Victor E Reuter

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (531)3078.97 Total impact

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    ABSTRACT: Objectives: To evaluate the recommendations for multiparametric prostate MRI (mp-MRI) interpretation introduced in the recently updated Prostate Imaging Reporting and Data System version 2 (PI-RADSv2), and investigate the impact of pathologic tumour volume on prostate cancer (PCa) detectability on mpMRI. Methods: This was an institutional review board (IRB)-approved, retrospective study of 150 PCa patients who underwent mp-MRI before prostatectomy; 169 tumours ≥0.5-mL (any Gleason Score [GS]) and 37 tumours <0.5-mL (GS ≥4+3) identified on whole-mount pathology maps were located on mp-MRI consisting of T2-weighted imaging (T2WI), diffusion-weighted (DW)-MRI, and dynamic contrast-enhanced (DCE)-MRI. Corresponding PI-RADSv2 scores were assigned on each sequence and combined as recommended by PI-RADSv2. We calculated the proportion of PCa foci on whole-mount pathology correctly identified with PI-RADSv2 (dichotomized scores 1-3 vs. 4-5), stratified by pathologic tumour volume. Results: PI-RADSv2 allowed correct identification of 118/125 (94 %; 95 %CI: 90-99 %) peripheral zone (PZ) and 42/44 (95 %; 95 %CI: 89-100 %) transition zone (TZ) tumours ≥0.5 mL, but only 7/27 (26 %; 95 %CI: 10-42 %) PZ and 2/10 (20 %; 95 %CI: 0-52 %) TZ tumours with a GS ≥4+3, but <0.5 mL. DCE-MRI aided detection of 4/125 PZ tumours ≥0.5 mL and 0/27 PZ tumours <0.5 mL. Conclusions: PI-RADSv2 correctly identified 94-95 % of PCa foci ≥0.5 mL, but was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL. DCE-MRI offered limited added value to T2WI+DW-MRI. Key points: • PI-RADSv2 correctly identified 95 % of PCa foci ≥0.5 mL • PI-RADSv2 was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL • DCE-MRI offered limited added value to T2WI+DW-MRI.
    European Radiology 09/2015; DOI:10.1007/s00330-015-4015-6 · 4.01 Impact Factor
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    ABSTRACT: Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences. To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity. Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes. We described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102). Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p<0.001), RB1 (0.0% vs 18.6%; p<0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed. High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma. Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 08/2015; DOI:10.1016/j.eururo.2015.07.039 · 13.94 Impact Factor
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    ABSTRACT: Sertoli-Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli-Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli-Leydig cell tumors (n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex cord-stromal tumors (n=15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested 2 gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli-Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli-Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; p>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli-Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to occur, to include Sertoli cell tumors and gynandroblastomas. Our results suggest that DICER1 mutations may not play a role in testicular sex cord-stromal tumorigenesis.
    Modern Pathology 08/2015; · 6.19 Impact Factor
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    ABSTRACT: PURPOSE: Tumor size and stage are important prognostic parameters in renal cell carcinoma. While pathologic stage T1 and T2 are defined by size alone, presence of certain intrinsic features can upstage a tumor to pathologic stage T3a regardless of size. We investigate the effect of pathologic tumor stage on the relationship between tumor size and risk of disease recurrence. MATERIALS AND METHODS: Data was reviewed on patients undergoing nephrectomy at our institution between 2006 and 2013 to identify all patients with pathologic stage T1, T2 and T3a tumors. A proportional hazards Cox model was built with time to recurrence as outcome, and pathologic stage and tumor size as covariates. An interaction for stage and tumor size was included. RESULTS: The final cohort included 1,809 patients. On multivariable analysis, when adjusted for tumor size, patients with pT3a tumors had a greater risk of tumor recurrence compared to those with pT1/T2 tumors (HR 3.70, 95% CI 2.31, 5.92, p<0.0001). The risk of disease recurrence increased more rapidly as tumor size increased only with the presence of perinephric fat invasion (p=0.006). CONCLUSIONS: Using the AJCC 2010 staging criteria, we have validated pathologic stage T3a as a poor prognostic factor in renal cell carcinoma, regardless of tumor size. Our results also demonstrated an increased rate of risk for recurrence with perinephric fat invasion. Given this increased risk of recurrence, even in tumors less than 4 cm, closer surveillance is warranted in such patients and the role of perinephric involvement necessitates further investigation.
    The Journal of Urology 08/2015; · 4.47 Impact Factor
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    ABSTRACT: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of 89Zr-DFO-huJ591 (89Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared to conventional imaging modalities (CIMs) and pathology. Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of 89Zr-J591. Whole body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis, and with biopsies of metastatic sites. Median standardized uptake value for 89Zr-J591-positive bone lesions (n = 491) was 8.9; soft tissue lesions (n = 90): 4.8 (p < .00003). 89Zr-J591 detected 491 osseous sites compared to 339 by MDP, and 90 soft tissue lesions compared to 124 by CT. Compared to all CIMs combined, 89Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone, 25 soft tissue) were biopsied in 34 patients; 18/19 89Zr-J591-positive osseous sites and 14/16 89Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of 89Zr-J591 was 95.2% (20/21) for osseous lesions and 60% (15/25) for soft tissue lesions. 89Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft tissue lesions was less optimal, although 89Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed PSMA targeting agents for prostate cancer. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 07/2015; DOI:10.1158/1078-0432.CCR-15-0552 · 8.72 Impact Factor
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    ABSTRACT: Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group. To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data. Between 2005 and 2014, 20 845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions. Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores. In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death. The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 07/2015; DOI:10.1016/j.eururo.2015.06.046 · 13.94 Impact Factor
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    ABSTRACT: Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell 05/2015; 161(5):1215-1228. DOI:10.1016/j.cell.2015.05.001 · 32.24 Impact Factor
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    ABSTRACT: To investigate Haralick texture analysis of prostate MRI for cancer detection and differentiating Gleason scores (GS). One hundred and forty-seven patients underwent T2- weighted (T2WI) and diffusion-weighted prostate MRI. Cancers ≥0.5 ml and non-cancerous peripheral (PZ) and transition (TZ) zone tissue were identified on T2WI and apparent diffusion coefficient (ADC) maps, using whole-mount pathology as reference. Texture features (Energy, Entropy, Correlation, Homogeneity, Inertia) were extracted and analysed using generalized estimating equations. PZ cancers (n = 143) showed higher Entropy and Inertia and lower Energy, Correlation and Homogeneity compared to non-cancerous tissue on T2WI and ADC maps (p-values: <.0001-0.008). In TZ cancers (n = 43) we observed significant differences for all five texture features on the ADC map (all p-values: <.0001) and for Correlation (p = 0.041) and Inertia (p = 0.001) on T2WI. On ADC maps, GS was associated with higher Entropy (GS 6 vs. 7: p = 0.0225; 6 vs. >7: p = 0.0069) and lower Energy (GS 6 vs. 7: p = 0.0116, 6 vs. >7: p = 0.0039). ADC map Energy (p = 0.0102) and Entropy (p = 0.0019) were significantly different in GS ≤3 + 4 versus ≥4 + 3 cancers; ADC map Entropy remained significant after controlling for the median ADC (p = 0.0291). Several Haralick-based texture features appear useful for prostate cancer detection and GS assessment. • Several Haralick texture features may differentiate non-cancerous and cancerous prostate tissue. • Tumour Energy and Entropy on ADC maps correlate with Gleason score. • T2w-image-derived texture features are not associated with the Gleason score.
    European Radiology 05/2015; 25(10). DOI:10.1007/s00330-015-3701-8 · 4.01 Impact Factor
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    The Journal of Urology 04/2015; 193(4):e528-e529. DOI:10.1016/j.juro.2015.02.1549 · 4.47 Impact Factor
  • The Journal of Urology 04/2015; 193(4):e68-e69. DOI:10.1016/j.juro.2015.02.220 · 4.47 Impact Factor
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    The Journal of Urology 04/2015; 193(4):e557. DOI:10.1016/j.juro.2015.02.1534 · 4.47 Impact Factor
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    ABSTRACT: Integrated sequencing analysis identified a group of tumors among clear cell renal cell carcinomas characterized by hotspot mutations in TCEB1 (a gene that contributes to the VHL complex to ubiquitinate hypoxia-inducible factor). We analyzed 11 tumors from two distinct cohorts with TCEB1 mutations along with an expanded cohort to assess whether these should be considered an entity distinct from clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma. All tumors were characterized by hotspot mutations in TCEB1 Y79C/S/F/N or A100P. Morphological and immunohistochemical characteristics of the tumors were assessed by two experienced genitourinary pathologists. Clinical and pathological variables, copy number alterations, mutations, and expression signatures were compared with a cohort of TCEB1 wild-type tumors. All TCEB1-mutated tumors were VHL and PBRM1 wild type and contained distinct copy number profiles including loss of heterozygosity of chromosome 8, the location of TCEB1 (8q21.11). All tumors lacked the clear cell renal cell carcinoma signature 3p loss and contained distinct gene expression signatures. None of the clear cell papillary tumors harbored TCEB1 mutations. Pathologically, all TCEB1-mutated tumors shared characteristic features including thick fibromuscular bands transecting the tumor, pure clear cell cytology frequently with cells showing voluminous cytoplasm, and clear cell renal cell carcinoma-like acinar areas associated with infolding tubular and focally papillary architecture. The presence of voluminous cytoplasm, absence of luminal polarization of tumor nuclei, and lack of extensive cup-like distribution of carbonic anhydrase-IX expression distinguish it from clear cell papillary carcinoma. None of the patients developed metastases at last follow-up (median 48 months). In sum, TCEB1-mutated renal cell carcinoma is a distinct entity with recurrent hotspot mutations, specific copy number alterations, pathway activation, and characteristic morphological features. Further clinical follow-up is needed to determine whether these tumors are more indolent compared with the conventional clear cell renal cell carcinoma.Modern Pathology advance online publication, 13 February 2015; doi:10.1038/modpathol.2015.6.
    Modern Pathology 02/2015; 28(6). DOI:10.1038/modpathol.2015.6 · 6.19 Impact Factor
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    ABSTRACT: Background The handling and reporting of testicular tumours is difficult due to their rarity.DesignA survey developed by the European Network of Uro-Pathology (ENUP) and sent to its members and experts to assess the evaluation of testicular germ cell tumoursResults25 experts (E) and 225 ENUP members replied. Areas of disagreement included immaturity in teratomas, reported by 32% (E) but 68% (ENUP). Although the presence of rete testis invasion was widely reported, the distinction between pagetoid and stromal invasion was made by 96% (E) but only 63% (ENUP). Immunohistochemistry was used in more than 50% of cases by 68% (ENUP) and 12% (E). Staging revealed the greatest areas of disagreement. Invasion of the tunica vaginalis without vascular invasion was interpreted as T1 by 52% (E) and 67% (ENUP), but T2 by the remainder. Tumour invading the hilar adipose tissue adjacent to the epididymis without vascular invasion was interpreted as T1: 40% (E), 43% (ENUP), T2: 36% (E), 30% (ENUP) and T3: 24% (E), 27% (ENUP).Conclusions There is remarkable consensus in many areas of testicular pathology. Significant areas of disagreement included staging and reporting of histologic types, both of which have the potential to impact on therapy.This article is protected by copyright. All rights reserved.
    Histopathology 01/2015; 67(3). DOI:10.1111/his.12657 · 3.45 Impact Factor
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    ABSTRACT: Context .- While biopsies are now increasingly being performed for the diagnosis of renal cortical neoplasms, the influence of the rendered pathological diagnoses on the clinical management is only rarely documented. Objectives .- To report our experience with consecutively performed renal biopsies and the potential impact of the diagnosis on subsequent clinical management. Design .- Material from needle biopsies performed consecutively at our institution between 2006 and 2011 was reviewed. The influence of the reported pathology results on the clinical management was determined from patient follow-up medical record review. Results .- In total, 218 percutaneous biopsies for renal masses were performed during this period. Among them, 181 (83%) yielded neoplastic tissue, including 81 clear cell renal cell carcinomas, 29 low-grade oncocytic neoplasms, 7 papillary renal cell carcinomas, 5 clear cell papillary renal cell carcinomas, 5 angiomyolipomas, and 14 urothelial carcinomas. Fourteen additional cases (6%) contained lesional material from clinically known nonneoplastic processes, for a total diagnostic yield of 89%. Twenty-three (11%) were nonrepresentative of lesional tissue. In 10 of these, repeat biopsies or resections established the diagnosis of renal tumors. Biopsy diagnosis was confirmed in 29 of 30 cases (97%) on subsequent nephrectomy. Following the biopsy diagnosis, there were significant differences in the clinical management; overall, 79% of clear cell renal cell carcinomas received therapeutic interventions, and 17% were put on active surveillance. In contrast, 77% of the benign or low-grade lesions were put on active surveillance. Conclusions .- Accurate and specific diagnosis can be rendered on renal core biopsy in most renal tumors, and the biopsy diagnosis can have a definitive role in their clinical management.
    Archives of pathology & laboratory medicine 12/2014; 138(12):1673-9. DOI:10.5858/arpa.2013-0574-OA · 2.84 Impact Factor
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    ABSTRACT: The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.Modern Pathology advance online publication, 21 November 2014; doi:10.1038/modpathol.2014.158.
    Modern Pathology 11/2014; 28(5). DOI:10.1038/modpathol.2014.158 · 6.19 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):987-987. DOI:10.1158/1538-7445.AM2014-987 · 9.33 Impact Factor
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    ABSTRACT: Background: Aberrations in ERBB2 (both amplification and mutations) and ERBB3 represent a novel therapeutic avenue for HER2/HER3-targeted therapy. A minority of urothelial carcinoma (UC) is known to have ERBB2 amplification but little is known about ERBB2 and ERBB3 mutations in this disease. We identified a cohort of UC with ERBB2/ERBB3 mutations using a next generation sequencing platform and performed detailed histopathologic evaluation and immunohistochemistry for HER2. Methods: A total of 138 UC cases were studied. Frozen tumor tissue and matching germline DNA from peripheral blood were analyzed using a targeted, deep-sequencing assay designed to identify point mutations, indels, and copy number alterations in 300 cancer-associated genes, including ERBB2 and ERBB3. HER2 IHC was performed on the confirmed mutant UCs and on 14 randomly selected cases from the cohort that were without ERBB2/ERBB3 mutations or amplification. Results: ERBB2 mutations were identified in 15 cases (11%). There were 14 missense mutations and one frameshift mutation. Two HER2 mutant UCs also exhibited ERBB2 amplification. ERBB3 mutations were identified in 17 cases (12%), all of which were missense mutations. Three cases had concurrent ERBB2 and ERBB3 mutations (2%).The majority of the ERBB2/ERBB3 mutant tumors did not exhibit HER2 overexpression as determined by intense and diffuse membranous staining by IHC. Only 4 mutant cases had 3+ staining, 2 of which also had HER2 amplification. Many tumors with wild-type ERBB2 and ERBB3 expressed HER2 at variable intensity but none as 3+. Conclusions: Mutations in ERBB2 and ERBB3 are present in a significant minority of urothelial carcinoma and may represent targets for anti-HER2 and anti-HER3 therapy. HER2 immunohistochemistry is not a sensitive method for identifying tumors with ERBB2/ERBB3 mutations.
    Pathology 10/2014; 46:S138. DOI:10.1097/01.PAT.0000454567.82822.1a · 2.19 Impact Factor
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    ABSTRACT: We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.
    Cancer Cell 09/2014; 26:319-330. · 23.52 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S88. DOI:10.1016/j.ijrobp.2014.05.481 · 4.26 Impact Factor
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    ABSTRACT: Purpose: Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. (89)Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection. Methods: Ten patients with metastatic prostate cancer received 5 mCi of (89)Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by (89)Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of (89)Zr-huJ591 was done. Optimal time for imaging post-injection was determined. Results: The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of (89)Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1-14 h) and 62 ± 13 h (range 51-89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153-317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on (89)Zr-huJ591, while the remaining 11 lesions were (89)Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on (89)Zr-huJ591 study, while the conventional imaging modality was negative. Conclusion: (89)Zr-huJ591 PET imaging of prostate-specific membrane antigen expression is safe and shows good localization of disease in prostate cancer patients. Liver is the critical organ for dosimetry, and 7 ± 1 days is the optimal imaging time. A larger study is underway to determine lesion detection in an expanded cohort of patients with metastatic prostate cancer.
    European journal of nuclear medicine and molecular imaging 08/2014; 41(11). DOI:10.1007/s00259-014-2830-7 · 5.38 Impact Factor

Publication Stats

27k Citations
3,078.97 Total Impact Points


  • 1987–2015
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Pathology
      • • Department of Medicine
      • • Department of Surgery
      New York, New York, United States
  • 2013
    • American Urological Association
      Linthicum, Maryland, United States
  • 2010–2013
    • Gracie Square Hospital, New York, NY
      New York, New York, United States
    • University of São Paulo
      San Paulo, São Paulo, Brazil
    • Credit Valley Hospital
      Mississauga, Ontario, Canada
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States
  • 1999–2013
    • Cornell University
      • Department of Pathology and Laboratory Medicine
      Итак, New York, United States
  • 2003–2010
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, MD, United States
  • 2008
    • Winthrop University Hospital
      • Division of Surgical Pathology
      Mineola, New York, United States
    • Columbia University
      New York, New York, United States
  • 2006
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2004
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2001
    • Georgia Health Sciences University
      • Department of Pathology
      Augusta, GA, United States
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      • Department of Medicine
      Torrance, California, United States
  • 1998
    • Universidad Nacional de Asunción
      • Facultad de Ciencias Médicas
      San Lorenzo del Campo Grande, Central, Paraguay
  • 1990–1998
    • Memorial Hospital, TN
      Chattanooga, Tennessee, United States
  • 1997
    • Henry Ford Hospital
      • Surgery
      Detroit, Michigan, United States
  • 1991
    • Lexington Medical Center
      West Columbia, South Carolina, United States