 1.0 to 17 years (mean, 3.9 years). Histologic features that were helpful in the diagnosis of cancer after radiation therapy included infiltrative growth, perineural invasion, intraluminal crystalloids, blue mucin secretions, the absence of corpora amylacea, and the presence of coexistent high-grade prostatic intraepithelial neoplasia. Benign glands usually showed nuclear enlargement (86%) and prominent nucleoli (50%), and therefore, these cytologic features alone were not reliable for the diagnosis of cancer after irradiation. Postirradiation needle biopsies underestimated the prostatectomy Gleason grade in 35% of cases and overestimated it in 14% of cases; these results were similar to published reports from patients not receiving radiation therapy. There was a major discrepancy in degree of radiation effect between radical prostatectomy and biopsies. Moderate or severe radiation effect on cancer was present in 48% of needle biopsy specimens, whereas 94% of radical prostatectomy specimens had no or minimal radiation effect on cancer when the areas with the least amount of radiation effect were chosen for quantification. These findings indicate that quantification of radiation effect in needle biopsy specimens was inaccurate and potentially misleading. Conversely, Gleason grade in postirradiation needle biopsy specimens appeared to provide useful predictive information and should be reported.

Adenocarcinoma↗

PubMed1999

MAGE-1 and MAGE-3 tumor rejection antigens in human germ cell tumors.

The MAGE-1 and MAGE-3 genes are members of the melanoma antigen-encoding gene family. These genes encode for HLA-restricted tumor-associated rejection antigens recognized by cytotoxic T lymphocytes. MAGE-1 and MAGE-3 gene expression has been identified in a number of human malignancies, and MAGE-1 and MAGE-3 antigenic peptides are potential targets for tumor-specific immunotherapy. The only normal tissues known to express these genes are testicular germ cells and placental tissue. The objective of this study was to examine MAGE-1 and MAGE-3 antigens immunohistochemically in testicular germ cell tumors, including seminoma, a germ cell tumor frequently associated with a lymphoid infiltrate. Forty-three germ cell tumors (24 seminomas, six embryonal carcinomas and 13 mixed germ cell tumors), and 10 Leydig cell tumors were selected for study, and standard immunohistochemical techniques were used on formalin-fixed paraffin-embedded tissues using mouse monoclonal antibodies to MAGE-1 (clone M454) and MAGE-3 (clone 57B) antigens. MAGE-1 antigen was identified in 16.6% of seminomas. No embryonal carcinomas, yolk sac tumors, or teratomas contained MAGE-1 protein. MAGE-3 antigen was identified in 41.8% of seminomas, and this protein was not identified in embryonal carcinomas, yolk sac tumors, or teratoma. Spermatogonia and primary spermatocytes contained MAGE-1 and MAGE-3 antigen, and more mature forms, including spermatids, were weakly positive to negative. Leydig cell tumors were negative for MAGE-1 and MAGE-3. In seminoma, the presence of MAGE-1 and MAGE-3 antigens did not correlate with tumor size, tumor stage, the presence of a lymphoid infiltrate, or patient outcome. The low frequency of MAGE-specific HLA alleles in the population, the loss of the HLA class I antigens in neoplastic germ cells, and the finding that the majority of seminomas and all non-seminomatous germ cell tumors lacked MAGE-1 and MAGE-3 antigenic peptides indicate that immunotherapy directed towards MAGE-1 and MAGE-3 antigen is not a likely treatment option for seminoma and nonseminomatous germ cell tumors. The significance of MAGE-1 and MAGE-3 proteins in normal spermatogonia and primary spermatocytes will require additional study.

Adult↗

PubMed1998

Transitional cell carcinoma of the prostate: clinicopathologic study of 50 cases.

BACKGROUND: This study was performed to identify clinical and histologic features most significant in predicting outcome in patients with transitional cell carcinoma (TCC) of the prostate without invasive bladder carcinoma. METHODS: The histologic and clinical material from 50 patients with prostatic TCC without invasive bladder carcinoma were studied. The tumors were divided into the following locoregional categories: 1) TCC in situ (CIS) of the prostatic urethra; 2) CIS of the prostatic ducts and acini; 3) TCC with stromal invasion; 4) TCC with extraprostatic extension and/or seminal vesicle involvement; and 5) lymph node metastases. The Kaplan-Meier method was used to generate survival distributions for the locoregional categories, and comparison of survival curves was accomplished with the log rank test. RESULTS: The 5-year disease specific survival rate was 52%. The 5-year disease specific survival rates for the locoregional categories were as follows: CIS of the prostatic urethra and prostatic ducts and acini (n = 19), 100%; TCC with stromal invasion (n = 21), 45%; TCC with extraprostatic extension and seminal vesicle involvement (n = 3), 0%; and lymph node metastases (n = 7), 30%. There was a significant difference in disease specific survival when patients with CIS were compared with patients with stromal invasion, extraprostatic extension and seminal vesicle involvement, and lymph node metastases (P = 0.0001). CONCLUSIONS: This study demonstrates that patients with prostatic TCC involving prostatic stroma, extraprostatic tissues, seminal vesicles, and lymph nodes have a significantly poorer 5-year disease specific survival than patients with CIS.

Aged↗

PubMed1998

Atypical adenomatous hyperplasia of the prostate: a premalignant lesion?

To better understand genetic alterations in atypical adenomatous hyperplasia (AAH) of the prostate, we examined the prevalence of allelic imbalance at 5 microsatellite polymorphic markers on chromosomes 7q31-35, 8p12-21, 8p22, 8q22.2, and 18q12.2 from 15 patients with AAH. DNA samples were obtained from formalin-fixed paraffin-embedded sections using tissue microdissection. We found allelic imbalance in 7 of 15 (47%) cases of AAH. Genetic changes that commonly occur in early prostatic carcinogenesis and prostate carcinoma are found in AAH. Current data provide evidence of a genetic link between some cases of AAH and carcinoma.

Adenocarcinoma↗

PubMed1998

Leydig cell tumor of the testis: a clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors.

Leydig cell tumors of the testis are rare and account for a small proportion of testicular neoplasms. The objective of this study was to identify clinical and morphologic features predictive of metastasis in a large series of Leydig cell tumors, and to determine whether ploidy or proliferative activity were predictive of malignancy. Thirty cases of Leydig cell tumor of the testis (23 tumors that had not metastasized and 7 that had metastasized) were studied. Clinical history and follow-up were collected in all cases. The morphologic features examined included tumor size, mitotic index (mitotic figures/10 high-power fields), necrosis, angiolymphatic invasion, cell type, tumor-testicle interface, presence of extension beyond the testicular parenchyma, and presence of lipochrome and Reinke crystals. Most patients (93%) had a testicular mass. Patients with Leydig cell tumors that metastasized were diagnosed at a mean age of 62 years (range, 39-70 years) compared with 48 years (range, 9-79 years) in patients with nonmetastasizing tumors (p = 0.25). Leydig cell tumors that metastasized were significantly larger than nonmetastasizing tumors (mean, 4.7 versus 2.6 cm, respectively; p = 0.008), and had a significantly higher mitotic index (mean, 13.9 versus 1.9, respectively; p < 0.0001). Metastasizing Leydig cell tumors were significantly associated with atypical mitotic figures (p < 0.0001), nuclear variation (p = 0.0025), necrosis (p < 0.0001), angiolymphatic invasion (p = 0.009), infiltrative margins (p < 0.0001), high grade (p = 0.0004), and invasion into rete testis, epididymis, or tunica (p = 0.001) when compared with nonmetastasizing tumors. There was no significant difference between metastasizing and nonmetastasizing tumors in regard to cell type, lipochrome content, presence of Reinke crystals, or nuclear inclusions. All Leydig cell tumors that metastasized and 7 of 18 (38.9%) nonmetastasizing tumors were DNA aneuploid by static image analysis (p = 0.02). Metastasizing Leydig cell tumors had a significantly higher mean MIB-1 activity of 18.6% (range, 5.8-33.6) compared with 1.2% (range, 0.04-8.2) in nonmetastasizing tumors (p = 0.001). In this study, the presence of cytologic atypia, necrosis, angiolymphatic invasion, increased mitotic activity, atypical mitotic figures, infiltrative margins, extension beyond the testicular parenchyma, DNA aneuploidy, and increased MIB-1 activity were significantly associated with metastatic behavior in Leydig cell tumors.

Adolescent↗