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Biomedical subjects

John N Eble

Publications and source records attributed to John N Eble.

At least 19 recordsLinked to original sources
PubMed2005

Clonal origin of lymph node metastases in bladder carcinoma.

BACKGROUND: Evidence of genetic heterogeneity within urothelial carcinomas of the bladder has raised questions about the clonal origin of urothelial carcinoma and its metastases. High-grade urothelial carcinoma of the bladder frequently metastasizes to multiple regional lymph nodes in the pelvis. Whether or not these multiple lymph node metastases originate from the same tumor clone is uncertain. Molecular analysis of microsatellite alterations and X-chromosome inactivation status of distinct tumor cell populations from the same patient may further our understanding of the genetic basis of carcinoma progression and metastasis. METHODS: The authors examined 24 patients who underwent radical cystectomy for urothelial carcinoma. All patients had multiple (from two to four) lymph node metastases. Genomic DNA samples were prepared from formalin fixed, paraffin embedded tissue sections using laser-assisted microdissection. Loss of heterozygosity (LOH) assays for 3 microsatellite polymorphic markers on chromosome 9p21 (D9S171, region of putative tumor suppressor gene p16), 9q32 (D9S177, putative tumor suppressor gene involved in urothelial carcinoma tumorigenesis), and 17p13 (TP53, the p53 locus) were performed. In addition, X-chromosome inactivation analysis was performed in primary tumors and metastases from 10 female patients. RESULTS: In total, 79 tumors were analyzed. The overall frequency of allelic loss was 67% (16 of 24 tumors) in the primary urothelial carcinomas and 79% (19 of 24 tumors) in the metastatic carcinomas. The primary urothelial carcinoma showed LOH at the D9S171, D9S177, and TP53 loci in 39% (9 of 23 tumors), 30% (6 of 20 tumors), and 30% (7 of 23 tumors) of informative samples, respectively. LOH in > or = 1 lymph node metastases was seen at the D9S171, D9S177, and TP53 loci in 35% (8 of 23 tumors), 45% (9 of 20 tumors), and 48% (11 of 23 tumors) of informative samples, respectively. Eleven tumors demonstrated identical allelic loss patterns at all DNA loci both in the primary carcinoma and in all corresponding lymph node metastases. Three tumors showed allelic loss in the metastatic carcinoma but not in its matched primary carcinoma. Six tumors demonstrated a different LOH pattern in each of its lymph node metastases. Clonality analysis showed the same pattern of nonrandom X-chromosome inactivation both in the primary urothelial carcinoma and in all of the lymph node metastases in five of nine informative tumors studied. Four tumors showed a random pattern of X-chromosome inactivation in both the primary carcinoma and in the metastases. CONCLUSIONS: LOH and X-chromosome inactivation assays showed that multiple lymph node metastases and matched primary urothelial carcinomas of the bladder had the same clonal origin, suggesting that the capability for metastasis often arises in only a single clonal population in the primary tumor. The variable LOH patterns observed in some of the tumors likely reflect genetic divergence during the clonal evolution of urothelial carcinoma.

Adult↗
PubMed2005

Molecular genetic evidence for the independent origin of multifocal papillary tumors in patients with papillary renal cell carcinomas.

PURPOSE: In patients with papillary renal cell carcinoma, it is not uncommon to find two or more anatomically distinct and histologically similar tumors at radical nephrectomy. Whether these multiple papillary lesions result from intrarenal metastasis or arise independently is unknown. Previous studies have shown that multifocal clear cell renal cell carcinomas express identical allelic loss and shift patterns in the different tumors within the same kidney, consistent with a clonal origin. However, similar clonality assays for multifocal papillary renal cell neoplasia have not been done. Molecular analysis of microsatellite and chromosome alterations and X-chromosome inactivation status in separate tumors in the same patient can be used to study the genetic relationships among the coexisting multiple tumors. EXPERIMENTAL DESIGN: We examined specimens from 21 patients who underwent radical nephrectomy for renal cell carcinoma. All patients had multiple separate papillary lesions (ranging from 2 to 5). Eighteen patients had multiple papillary renal cell carcinomas. Seven had one or more papillary renal cell carcinomas with coexisting papillary adenomas. Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays were done for six microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p14 (D3S1285), 7q31 (D7S522), 9p21 (D9S171), 16q23 (D16S507), 17q21 (D17S1795), and 17p13 (TP53). X-chromosome inactivation analyses were done on the papillary kidney tumors from three female patients. Fluorescence in situ hybridization analysis was done on the tumors of selected patients showing allelic loss at loci on chromosome 7 and/or chromosome 17. RESULTS: Twenty of 21 (95%) cases showed allelic loss in one or more of the papillary lesions in at least one of the six polymorphic markers analyzed. A concordant allelic loss pattern between each coexisting kidney tumor was seen in only 1 of 21 (5%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the coexisting multiple papillary lesions was seen in two of three female patients. A discordant pattern of X-chromosome inactivation was seen in the tumors of the other female patient. Fluorescence in situ hybridization showed that the majority of tumors analyzed had gains of chromosomes 7 and 17. Two patients had one tumor with chromosomal gain and another separate tumor that did not. CONCLUSION: Our data suggest that, unlike multifocal clear cell renal cell carcinomas, the multiple tumors in patients with papillary renal cell carcinoma arise independently. Thus, intrarenal metastasis does not seem to play an important role in the spread of papillary renal cell carcinoma, a finding that has surgical, therapeutic, and prognostic implications.

Adult↗
PubMed2005

Clonal divergence and genetic heterogeneity in clear cell renal cell carcinomas with sarcomatoid transformation.

BACKGROUND: Approximately 5% of clear cell renal cell carcinomas contain components with sarcomatoid differentiation. It has been suggested that the sarcomatoid elements arise from the clear cell tumors as a consequence of clonal expansions of neoplastic cells with progressively more genetic alterations. Analysis of the pattern of allelic loss and X-chromosome inactivation in both the clear cell and sarcomatoid components of the same tumor allows assessment of the genetic relationship of these tumor elements. METHODS: The authors of the current study examined the pattern of allelic loss in clear cell and sarcomatoid components of renal cell carcinomas from 22 patients who had tumors with both components. DNA samples were prepared from formalin-fixed, paraffin-embedded renal tissue sections using laser-capture microdissection. Five microsatellite polymorphic markers for putative tumor suppressor genes on 5 different chromosomes were analyzed. These included D3S1300 (3p14), D7S522 (7q31), D8S261 (8p21), D9S171 (9p21), and TP53 (17p13). In addition, X-chromosome inactivation analysis was performed in 14 tumors from female patients. RESULTS: The clear cell components showed loss of heterozygosity (LOH) at the D3S1300, D7S522, D8S261, D9S171, and TP53 loci in 18% (4/22), 18% (4/22), 50% (10/20), 15% (3/20), and 20% (4/20) of informative cases, respectively. LOH in the sarcomatoid components was seen at the D3S1300, D7S522, D8S261, D9S171, and TP53 loci in 18% (4/22), 41% (9/22), 70% (14/20), 35% (7/20), and 20% (4/20) of informative cases, respectively. Six cases demonstrated an LOH pattern in the clear cell component that was not seen in the sarcomatoid component. Different patterns of allelic loss were seen in the clear cell and sarcomatoid components in 15 cases. Clonality analysis showed the same pattern of nonrandom X-chromosome inactivation in both clear cell and sarcomatoid components in 13 of the 14 cases studied. One case showed a random pattern of X-chromosome inactivation. CONCLUSION: X-chromosome inactivation analysis data suggest that both clear cell and sarcomatoid components of renal cell carcinomas are derived from the same progenitor cell. Different patterns of allelic loss in multiple chromosomal regions were observed in clear cell and sarcomatoid components from the same patient. This genetic heterogeneity indicates genetic divergence during the clonal evolution of renal cell carcinoma.

Adult↗
PubMed2005

Molecular evidence supporting field effect in urothelial carcinogenesis.

PURPOSE: Human urothelial carcinoma is thought to arise from a field change that affects the entire urothelium. Multifocality of urothelial carcinoma is a common finding at endoscopy and surgery. Whether these coexisting tumors arise independently or are derived from the same tumor clone is uncertain. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in the cells from each coexisting tumor may further our understanding of urothelial carcinogenesis. EXPERIMENTAL DESIGN: We examined 58 tumors from 21 patients who underwent surgical excision for urothelial carcinoma. All patients had multiple separate foci of urothelial carcinoma (two to four) within the urinary tract. Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity (LOH) assays for three microsatellite polymorphic markers on chromosome 9p21 (IFNA and D9S171), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p53 tumor suppressor gene locus, were done. X-chromosome inactivation analysis was done on the urothelial tumors from 11 female patients. RESULTS: Seventeen of 21 (81%) cases showed allelic loss in one or more of the urothelial tumors in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between each coexisting urothelial tumor were seen in only 3 of 21 (14%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting urothelial tumors was seen in only 3 of 11 female patients; of these 3 cases, only one displayed an identical allelic loss pattern in all of the tumors on LOH analysis. CONCLUSION: LOH and X-chromosome inactivation assays show that the coexisting tumors in many cases of multifocal urothelial carcinoma have a unique clonal origin and arise from independently transformed progenitor urothelial cells, supporting the "field effect" theory for urothelial carcinogenesis.

Adult↗
PubMed2005

Application of molecular diagnostic techniques to renal epithelial neoplasms.

The application of molecular and cytogenetic techniques to the study of renal neoplasia has resulted in improved understanding of the biologic mechanisms that are responsible for tumor development and progression. It also revealed that several different and specific genetic events are responsible for tumorigenesis in the various categories and subcategories of renal tumors. The ultimate goal of research on the molecular pathology of renal neoplasms is a complete understanding of the genetics of these tumors, which will, in turn, aid in making the correct diagnosis, accurately assessing prognosis, and selecting appropriate and targeted therapeutic options.

Adenocarcinoma, Clear Cell↗
PubMed2005

Thyroid transcription factor 1 expression in small cell carcinoma of the urinary bladder: an immunohistochemical profile of 44 cases.

Small cell carcinoma of the urinary bladder is a rare and aggressive tumor resembling small cell carcinoma of the lung. Thyroid transcription factor 1 (TTF-1) expression is common in small cell carcinomas arising in the lung. However, studies of its expression in extrapulmonary small cell carcinomas have yielded varying results. Because information concerning the immunohistochemical profile of small cell carcinoma of the urinary bladder is limited, we investigated the immunoreactivity of this tumor to a battery of antibodies in a series of 44 cases. Using 5-mum sections cut from paraffin-embedded tissue blocks, immunohistochemistry was performed to detect TTF-1, cytokeratin (CK) 7, CK20, and uroplakin antigenicity in 44 cases of small cell carcinoma of the urinary bladder. None of the patients had primary lung tumors. The TTF-1 immunohistochemical stain showed nuclear positivity in 17 cases (39%). Positive immunostaining for CK7 was observed in 26 cases (59%). There was no positive staining with either CK20 or uroplakin. There was no correlation between TTF-1 expression and survival (P = .27). In addition, TTF-1 expression did not correlate with clinicopathological characteristics, including age (P = .74), sex (P = .53), smoking history (P = .96), clinical stage (P = .10), pathological T stage (P = .50), lymph node metastasis (P = .40), and distant metastasis (P = .58). In summary, TTF-1 expression in small cell carcinoma of the urinary bladder was found in 39% of the tumors, demonstrating that this marker is expressed in small cell carcinomas other than those of pulmonary origin. Small cell carcinoma of the urinary bladder is positive for CK7 immunostaining in 59% of cases consistent with its origin from urothelium. Unlike urothelial carcinoma, expression of CK20 and uroplakin in small cell carcinoma of the urinary bladder is consistently negative, and thus, these stains do not appear to be useful in the diagnosis of this neoplasm. TTF-1 positivity is not a significant prognostic factor in small cell carcinoma of the urinary bladder.

Adult↗
PubMed2005

Molecular genetic evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma.

In most cases, small-cell carcinoma of the urinary bladder is admixed with other histological types of bladder carcinoma. To understand the pathogenetic relationship between the two tumor types, we analyzed histologically distinct tumor cell populations from the same patient for loss of heterozygosity (LOH) and X chromosome inactivation (in female patients). We examined five polymorphic microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21 (IFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20 patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. A nearly identical pattern of allelic loss was observed in the two tumor types in all cases, with an overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed different allelic loss patterns in the two tumor types at a single locus; however, the LOH patterns at the remaining loci were identical. Similarly, the same pattern of nonrandom X chromosome inactivation was present in both carcinoma components in the four cases analyzed. Concordant genetic alterations and X chromosome inactivation between small-cell carcinoma and coexisting urothelial carcinoma suggest that both tumor components originate from the same cells in the urothelium.

Aged↗
PubMed2005

Eosinophilic and classic chromophobe renal cell carcinomas have similar frequent losses of multiple chromosomes from among chromosomes 1, 2, 6, 10, and 17, and this pattern of genetic abnormality is not present in renal oncocytoma.

That chromophobe renal cell carcinoma has an uncommon eosinophilic variant has been recognized for more than a decade. In sections stained with hematoxylin and eosin, the eosinophilic variant of chromophobe renal cell carcinoma and renal oncocytoma are similar in appearance. While it is well established that chromophobe renal cell carcinoma and renal oncocytoma have different patterns of genetic anomalies, little is known of the genetics of the eosinophilic variant of chromophobe renal cell carcinoma. This study was undertaken to elucidate the genetic lesions of eosinophilic chromophobe renal cell carcinoma and to compare them with those found in classic chromophobe renal cell carcinoma and in renal oncocytoma. A total of 29 renal neoplasms--nine eosinophilic chromophobe renal cell carcinomas, 10 classic chromophobe renal cell carcinomas, and 10 oncocytomas--were investigated by fluorescence in situ hybridization on 5 microm paraffin-embedded tissue sections with centromeric probes for chromosomes 1, 2, 6, 10, and 17. Signals were counted in 100-200 neoplastic nuclei from each tumor. Chromophobe renal cell carcinomas frequently showed loss of chromosomes 1 (70% of classic, 67% of eosinophilic), 2 (90% classic, 56% eosinophilic), 6 (80% classic, 56% eosinophilic), 10 (60% classic, 44% eosinophilic), and 17 (90% classic, 78% eosinophilic); Among the classic chromophobe renal cell carcinomas, only one had no loss of any of the chromosomes, while 50% had loss of all five chromosomes. Among the eosinophilic chromophobe renal cell carcinomas, one of nine had no loss and 44% had loss of all five chromosomes. One oncocytoma had loss of chromosome 1. No other chromosomal loss was detected in the oncocytomas. In conclusion, losses of chromosomes 1, 2, 6, 10, and 17 are frequent in both eosinophilic and classic chromophobe renal cell carcinomas. Loss of chromosome 1 occurs occasionally in oncocytoma but losses of chromosomes 2, 6, 10, and 17 are not found in oncocytomas. When the differential diagnostic problem is oncocytoma vs eosinophilic chromophobe renal cell carcinoma, detection of losses of chromosomes 2, 6, 10, or 17 effectively excludes the diagnosis of oncocytoma and supports the diagnosis of chromophobe renal cell carcinoma.

Adenoma, Oxyphilic↗
PubMed2005

c-kit Expression in small cell carcinoma of the urinary bladder: prognostic and therapeutic implications.

The prognosis for small cell carcinoma of the urinary bladder is poor, and strategies for improved therapy are needed. Targeted therapy against the c-kit proto-oncogene has been successful in the management of gastrointestinal stromal tumor. We investigated the expression of c-kit in 52 cases of small cell carcinoma of the urinary bladder. Specimens with more than 10% of cells demonstrating strong membrane staining were considered to have positive immunostaining for c-kit. c-kit expression was detected in 21 of 52 specimens from these patients. Among the 21 specimens, seven had less than 10% staining, and were considered to be negative. Nine had 11-50% staining, and five had more than 50% staining. Overall, 14 of 52 (27%) small cell carcinomas of the urinary bladder were positive for c-kit expression. During a median follow-up of 11 months, 60% of the patients died of bladder cancer. No association was found between c-kit expression and survival or other clinicopathologic parameters. Five-year cancer-specific survivals for c-kit-positive and c-kit-negative tumors were 9 and 15%, respectively (P=0.36). A significant proportion (27%) of small cell carcinomas of the urinary bladder expressed c-kit, suggesting that it may prove useful as a therapeutic target in small cell carcinoma of the urinary bladder.

Adult↗
PubMed2005

Maximum tumor diameter is an independent predictor of prostate-specific antigen recurrence in prostate cancer.

Maximum tumor diameter has been shown to correlate with multiple predictors of clinical outcome in prostate cancer. In the current study, we prospectively analyze whether maximum tumor diameter is a significant predictor of prostate-specific antigen (PSA) recurrence. The study population consisted of 364 patients who underwent radical prostatectomy for prostate cancer. Prostatectomy specimens were evaluated by whole-mount processing of the entire prostate. Maximum tumor diameter was measured from the whole-mount sections of the prostate. Spearman's coefficient of rank correlation was used to correlate tumor diameter with continuous variables. T-tests or analysis of variance (ANOVA) tests were performed to determine if tumor diameter was significantly associated with other clinical and pathologic variables. The effect of clinical and pathologic variables on time to recurrence was analyzed using Cox regression. The mean tumor diameter for all patients was 1.73 cm (range, 0.02-4.40 cm). Maximum tumor diameter was associated with preoperative PSA (r=0.22, P<0.0001), prostate weight (r=-0.12, P=0.028), tumor volume (r=0.87, P<0.0001), Gleason score (r=0.29, P<0.0001), and pathologic stage (P<0.0001). Cox multiple regression was performed to test the prognostic value of maximum tumor diameter adjusting for pathologic stage, Gleason score, and surgical margin status. Increased maximum tumor diameter was associated with shorter time to PSA recurrence (hazard ratio=1.70, 95% confidence interval 1.13-2.56, P=0.01), controlling for risk factors, Gleason score, and surgical margin status. We conclude that maximum tumor diameter is a significant predictor of biochemical recurrence in patients with prostate cancer.

Adult↗
PubMed2005

Anatomic distribution and pathologic characterization of small-volume prostate cancer (<0.5 ml) in whole-mount prostatectomy specimens.

Some investigators consider small-volume prostate cancer (0.5 ml or less) without Gleason pattern 4/5 elements as clinically insignificant. The objective of this study was to characterize the anatomic distribution and pathologic features of small tumors (aggregate volume of 0.5 ml or less) in whole-mount prostatectomy specimens. Between 1999 and 2003, 371 consecutive patients underwent radical prostatectomy at the Indiana University Hospitals for localized prostate cancer. Patients who received hormonal or radiation therapy prior to the surgery were excluded from the study. A total of 62 specimens with total tumor volume of 0.5 ml or less were identified and included in this study. All specimens were embedded and whole-mounted. Tumor volume was measured using the grid method. The mean age at the time of surgery was 59 years (median, 61 years; range, 37-72 years). The mean preoperative prostate-specific antigen (PSA) was 6.5 ng/ml (range: 0.3-18 ng/ml). The mean prostate weight was 53 g (range: 16-132 g). The mean tumor volume was 0.29 ml (median, 0.35 ml; range, 0.02-0.48 ml). Tumor multifocality and bilaterality were present in 69 and 37% of cases, respectively. Three (5%) had positive surgical margins. The largest tumor was located in the peripheral zone, transitional zone, and central zone in 79, 16, and 5% of cases, respectively. The largest tumor was located in the anterior prostate in 10 cases (16%) and in the posterior prostate in 52 cases (84%). The distribution of Gleason scores was 5 (12 cases, 19 %), 6 (40 cases, 65 %), and 7 (10 cases, 16 %). One case had a primary Gleason pattern 4. None had extraprostatic extension, seminal vesicle invasion, or lymph node metastasis. Small-volume prostate cancers are often multifocal and bilateral, with predilection for the peripheral zone. Of these small-volume cases, 16% had Gleason pattern 4 and might, therefore, be clinically significant.

Adult↗
PubMed2005

Preoperative prediction of small volume cancer (less than 0.5 ml) in radical prostatectomy specimens.

PURPOSE: The detection of low volume and early stage prostate cancer has increased with the widespread use of prostate specific antigen screening for prostatic adenocarcinoma. This increased detection has led to efforts to stratify patient risk and the potential benefits of various treatments based on preoperative clinical and biopsy data. We examined various clinical parameters and prostate biopsy features to determine which variables are most predictive of small volume (less than 0.5 ml) cancer at prostatectomy. MATERIALS AND METHODS: We studied 336 patients who underwent prostatectomy for prostate cancer. Radical prostatectomy specimens were completely embedded and whole mounted. Final tumor volume in the radical prostatectomy specimens was determined by the grid method. Clinical data were gathered by a review of patient charts. Various preoperative clinical and biopsy findings were analyzed to determine factors predictive of small volume cancer at prostatectomy. RESULTS: A total of 55 patients (16%) were found to have small volume cancer (less than 0.5 ml). On univariate logistic regression certain variables were significant predictors of small volume cancer, namely the highest Gleason score from all positive biopsy sites (p = 0.001), the Gleason score from the biopsy site with the highest percent of adenocarcinoma (p = 0.006), the highest percent of adenocarcinoma at any biopsy site (p <0.0001), the percent of adenocarcinoma at the biopsy site with the highest Gleason score (p <0.0001), the highest percent of cores positive for adenocarcinoma at any biopsy site (p = 0.001), the percent of cores with carcinoma at the site with the highest Gleason score (p = 0.002), the number of positive sites (p <0.0001) and tumor bilaterality (p <0.0001). None of the clinical parameters that we studied, including preoperative prostate specific antigen (p = 0.52), clinical stage (p = 0.62) or patient age (p = 0.94), was predictive of small volume cancer. On multivariate analysis the highest percent of adenocarcinoma at any site (adjusted OR 0.95, 95% CI 0.92 to 0.97, p <0.0001) and the number of positive biopsy sites (adjusted OR 0.97, 95% CI 0.96 to 0.99, p <0.0001) were significant predictors of small volume cancer. CONCLUSIONS: The number of positive biopsy sites and the highest percent of adenocarcinoma at any biopsy site are significant predictors of small volume cancer in radical prostatectomy specimens.

Adenocarcinoma↗
PubMed2005

Lymphovascular invasion is an independent prognostic factor in prostatic adenocarcinoma.

PURPOSE: Gleason grade and tumor stage are well established prognostic factors in prostate cancer. Histological demonstration of tumor in lymphovascular spaces has been associated with poor prognosis in many tumor types but it is not included in current prostate cancer grading and staging schemes. Whether lymphovascular invasion is an independent prognostic factor for disease progression in prostate cancer is uncertain. We retrospectively investigated lymphovascular invasion as a predictive factor for biochemical failure and cancer specific survival following radical prostatectomy. MATERIALS AND METHODS: The records of 504 patients with prostatic adenocarcinoma undergoing radical prostatectomy were reviewed for lymphovascular invasion. Clinical followup data were available on 459 cases. Mean followup was 44 months (range 1.5 to 144). Multivariate analysis was performed using the Cox model. RESULTS: Lymphovascular invasion was identified in 106 cases (21%). Univariate analysis showed a significant association between lymphovascular invasion and higher preoperative serum prostate specific antigen (PSA), advanced pathological stage, higher Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis and perineural invasion (each p <0.001). No association was observed between lymphovascular invasion and patient age at surgery, prostate weight or high grade prostatic intraepithelial neoplasia. Lymphovascular invasion was an independent predictor of PSA recurrence (HR 1.6, 95% CI 1.12 to 2.38, p = 0.01) and cancer specific survival (HR 2.75, 95% CI 1.04 to 2.28, p = 0.041) after controlling for tumor stage, surgical margins and Gleason grade on multivariate analysis. Five-year cancer specific survival was 90% in men with lymphovascular invasion compared to 98% in those without lymphovascular invasion (p <0.001). CONCLUSIONS: Lymphovascular invasion can be identified in approximately 20% of prostate cancer cases. Lymphovascular invasion is an independent risk factor for PSA recurrence and cancer death in patients with prostate cancer.

Adenocarcinoma↗
PubMed2005

Pleomorphic giant cell carcinoma of the prostate.

We report the clinical and pathologic features of 2 cases of pleomorphic giant cell carcinoma of the prostate. One case was found at autopsy in a 77-year-old man and was composed of high-grade prostatic adenocarcinoma with prominent anaplastic giant cells. The patient presented with metastases to multiple retroperitoneal lymph nodes, liver, and lumbar vertebrae. The second case occurred in a 45-year-old man who underwent transurethral resection of the prostate and was found to have high-grade prostatic adenocarcinoma with an extensive anaplastic giant cell component. The patient presented with distant metastases and died within 9 months. Both regular adenocarcinoma and anaplastic giant tumor cells displayed cytoplasmic immunoreactivity for prostate-specific antigen, prostatic acid phosphatase, and keratin AE1/AE3; in one case, scattered cells were also positive for chromogranin and epithelial membrane antigen. Pleomorphic giant cell carcinoma is a rare variant of prostatic adenocarcinoma with a poor prognosis that should be considered in the differential diagnosis of prostatic pleomorphic tumors.

Adenocarcinoma↗
PubMed2004

OCT4: A sensitive and specific biomarker for intratubular germ cell neoplasia of the testis.

PURPOSE: OCT4 (POU5F1, OCT3) immunostaining highlights pluripotent cells (embryonal carcinoma and seminoma) in primary testicular germ cell tumors, but its relative usefulness in diagnosing intratubular germ cell neoplasia, unclassified (IGCNU) is not well established. The present study aimed to establish OCT4 as a sensitive and specific maker for IGCNU, a putative precursor for adult germ cell tumors. EXPERIMENTAL DESIGN: We evaluated OCT4 immunostaining in 44 cases of IGCNU from patients who had testicular germ cell tumors. In addition, 27 of the 44 IGCNU sections were also examined with antibodies to placenta-like alkaline phosphatase, the most frequently used immunohistochemical marker for intratubular germ cell neoplasia. Sections from the testes of 10 patients who had undergone orchiectomy for hormonal treatment of prostate cancer and from autopsies of 10 patients without histories of germ cell tumors were also examined for OCT4 immunostaining. The immunoreactivity of the autopsy tissues was determined with vimentin staining, and all were reactive. RESULTS: In all 44 of the cases, antibody to OCT4 marked the nuclei of nearly all of the dysplastic cells of intratubular germ cell neoplasia but not non-neoplastic testicular cells. The staining intensity was strong in every case, and there was little or no background staining. All 20 of the control specimens (10 orchiectomy specimens from prostate cancer patients and 10 testes from autopsies) were completely negative for OCT4. The 27 cases that were stained with antiplacenta-like alkaline phosphatase antibodies showed staining of variable intensity in the areas of intratubular germ cell neoplasia, and there was a high level of background staining artifact. CONCLUSIONS: OCT4 is a sensitive and specific maker for intratubular germ cell neoplasia.

Alkaline Phosphatase↗
PubMed2004

Bladder neck invasion is an independent predictor of prostate-specific antigen recurrence.

BACKGROUND: The 1997 TNM staging system for prostatic carcinoma and the 2002 revision thereof classified prostatic carcinoma with bladder neck involvement classified as pT4 disease. This classification is based on the belief that tumors that invade surrounding structures are more aggressive and warrant higher staging than tumors that do not invade surrounding structures. Recent reports in the literature suggested that microscopic involvement of the bladder neck does not carry independent prognostic significance. Therefore, resection specimens with bladder neck involvement should not be classified as pT4. The current study prospectively examined the prognostic significance of bladder neck involvement by prostatic carcinoma. METHODS: The authors analyzed the totally embedded and whole-mounted radical prostatectomy specimens from 364 consecutive patients. The mean patient age was 66 years (range, 41-77 years). The bladder neck, which had been coned from the specimen, was cut in a perpendicular fashion. Involvement of the bladder neck was defined as the presence of neoplastic cells within the smooth muscle bundles of the coned bladder neck. The data were prospectively collected. Bladder neck involvement was analyzed in relation to age, preoperative prostate-specific antigen (PSA) level, prostate weight, Gleason score, final pathologic classification, tumor volume, surgical margin status, the presence of high-grade prostate intraepithelial neoplasm, multifocality, seminal vesicle invasion, extraprostatic extension, perineural invasion, and PSA recurrence. RESULTS: Bladder neck involvement was found in 22 (6%) of 364 patients. Univariate results indicated that bladder neck involvement versus no bladder neck involvement was significantly associated with preoperative PSA (P < 0.001), higher pathologic classification (P < 0.001), larger tumor volume (P < 0.001), extraprostatic extension (P < 0.001), positive surgical margins (P < 0.001), and PSA recurrence (P = 0.003). In a multivariate logistic regression model controlling for pathologic classification, Gleason score, and surgical margin status, bladder neck involvement was an independent predictor of PSA recurrence (P = 0.04). The adjusted odds ratio for bladder neck involvement was 3.3 (95% confidence interval, 1.04-10.03). CONCLUSIONS: In the current study, bladder neck involvement was an independent predictor of early PSA recurrence. The data demonstrated the importance of continued assessment of bladder neck invasion and supported the placement of tumors with bladder neck involvement in a stage that recognizes the prognostic implications of such involvement.

Adult↗
PubMed2004

Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients.

BACKGROUND: Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. Herein, the authors report a series of 64 patients with small cell carcinoma of the urinary bladder. METHODS: Histologic slides and medical records from 64 patients with small cell carcinoma of the urinary bladder were reviewed for morphologic, demographic, and clinical data. All patients fulfilled the criteria established for small cell carcinoma according to the World Health Organization classification system. The 2002 tumor, lymph node, and metastasis (TNM) system was used for pathologic staging. The correlations of various clinicopathologic characteristics with survival were analyzed. RESULTS: Patients ranged in age from 36 years to 85 years (mean age, 66 years). The male-to-female ratio was 3.3:1.0. Among patients with clinical information available, 65% had a history of cigarette smoking, and 88% presented with hematuria. All but one patient had muscle-invasive disease at presentation. Thirty-eight patients (59%) underwent cystectomy. Sixty-six percent of patients had lymph node metastasis at the time of cystectomy. Twenty patients (32%) had pure small cell carcinoma, and 44 patients (68%) had small cell carcinoma with other histologic types (35 patients had urothelial carcinoma, 4 patients had adenocarcinoma, 2 patients had sarcomatoid urothelial carcinoma, and 3 patients had both adenocarcinoma and urothelial carcinoma). With a mean follow-up of 21 months, 68% of patients died of bladder carcinoma. None of the clinicopathologic parameters studied (age, gender, presenting symptoms, smoking history, the presence of a nonsmall cell carcinoma component, chemotherapy, or radiation therapy) were associated with survival. No significant survival difference was found between patients who did and did not undergo cystectomy (P = 0.65). Patients who had organ-confined disease had marginally better survival compared with patients who had nonorgan-confined disease (P = 0.06). The overall, 1-year, 18-month, 3-year, and 5-year disease-specific survival rates were 56%, 41%, 23%, and 16%, respectively. CONCLUSIONS: The prognosis for patients with small cell carcinoma of the urinary bladder remains poor, even though the overall survival for patients with bladder carcinoma has improved significantly over the last decade.

Adenocarcinoma↗