B Czerniak

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (162)784.82 Total impact

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    ABSTRACT: The 8th Annual Bladder Cancer Think Tank (BCAN-TT ) brought together a multidisciplinary group of clinicians, researchers, and patient advocates in an effort to advance bladder cancer research.
    Urologic oncology. 07/2014;
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    ABSTRACT: Whole-genome analyses have revealed that muscle-invasive bladder cancers (MIBCs) are heterogeneous and can be grouped into basal and luminal subtypes that are highly reminiscent of those found in breast cancer. Basal MIBCs are enriched with squamous and sarcomatoid features and are associated with advanced stage and metastatic disease at presentation. Like basal breast cancers, basal bladder tumours contain a claudin-low subtype that is enriched with biomarkers characteristic of epithelial-to-mesenchymal transition. The stem cell transcription factor ΔNp63α controls basal MIBC gene expression, just as it does in basal breast cancers. Luminal MIBCs are enriched with activating FGFR3 and ERBB3 mutations and ERBB2 amplifications, and their gene expression profiles are controlled by peroxisome proliferator activator receptor γ (PPARγ) and possibly also by oestrogen receptor activation. Luminal bladder cancers can be further subdivided into two subtypes, p53-like and luminal, which can be distinguished from one another by different levels of biomarkers that are characteristic of stromal infiltration, cell cycle progression, and proliferation. Importantly, basal bladder cancers are intrinsically aggressive, but are highly sensitive to cisplatin-based combination chemotherapy. Although the luminal subtypes are not as intrinsically aggressive as basal cancers, p53-like tumours are resistant to chemotherapy and might, therefore, represent a problem for treated patients.
    Nature Reviews Urology 06/2014; · 4.79 Impact Factor
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    ABSTRACT: Muscle-invasive bladder cancers (MIBCs) are biologically heterogeneous and have widely variable clinical outcomes and responses to conventional chemotherapy. We discovered three molecular subtypes of MIBC that resembled established molecular subtypes of breast cancer. Basal MIBCs shared biomarkers with basal breast cancers and were characterized by p63 activation, squamous differentiation, and more aggressive disease at presentation. Luminal MIBCs contained features of active PPARγ and estrogen receptor transcription and were enriched with activating FGFR3 mutations and potential FGFR inhibitor sensitivity. p53-like MIBCs were consistently resistant to neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and all chemoresistant tumors adopted a p53-like phenotype after therapy. Our observations have important implications for prognostication, the future clinical development of targeted agents, and disease management with conventional chemotherapy.
    Cancer cell 02/2014; 25(2):152-65. · 25.29 Impact Factor
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    ABSTRACT: GATA-3 is a novel immunohistochemical marker for urothelial carcinoma (UC); however, few studies have investigated GATA-3’s role as a marker for UC variants. We used immunohistochemistry to assess GATA-3 expression in different UC variants, including micropapillary (n=46), sarcomatoid (n=43), small cell carcinoma (n=22), and plasmacytoid (n=16) variants, and we also compared GATA-3 expression in conventional bladder UC (n=103) to that in squamous cell carcinoma (n=14). GATA-3 expression was present in 70% (72/103) of conventional bladder UCs and highly concordant between matched primary and metastatic UCs. The GATA-3 expression levels of the micropapillary variants (57%; 26/46) and plasmacytoid variants (44%; 7/16) were not significantly different from that of conventional UC. However, the GATA-3 expression levels of the sarcomatoid variants (16%; 7/43) and small-cell carcinoma variants (5%; 1/22), which only weakly expressed the protein, were significantly lower than that of conventional UC (P<0.001). Only 7% of squamous cell carcinomas (1/14) expressed GATA-3, and it was also significantly lower than that of conventional UC (P<0.001). GATA-3 expression was not significantly associated with tumor stage or patients’ clinical outcomes. In conclusion, GATA-3 expression differed among UC variants. GATA-3 is a useful marker for confirming the urothelial origin of micropapillary and plasmacytoid UC variants but not that of sarcomatoid or small-cell carcinoma variants. GATA-3 can also be used in differentiating UC from squamous cell carcinoma.
    Human pathology 01/2014; · 3.03 Impact Factor
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    ABSTRACT: Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role in controlling chromosome number but not the proliferation of bladder cancer cells. These findings identify STAG2 as one of the most commonly mutated genes in bladder cancer.
    Nature Genetics 10/2013; · 35.21 Impact Factor
  • Melissa L Stanton, Li Xiao, Bogdan A Czerniak, Charles C Guo
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    ABSTRACT: Context.-Urothelial tumors are rare in young patients. Because of their rarity, the natural history of the disease in young patients remains poorly understood. Objective.-To understand the pathologic and clinical features of urothelial tumors of the urinary bladder in young patients. Design.-We identified 59 young patients with urothelial tumors of the urinary bladder treated at our institution and analyzed the tumors' pathologic features and the patients' clinical outcomes. Results.-All patients were 30 years or younger, with a mean age of 23.5 years (range, 4-30). Thirty-eight patients (64%) were male, and 21 (36%) were female. Most tumors were noninvasive, papillary urothelial tumors (49 of 59; 83%), including papillary urothelial neoplasms of low malignant potential (7 of 49; 14%), low-grade papillary urothelial carcinomas (38 of 49; 78%), and high-grade papillary urothelial carcinomas (4 of 49; 8%). Only a few (n = 10) of the urothelial tumors were invasive, invading the lamina propria (n = 5; 50%), muscularis propria (n = 4; 40%), or perivesical soft tissue (n = 1; 10%). Clinical follow-up information was available for 41 patients (69%), with a mean follow-up time of 77 months. Of 31 patients with noninvasive papillary urothelial tumors, only 1 patient (3%) later developed an invasive urothelial carcinoma and died of the disease, and 30 of these patients (97%) were alive at the end of follow-up, although 10 (32%) had local tumor recurrences. In the 10 patients with invasive urothelial carcinomas, 3 patients (30%) died of the disease and 5 others (50%) were alive with metastases (the other 2 [20%] were alive with no recurrence). Conclusion.-Urothelial tumors in young patients are mostly noninvasive, papillary carcinomas and have an excellent prognosis; however, a small subset of patients may present with high-grade invasive urothelial carcinomas that result in poor clinical outcomes.
    Archives of pathology & laboratory medicine 10/2013; 137(10):1337-1341. · 2.78 Impact Factor
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    ABSTRACT: We evaluated survival of patients with muscle-invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy. We identified patients with muscle-invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were deemed high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histologic evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease-specific, progression-free, and overall) and rate of pathological upstaging. An independent cohort of patients from a separate institution was used to confirm our findings. We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased five-year overall survival (47.0 vs. 64.8%) and decreased disease-specific (64.3 vs. 83.5%) and progression-free (62.0 vs. 84.1%) survival probabilities compared to low risk patients (p<0.001). Survival outcomes were confirmed in the validation subset. On final pathology, 49.2% of low risk patients were upstaged. Five-year disease-specific survival of low risk patients was above 80%, supporting the distinction of high and low risk muscle-invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those who are low risk can undergo upfront surgery with good expectations and avoid chemotherapy-associated toxicity.
    The Journal of urology 07/2013; · 4.02 Impact Factor
  • William P Tarrant, Bogdan A Czerniak, Charles C Guo
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    ABSTRACT: Testicular germ cell tumors (GCTs) commonly metastasize to the retroperitoneal lymph nodes (RPLNs). We evaluated 100 cases of RPLN dissection specimens with viable GCTs after chemotherapy and compared them with their corresponding orchiectomy specimens. The mean age of patients was 28 years (range, 15-58 years). The testicular tumors consisted of mixed GCT (n = 72), teratoma (n = 18), seminoma (n = 4), embryonal carcinoma (n = 3), yolk sac tumor (n = 1), and no viable tumor (n = 2). Somatic malignant components were found in 5 cases. The metastatic tumors in the RPLNs consisted of only teratoma (n = 77) and non-teratomatous GCT (n = 23). Twenty-one patients had only teratoma in the RPLNs but not in the testis, and 10 patients had metastatic non-teratomatous GCT components that were not observed in the testis. Six patients had somatic malignant components in the RPLNs, but only one of them had such a component in the testis. Overall, 13 patients died of disease in a mean of 42 months, and the patients with only teratoma in the RPLNs had a lower mortality rate (9%) than those with non-teratomatous components (26%) (P = .044). One patient with somatic components in the primary GCT and 3 patients with somatic components in the metastases died of disease. Our study demonstrates that there is frequent discordance of histologic composition between primary and metastatic testicular GCTs. Teratoma is the most common component in treated GCTs and is usually associated with a more favorable clinical outcome than non-teratomatous GCTs. The presence of somatic components in the RPLNs metastasis indicates a poor prognosis.
    Human pathology 07/2013; · 3.03 Impact Factor
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    ABSTRACT: Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
    Nature 06/2013; · 38.60 Impact Factor
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    ABSTRACT: Activating mutations of Fibroblast growth factor receptor-3 (FGFR3) have been described in approximately 75% of low-grade papillary bladder tumors. In muscle invasive disease, FGFR3 mutations are found in 20% of tumors, but overexpression of FGFR3 is observed in about half of cases. Therefore, FGFR3 is a particularly promising target for therapy in bladder cancer. Up to now most drugs tested for inhibition of FGFR3 have been small molecule, multi-tyrosine kinase inhibitors. More recently, a specific inhibitory monoclonal antibody targeting FGFR3 (R3Mab) has been described and tested pre-clinically. In this study, we have evaluated mutation and expression status of FGFR3 in 19 urothelial cancer cell lines and a cohort of 170 American bladder cancer patients. We demonstrated inhibitory activity of R3Mab on tumor growth and corresponding cell signaling in three different orthotopic xenografts of bladder cancer. Our results provide the pre-clinical proof of principle necessary to translate FGFR3 inhibition with R3Mab into clinical trials in patients with bladder cancer.
    Molecular Cancer Therapeutics 05/2013; · 5.60 Impact Factor
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    ABSTRACT: Genomic abnormalities, such as deletions in 11q22 or 17p13, are associated with poorer prognosis in patients with chronic lymphocytic leukemia (CLL). We hypothesized that unknown regions of copy number variation (CNV) affect clinical outcome and can be detected by array-based single-nucleotide polymorphism (SNP) genotyping. We compared SNP genotypes from 168 untreated patients with CLL with genotypes from 73 white HapMap controls. We identified 322 regions of recurrent CNV, 82 of which occurred significantly more often in CLL than in HapMap (CLL-specific CNV), including regions typically aberrant in CLL: deletions in 6q21, 11q22, 13q14, and 17p13 and trisomy 12. In univariate analyses, 35 of total and 11 of CLL-specific CNVs were associated with unfavorable time-to-event outcomes, including gains or losses in chromosomes 2p, 4p, 4q, 6p, 6q, 7q, 11p, 11q, and 17p. In multivariate analyses, six CNVs (ie, CLL-specific variations in 11p15.1 to 15.4 or 6q27) predicted time to treatment or overall survival independently of established markers of prognosis. Moreover, genotypic complexity (ie, the number of independent CNVs per patient) significantly predicted prognosis, with a median time to treatment of 64 months versus 23 months in patients with zero to one versus two or more CNVs, respectively (P = 3.3 × 10(-8)). In summary, a comparison of SNP genotypes from patients with CLL with HapMap controls allowed us to identify known and unknown recurrent CNV and to determine regions and rates of CNV that predict poorer prognosis in patients with CLL.
    The Journal of molecular diagnostics: JMD 12/2012; · 3.48 Impact Factor
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is a physiological process that plays important roles in tumor metastasis, stemness, and drug resistance. EMT is typically characterized by the loss of the epithelial marker E-cadherin and increased expression of EMT-associated transcriptional repressors, including ZEB1 and ZEB2. The miR-200 family and miR-205 prevent EMT through suppression of ZEB1/2. p53 has been implicated in the regulation of miR-200c, but the mechanisms controlling miR-205 expression remain elusive. Here we report that the p53 family member and p63 isoform, Np63α, promotes miR-205 transcription and controls EMT in human bladder cancer cells. Np63α, E-cadherin and miR-205 were co-expressed in a panel of bladder cancer cell lines (n=28) and a cohort of primary bladder tumors (n=98). Stable knockdown (KD) of Np63α in the epithelial bladder cancer cell line UM-UC6 decreased the expression of miR-205 and induced the expression of ZEB1/2, effects that were reversed by expression of exogenous miR-205. Conversely, overexpression of Np63α in the mesenchymal bladder cancer cell line UM-UC3 induced miR-205 and suppressed ZEB1/2. Np63α KD reduced the expression of the primary and mature forms of miR-205 and the miR-205 host gene (miR-205HG) and decreased binding of RNA Pol II to the miR-205HG promoter, inhibiting miR-205HG transcription. Finally, high miR-205 expression was associated with adverse clinical outcomes in bladder cancer patients. Together, our data demonstrate that Np63α-mediated expression of miR-205 contributes to the regulation of EMT in bladder cancer cells and identify miR-205 as a molecular marker of the lethal subset of human bladder cancers.
    Journal of Biological Chemistry 12/2012; · 4.65 Impact Factor
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    ABSTRACT: PURPOSE: Plasmacytoid urothelial carcinoma (PUC) is a rare variant histology with poorly defined clinical behavior. We report clinical outcomes information on patients with predominant PUC. MATERIALS AND METHODS: Retrospective analysis of treatments and outcomes in patients with predominant PUC seen at MD Anderson Cancer Center from 1990-2010. Kaplan-Meier method was used to calculate Overall (OS) and progression-free survival (PFS). RESULTS: 31 patients were identified (median age:63.5yrs; 83.3% male; TNM stage:cT1N0,n=4;cT2N0,n=7;cT3b-4aN0,n=5; cT4b, N+ or M+ n = 15). Median OS for all patients was 17.7months (Stage I-III vs IV: 45.8 vs 13.3mo). Of 16 patients with potentially surgically resectable PUC (<=pT4aN0M0) 5 received neo-adjuvant chemotherapy, 10 had initial surgery, and one was treated with TURBT alone. Despite pathologic downstaging in 80% of patients treated with neo-adjuvant chemotherapy, relapses were common and there was no difference in survival between patients treated with neo-adjuvant chemotherapy compared to initial surgery, even though adjuvant chemotherapy was given in 7 patients. Surgical upstaging with positive margins was also common with surgery alone. The most common site of recurrence was in the peritoneum (19/23), with relapses occurring even in those with pCR at surgery. In patients presenting with metastatic disease who were treated with chemotherapy, the median survival was 12.6 months. CONCLUSIONS: PUC is a very aggressive subset with overall poor outcomes. Although downstaging is seen with neoadjuvant chemotherapy, there are few long-term survivors. There is a strong predilection for recurrences along the peritoneal lining.
    The Journal of urology 11/2012; · 4.02 Impact Factor
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    ABSTRACT: We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival.
    PLoS ONE 01/2012; 7(8):e42452. · 3.53 Impact Factor
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    ABSTRACT: Langerhans cell histiocytosis (LCH) has a challenging and still unclear pathogenesis. A body of literature points to impaired maturation of the lesional dendritic cells, and to immune dysregulation in the form of increased FoxP3 cells. Various cytokine abnormalities such as expression of transforming growth factor (TGF)-β have been reported, as well as abnormalities in lipid content in LCH cells. Morphoproteomic techniques were applied to identify the signal transduction pathways that could influence histogenesis and immune regulation in osteolytic LCH. Five pediatric cases of osteolytic LCH were examined, using antibodies against CD1a, S100, CD68, CD8, FoxP3, phosphorylated (p)-STAT3 (Tyr705), protein kinase C (PKC)-α, phospholipase (PL)D1, fatty acid synthase (FASN), and zinc finger protein, Gli2. Positive and negative controls were performed. A FoxP3(+)/CD8(+) cell ratio was calculated by counting the FoxP3+ and CD8+ cells in 10 high power fields for each case. There is induction of sonic hedgehog (SHH) mediators consistent with TGF-β signaling pathway through Smad3-dependent activation of Gli2, findings supported by the plasmalemmal and cytoplasmic expression of PKC-α and PLD1, and nuclear expression of Gli2, in lesional cells. The FoxP3+/CD8+ cell ratio is increased, ranging from 1.7-7.94. There is moderate cytoplasmic expression of FASN in most of the Langerhans cells, a finding that supports previously published phospholipid abnormalities in LCH and is consistent with PKC-α/PLD1/TGF-β signaling. With our study, we strongly suggest that the TGF-β cell signaling pathway is a major player in the pathogenesis of LCH, leading to non-canonical induction of nuclear Gli2 expression, thereby contributing to osteoclastogenesis in LCH histiocytes. It could also cause a state of immune frustration in LCH, by inducing the transformation of CD4(+)CD25(-) cells into CD4(+)/FoxP3(+) cells. This coincides with the clinical evidence of a response to thalidomide in patients with osteolytic LCH, given its reported ability to reduce TGF-beta 1 and FoxP3 cells. Such TGF-β signaling in osteoclastogenesis and immune dysregulation, and the presence of FASN in the majority of cells, have additional therapeutic implications for osteolytic LCH.
    International journal of clinical and experimental pathology 01/2012; 5(6):503-11. · 2.24 Impact Factor
  • Human pathology 01/2012; 43(1):151-152. · 3.03 Impact Factor
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    ABSTRACT: The cDNA expression libraries that produce correct proteins are essential in facilitating the identification of protein-protein interactions. The 5'-untranslated regions (UTRs) that are present in the majority of mammalian and non-mammalian genes are predicted to alter the expression of correct proteins from cDNA libraries. We developed a novel cDNA expression library from which 5'-UTRs were removed using a mixture of polymerase chain reaction primers that complement the Kozak sequences we refer to as an "in-frame cDNA library." We used this library with the protein complementation assay to identify two novel binding partners for ras-related ADP-ribosylation factor-like 11 (ARL11), cellular retinoic acid binding protein 2 (CRABP2), and phosphoglycerate mutase 1 (PGAM1). Thus, the in-frame cDNA library without 5'-UTRs we describe here increases the chance of correctly identifying protein interactions and will have wide applications in both mammalian and non-mammalian detection systems.
    PLoS ONE 01/2012; 7(12):e52290. · 3.53 Impact Factor
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    ABSTRACT: Recent studies have revealed the presence of TMPRSS2-ERG gene fusion in both primary and metastatic prostate cancers. However, the relationship between primary and corresponding metastatic prostate cancers with respect to the status of this gene fusion remains unclear. Using fluorescence in situ hybridization, we evaluated the rearrangement of the ERG gene in the radical prostatectomy specimens and corresponding lymph node metastases from 19 patients with prostate cancer. The mean age of the patients was 61 years, and the median Gleason score in the radical prostatectomy specimens was 7 (4 + 3). Prostate cancer was unifocal in 6 cases and multifocal in 13 cases, including 10 with 2 foci and 3 with 3 foci. In the primary prostate cancers, rearrangement of the ERG gene was observed in 13 cases and associated with deletion of the 5' ERG gene in 8 cases. In the metastases, the ERG rearrangement was present in 10 cases and associated with deletion of the 5' ERG gene in 6 cases. In unifocal prostate cancers, the status of the ERG rearrangement was concordant between the primary prostate cancer and metastasis in 5 of 6 cases. In multifocal prostate cancer, despite a significant interfocal discordance, the status of the ERG rearrangement was concordant between the index (largest) primary tumor focus and metastasis in all 13 cases. Our study demonstrates a close relationship of the TMPRSS2-ERG gene fusion status between primary and metastatic prostate cancer. The concordance of the ERG gene rearrangement status between the index primary tumor focus and metastasis suggests that metastasis most likely arises from the index tumor focus in multifocal prostate cancer.
    Human pathology 09/2011; 43(5):644-9. · 3.03 Impact Factor
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    ABSTRACT: Significant morbidity and expense result from frequent recurrences of nonmuscle-invasive bladder cancer (NMIBC) after standard treatment, and carcinoma in situ (Tis) is a poor prognostic factor. Predicated on observational and preclinical data strongly supporting cyclooxygenase-2 (COX-2) in the pathogenesis, and the activity of COX-2 inhibitors, in bladder cancer, we conducted a randomized, double-blind, placebo-controlled trial to determine whether celecoxib could reduce the time-to-recurrence (TTR) in NMIBC patients at high risk for recurrence. A total of 146 patients were randomized to celecoxib (200 mg) or placebo orally twice daily for at least 12 months. The average treatment duration was 1.25 years. Primary intent-to-treat analysis revealed celecoxib did not statistically significantly prolong TTR compared with placebo (P = 0.17, log rank) with a median follow-up of 2.49 years. The recurrence-free rate at 12 months with celecoxib was 88% (95% CI: 0.81-0.96) versus 78% (95% CI: 0.69-0.89) with placebo. After controlling for covariates with Cox regression analysis, recurrence rates did not differ between the two study arms (HR = 0.69; 95% CI: 0.37-1.29). However, celecoxib had a marginally significant effect on reducing metachronous recurrences (vs. placebo) with HR of 0.56 (95% CI: 0.3-1.06; P = 0.075). Celecoxib was well tolerated, with similar adverse events and quality-of-life in both arms. Our clinical trial results do not show a clinical benefit for celecoxib in preventing NMIBC recurrence but further investigation of COX-2 inhibitors in this setting is warranted.
    Cancer Prevention Research 08/2011; 4(10):1580-9. · 4.89 Impact Factor
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    ABSTRACT: Small cell carcinoma of the kidney is distinctively rare. We searched pathology files in 2 institutions and found 14 cases of renal small cell carcinoma. The patients' mean age at diagnosis was 59 years (range, 22-75 years); 8 were women, and 6 were men. Patients usually presented with hematuria (n = 6) and abdominal pain (n = 5). The mean tumor size was 7.1 cm (range, 3.5-14.0 cm). The small cell carcinoma was pure in 9 cases and mixed with high-grade urothelial carcinoma in 5 cases. None was associated with any type of renal cell carcinoma. Tumor necrosis was present in all cases, and lymphovascular invasion was identified in 6 cases. The tumor invaded the perinephric adipose tissue in 13 cases and was confined to the kidney in only 1 case. Lymph node metastases were identified in all patients who underwent lymph node dissection (5/5). On immunostains, the small cell carcinoma cells were positive for pancytokeratin (11/12), chromogranin (6/9), and synaptophysin (8/9). Follow-up data were available for 13 patients, and 11 died of small cell carcinoma at a mean of 15 months (range, 4-31 months) after diagnosis. Of the 2 surviving patients, 1 was alive at 5 months after diagnosis, and the other, whose disease was confined to the kidney, was alive with no evidence of disease at 137 months. In summary, renal small cell carcinoma is a highly aggressive disease that often presents at an advanced stage with widespread metastases. Patients usually have a poor clinical outcome despite multimodal therapy. The frequent coexistence of small cell carcinoma with urothelial carcinoma suggests that renal small cell carcinomas may evolve from a preexisting urothelial carcinoma.
    Human pathology 07/2011; 42(11):1792-8. · 3.03 Impact Factor

Publication Stats

3k Citations
784.82 Total Impact Points

Institutions

  • 1995–2014
    • University of Texas MD Anderson Cancer Center
      • • Department of Pathology
      • • Division of Pathology and Laboratory Medicine
      Houston, Texas, United States
  • 2011
    • University of Houston
      Houston, Texas, United States
  • 2004–2008
    • University of Texas Southwestern Medical Center
      • Hamon Center for Therapeutic Oncology Research
      Dallas, TX, United States
  • 1999–2000
    • Otto-von-Guericke-Universität Magdeburg
      • Institute for Pathology
      Magdeburg, Saxony-Anhalt, Germany
  • 1985–1995
    • Albert Einstein College of Medicine
      • • Orthopaedic Surgery
      • • Department of Pathology
      New York City, NY, United States
  • 1987–1991
    • Montefiore Medical Center
      • Department of Pathology
      New York City, NY, United States