Jasreman Dhillon

Moffitt Cancer Center, Tampa, Florida, United States

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Publications (21)49.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed clear cell A (ccA) and clear cell B (ccB). The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34. Patients and methods: In this retrospective analysis, 282 patients from Moffitt Cancer Center with ccRCC with gene expression analyses of the primary tumor were identified and ClearCode34 was applied to identify tumors as ccA or ccB. The medical record and institutional databases were queried to define patient characteristics, comorbidities, and outcomes. Results: We validated in this external cohort the superior overall survival, cancer-specific survival, and recurrence-free survival of ccA patients relative to ccB patients (P<0.001). Addressing other clinical characteristics, the ccA patients were more likely to be obese (48% vs. 34%, P = 0.021) and diabetic (26% vs. 13%, P = 0.035). The ccA patients also trended toward having been more frequent users of angiotensin system inhibitors (71% vs. 52%, P = 0.055). In multivariate analyses, ccB status is independently associated with inferior cancer-specific survival (hazard ratio = 3.26, 95% confidence interval: 1.84-5.79) and overall survival (hazard ratio = 2.50, 95% confidence interval: 1.53-4.08). Conclusions: ClearCode34, after considering distinct patterns of comorbidities in each molecular subtype, remains a strong prognostic tool in patients with ccRCC. Obesity and diabetes mellitus emerged as factors that may influence ccRCC phenotypes and further studies investigating the effect of these metabolic conditions functionally onto tumor biology are warranted. Additionally, use of angiotensin system inhibitors could be studied in the context of ccRCC molecular classification in future studies to better understand its effect on ccRCC outcomes.
    Urologic Oncology 11/2015; DOI:10.1016/j.urolonc.2015.09.015 · 2.77 Impact Factor
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    ABSTRACT: Urachal carcinoma is a rare tumor that has not been well studied. To determine the pathologic and clinical features of this disease, we retrospectively evaluated 46 cases from our surgical pathology files. The patients included 16 women and 30 men, with a mean age of 53.4 years (range, 28-82 years). Forty patients had undergone cystectomy, and the remaining 6 had undergone transurethral bladder biopsy. Most tumors were located at the dome (n = 44); only 2 were located at both the dome and anterior wall. All tumors consisted of adenocarcinoma, including mucinous (n = 36), enteric (n = 7), not otherwise specified (n = 2), and signet ring cell (n = 1) types. Focal areas of signet ring cell features were present in 23 cases, but urothelial carcinoma in situ was not identified in any cases. The tumors invaded the muscularis propria (n = 8), perivesical adipose tissue (n = 27), and abdominal wall (n = 3). Twenty-five patients had died of cancer at a mean of 32 months (range, 12-74 months), and 21 patients were alive at a mean of 65 months (range, 7-230 months). The median cancer-specific survival time of urachal adenocarcinoma patients was 45 months, which was significantly longer than that of bladder urothelial carcinoma patients with similar-stage disease (P = .047). Patients' cancer-specific survival was associated with tumor stage according to the Sheldon, Mayo, and TNM staging systems. In conclusion, urachal carcinomas are predominantly composed of invasive adenocarcinomas, which commonly demonstrate mucinous features. Most tumors present at advanced stages but are still associated with a better survival rate than bladder urothelial carcinomas.
    Human pathology 09/2015; 46(12). DOI:10.1016/j.humpath.2015.07.021 · 2.77 Impact Factor
  • Michael Markow · Marilyn M Bui · Hui-Yi Lin · Mark Lloyd · Wade J Sexton · Jasreman Dhillon ·
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    ABSTRACT: PAX8 is a transcription factor involved in the regulation of organogenesis of the thyroid gland, kidney, and Müllerian system. It is commonly expressed in epithelial tumors of thyroid and parathyroid glands, kidney, thymus, and female genital tract. PAX8 is increasingly used in the establishment of tissue of origin in carcinomas and has recently been identified in a subset of small blue round cell tumors including Ewing sarcomas/PNETs. However, it is unclear if this association in ES/PNETs is due to renal origin or is PNET specific. In this study we investigated the PAX8 staining pattern of primary renal and extra-renal ES/PNETs to explore its potential diagnostic and prognostic role. A tissue microarray (TMA) of 22 cases of extra-renal Ewing/PNETs and two separate cases of primary renal PNET whole slide sections were immunohistochemically stained with rabbit polyclonal PAX8 antibody. PAX8 was positive in 2 of 2 primary renal PNETs and in 14 (64 %) cases of the extra renal PNETs. The association between PAX8 immunoreactivity and Ewing/PNET was identified in both primary renal and extra-renal Ewing/PNETs for the first time. Further studies are warranted to verify these findings and to shed light in the tumorigenesis of Ewing/PNET. However, PAX8 is not useful in establishing a diagnosis of Ewing/PNET due to its presence in different tumors like carcinomas, lymphomas and sarcomas. PAX8 does not seem to have prognostic value.
    Pathology & Oncology Research 09/2015; DOI:10.1007/s12253-015-9986-8 · 1.86 Impact Factor
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    ABSTRACT: Accurate pathologic interpretation of testicular germ cell tumors (GCTs) can be problematic due to low incidence and variation in histologic patterns. By analyzing changes in the diagnosis of testicular specimens after secondary review, we hoped to determine how these can affect prognosis and treatment. From 1999 to 2013, a total of 235 patients underwent radical orchiectomy at a referring facility and had pathology specimens reanalyzed by our center's pathologists with expertise in genitourinary malignancies. We identified discrepancies in pathologic reporting. Fifty (21.3%) patients had variations in interpretation of their orchiectomy specimens. A clinically significant alteration was identified in 16 (6.8%) patients, most commonly due to recognition (or misrecognition) of lymphovascular invasion (LVI) associated with nonseminomatous germ cell tumors (NSGCTs). Changes in LVI status resulted in upstaging or downstaging from clinical stage 1A to stage 1B or vice versa in six patients with NSGCTs, with a subsequent change in therapeutic strategy. In addition, one patient with stage 1 pure seminoma had been misclassified with nonseminoma. Inaccurate interpretation of orchiectomy specimens is not uncommon and may lead to incorrect tumor staging, imprecise assignment of progression risk, and inappropriate management recommendations. Secondary opinions of primary GCT orchiectomy specimens potentially facilitate appropriate counseling and therapeutic strategies. Copyright© by the American Society for Clinical Pathology.
    American Journal of Clinical Pathology 08/2015; 144(2):289-94. DOI:10.1309/AJCPJTX8R6CVWSRW · 2.51 Impact Factor
  • Pranav Sharma · Jasreman Dhillon · Wade J. Sexton ·
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    ABSTRACT: Intratubular germ cell neoplasia (ITGCN) is a precursor lesion for testicular germ cell tumors, most of which are early stage. ITGCN is also associated with testicular cancer or ITGCN in the contralateral testis, leading to a risk of bilateral testicular malignancy. Testicular biopsy detects most cases, and orchiectomy is the treatment of choice in patients with unilateral ITGCN. Low-dose radiation therapy is recommended in patients with bilateral ITGCN or ITGCN in the solitary testis, but the long-term risks of infertility and hypogonadism need to be discussed with the patient. Rare histologies of primary testicular cancer are also discussed. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Clinics of North America 06/2015; 42(3). DOI:10.1016/j.ucl.2015.04.002 · 1.20 Impact Factor
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    ABSTRACT: We present a rare case of testicular extramedullary plasmacytoma (EMP) in a 43-year-old man with multiple myeloma and diffuse systemic involvement refractory to chemotherapy. Multiple myeloma is typically found within the bone marrow and rarely involves other organs and sites. EMPs are most frequently associated with the head and neck region, but in rare cases testicular involvement have been seen. These mimic other causes of testicular swelling and therefore require a full diagnostic workup and management similar to that of any scrotal pathology. Radical inguinal orchiectomy is the treatment of choice with the addition of adjunct or salvage radiation therapy if necessary. The prognosis with these lesions is poor and in cases of primary testicular plasmacytoma, progression to multiple myeloma is likely.
    04/2015; 9(3-4):240. DOI:10.5489/cuaj.2531
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    The Journal of Urology 04/2015; 193(4):e840. DOI:10.1016/j.juro.2015.02.2409 · 4.47 Impact Factor
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    ABSTRACT: The objective of this study was to determine if the percentage of sarcomatoid differentiation (%Sarc) in renal cell carcinoma (RCC) can be used for prognostic risk stratification, because sarcomatoid RCC (sRCC) is an aggressive variant of kidney cancer. We performed a retrospective analysis of patients who underwent surgery for RCC at our institution between 1999 and 2012. Pathology slides for all sRCC cases were reexamined by a single pathologist and %Sarc was calculated. %Sarc was analyzed as a continuous variable and as a categorical variable at cut points of 5%, 10%, and 25%. Potential prognostic factors associated with overall survival (OS) were determined using the Cox regression model. OS curves were generated using Kaplan-Meier methods and survival differences compared using the log-rank test. One thousand three hundred seven consecutive cases of RCC were identified, of which 59 patients had sRCC (4.5%). As a continuous variable %Sarc was inversely associated with OS (P = .023). Predictors of survival on multivariable analysis included pathologic (p) T status, tumor size, clinical (c) M status and %Sarc at the 25% level. OS was most dependent on the presence of metastatic disease (4 months vs. 21.2 months; P = .001). In cM0 patients with locally advanced (≥ pT3) tumors, OS was significantly diminished in patients with > 25 %Sarc (P = .045). However, %Sarc did not influence OS in patients with cM1 disease. Patients with sRCC have a poor overall outcome as evidenced by high rates of recurrence and death, indicating the need for more effective systemic therapies. In nonmetastatic patients, the incorporation of %Sarc in predictive nomograms might further improve risk stratification. Copyright © 2014 Elsevier Inc. All rights reserved.
    Clinical Genitourinary Cancer 12/2014; 191(4). DOI:10.1016/j.clgc.2014.12.001 · 2.32 Impact Factor
  • Yu Zhao · Marilyn M. Bui · Philippe E. Spiess · Jasreman Dhillon ·
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    ABSTRACT: Sclerosing perivascular epithelioid cell tumor (PEComa) is an unusual variant of PEComa that has a predilection for the retroperitoneum of middle-aged women. Sclerosing PEComas may also arise from the kidneys. This entity is a relatively indolent neoplasm for which surgery alone can be curative.
    Clinical Genitourinary Cancer 10/2014; 12(5). DOI:10.1016/j.clgc.2014.04.009 · 2.32 Impact Factor
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    ABSTRACT: Metastatic castrate resistant prostate cancer (mCRPC) is responsible for the majority of prostate cancer deaths with the median survival after diagnosis being 2 years. The metastatic lesions often arise in the skeleton, and current treatment options are primarily palliative. Using guidelines set forth by the National Comprehensive Cancer Network (NCCN), the medical oncologist has a number of choices available to treat the metastases. However, the sequence of those treatments is largely dependent on the patient history, treatment response and preferences. We posit that the utilization of personalized computational models and treatment optimization algorithms based on patient specific parameters could significantly enhance the oncologist's ability to choose an optimized sequence of available therapies to maximize overall survival. In this perspective, we used an integrated team approach involving clinicians, researchers, and mathematicians, to generate an example of how computational models and genetic algorithms can be utilized to predict the response of heterogeneous mCRPCs in bone to varying sequences of standard and targeted therapies. The refinement and evolution of these powerful models will be critical for extending the overall survival of men diagnosed with mCRPC.
    Clinical and Experimental Metastasis 08/2014; 31(8). DOI:10.1007/s10585-014-9674-1 · 3.49 Impact Factor
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    ABSTRACT: Objective To identify predictors of recurrence-free survival (RFS) based on the clinicopathological features of patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU) with bladder cuff resection. Materials and methods We retrospectively reviewed the records of patients from October 1998 to July 2012 at our tertiary institution and identified 120 patients with sufficient data who underwent RNU for UTUC. We recorded various clinical and histopathological parameters as potential predictors of outcome. Recurrence was defined as any occurrence of urothelial carcinoma after RNU either intravesically, local/regionally, or at distant sites. Univariate, multivariate, and RFS analyses were conducted using the Cox regression and Kaplan-Meier methods. Results The median age of our cohort was 71 years (interquartile range: 64–78). Median RNU-specimen tumor size was 3.0 cm (interquartile range: 2.0–5.0 cm). Fifty-four patients (45%) had a tumor<3.0 cm and 66 (55%) had a tumor≥3.0 cm. Eighty patients (66.7%) had organ-confined UTUC (≤pT2) and 40 (33.3%) had non–organ-confined UTUC (≥pT3). Sixty-five patients (54.2%) experienced at least 1 recurrence. Forty-three patients (35.8%) had at least 1 episode of intravesical recurrence and 28 (23.3%) had distant recurrence. A multivariate analysis revealed non–organ-confined disease (hazard ratio [HR] = 3.62, P<0.001), tumor diameter≥3 cm (HR = 1.97, P = 0.011), and male gender (HR = 1.81, P = 0.047) to be significant independent predictors of disease recurrence. The 5-year RFS rate was 46.9% and 25.8% for patients with tumor size<3 and≥3 cm, respectively. Conclusions Following RNU, the incidence of recurrence remains high among patients with UTUC. In our cohort of patients, tumor diameter≥3.0 cm, non–organ-confined UTUC, and male gender constitute important risk factors for poor RFS outcomes following RNU. These patients require diligent postoperative surveillance and may potentially benefit from perioperative systemic therapy.
    Urologic Oncology 07/2014; 32(5). DOI:10.1016/j.urolonc.2013.11.006 · 2.77 Impact Factor
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    ABSTRACT: Introduction: The importance of upper tract cytology for evaluating tumors is unclear. We correlated upper tract cytology with histologic findings in patients who underwent nephroureterectomy for upper tract urothelial carcinoma (UTUC) at a single tertiary care referral center. Materials and methods: 137 patients underwent nephroureterectomy between 2004 and 2012. 18 patients were excluded (benign tumors, atrophic kidneys with the remaining 119 patients serving as our study population). Upper tract cytology from the renal pelvis and/or ureter were retrospectively reviewed and analyzed with final pathology data in the remaining patients with UTUC. Results: 57% (68/119) had preoperative upper tract cytology collected. 73% (50/68) patients had abnormal cytology (positive, suspicious) with a sensitivity of 74% (which increased to 90% if atypical included), specificity of 50% and a positive predictive value of 98%. High grade tumors were more common than expected (77% high grade vs. 20% low grade). Abnormal cytology did not predict T stage or tumor grade. Interestingly, positive upper tract cytology was found in all of the UTUC CIS specimen. Conclusions: Upper tract cytology has been utilized to support the diagnosis of upper tract urothelial carcinoma. Our data demonstrates that abnormal cytology correlates well with the presence of disease but does not predict staging or grading in these respective patients.
    International braz j urol: official journal of the Brazilian Society of Urology 07/2014; 40(4):493-498. DOI:10.1590/S1677-5538.IBJU.2014.04.07 · 0.88 Impact Factor

  • The Journal of Urology 04/2014; 191(4):e510. DOI:10.1016/j.juro.2014.02.1434 · 4.47 Impact Factor

  • The Journal of Urology 04/2014; 191(4):e890. DOI:10.1016/j.juro.2014.02.2414 · 4.47 Impact Factor
  • Jasreman Dhillon · Sambit K Mohanty · Savitri Krishnamurthy ·
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    ABSTRACT: Thyroid-like follicular carcinoma of the kidney (TLFCK) is a recently described subtype of renal-cell carcinoma that is not currently included in the World Health Organization classification. Few sporadic case reports and one series have been reported with emphasis on histopathologic features. However, cytological features have not been described in the literature to date. A 34-year-old male presented with a renal mass. An intraoperative smear preparation of the tumor revealed a hypercellular smear with cells arranged in sheets without any follicular, papillary, or acinar arrangement. The most striking feature was the presence of acellular eosinophilic material associated with the neoplastic epithelial cells in the background of the smear. Individual tumor cells were oval, round, and plasmacytoid with mild nuclear pleomorphism, finely stippled nuclear chromatin, and inconspicuous nucleoli with moderate amount of eosinophilic cytoplasm and rare nuclear grooves. It was unclear at the time of the intraoperative assessment of the smear if the acellular eosinophilic material represented metachromatic matrix-like extracellular material, mucin, colloid, amyloid, or hyaline material. The differential diagnoses included a primary renal-cell carcinoma versus a metastatic tumor. Subsequent histopathologic examination was diagnostic of a rare, recently described primary neoplasm of the kidney called TLFCK. This work is a retrospective evaluation of the cytological features of TLFCK. It is important for cytopathologists to be aware of this entity and its cytological features to render a correct diagnosis for adequate management of these patients. Diagn. Cytopathol. 2012;. © 2012 Wiley Periodicals, Inc.
    Diagnostic Cytopathology 03/2014; 42(3). DOI:10.1002/dc.22930 · 1.12 Impact Factor
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    ABSTRACT: Congenital renal anomalies (CRAs) detected in adults include horseshoe kidney (HK), crossed renal ectopia, and malrotation. Congenital renal anomalies are rare, and renal lesions associated with CRA are rarer. Thirteen patients (11 men and 2 women) were referred to our center with renal masses in the context of CRAs, which included HK (10 cases), crossed renal ectopia (2 cases), and a pelvic kidney (1 case). The mean age at diagnosis was 60 years (37-76 years). All patients were treated with open surgery; 10, partial nephrectomies; 4, radical nephrectomies; and 1, nephroureterectomy with division of the renal isthmus. Pathology ranged from benign (simple cortical cysts, chronic pyelonephritis with secondary hydronephrosis) to malignant (12 cases of renal cell carcinomas [RCCs] and 1 case of urothelial carcinoma). Two patients of HKs presented with bilateral renal masses. The size of the RCC ranged from 2.5 to 13 cm. There were 11 cases of clear cell RCC, 1 case of papillary RCC (type 1), and 1 case of urothelial carcinoma. All the cases of RCC had negative surgical margins. Follow-up available in all patients ranged from 1 month up to 49 months. None of the patients developed any locoregional recurrences or distant metastases. In this patient cohort, the most common congenital anomaly associated with RCC is HK. All tumors behaved in an indolent fashion with prognosis related to pathologic tumor stage. Partial nephrectomy is a safe and effective procedure in appropriately selected patients.
    Annals of diagnostic pathology 02/2014; 18(1):14-7. DOI:10.1016/j.anndiagpath.2013.10.002 · 1.12 Impact Factor
  • Zibadi S · Sexton WJ · Bui MM · Dhillon J ·

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    ABSTRACT: The cytology literature relating to diagnostic accuracy using whole slide imaging is scarce. We studied the diagnostic concordance between glass and digital slides among diagnosticians with different profiles to assess the readiness of adopting digital cytology in routine practice. This cohort consisted of 22 de-identified previously screened and diagnosed cases, including non-gynecological and gynecological slides using standard preparations. Glass slides were digitalized using Aperio ScanScope XT (×20 and ×40). Cytopathologists with (3) and without (3) digital experience, cytotechnologists (4) and senior pathology residents (2) diagnosed the digital slides independently first and recorded the results. Glass slides were read and recorded separately 1-3 days later. Accuracy of diagnosis, time to diagnosis and diagnostician's profile were analyzed. Among 22 case pairs and four study groups, correct diagnosis (93% vs. 86%) was established using glass versus digital slides. Both methods more (>95%) accurately diagnosed positive cases than negatives. Cytopathologists with no digital experience were the most accurate in digital diagnosis, even the senior members. Cytotechnologists had the fastest diagnosis time (3 min/digital vs. 1.7 min/glass), but not the best accuracy. Digital time was 1.5 min longer than glass-slide time/per case for cytopathologists and cytotechnologists. Senior pathology residents were slower and less accurate with both methods. Cytopathologists with digital experience ranked 2(nd) fastest in time, yet last in accuracy for digital slides. There was good overall diagnostic agreement between the digital whole-slide images and glass slides. Although glass slide diagnosis was more accurate and faster, the results of technologists and pathologists with no digital cytology experience suggest that solid diagnostic ability is a strong indicator for readiness of digital adoption.
    10/2013; 4(1):28. DOI:10.4103/2153-3539.120727
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    ABSTRACT: The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. The overexpression of ASNS was validated by analyzing other public CRPC data sets. ASNS protein expression, as detected by reverse-phase protein lysate array, was tightly correlated with gene copy number. In addition, ASNS protein expression, as determined by IHC analysis, was associated with progression to a therapy-resistant disease state in TMAs that included 77 castration-resistant and 40 untreated prostate cancer patient samples. Knockdown of ASNS by small-interfering RNAs in asparagine-deprived media led to growth inhibition in both androgen-responsive (ie, LNCaP) and castration-resistant (ie, C4-2B) prostate cancer cell lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30). Together, our results suggest that ASNS is up-regulated in cases of CRPC and that depletion of asparagine using ASNS inhibitors will be a novel strategy for targeting CRPC cells.
    American Journal Of Pathology 03/2012; 180(3):895-903. DOI:10.1016/j.ajpath.2011.11.030 · 4.59 Impact Factor
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    ABSTRACT: The recently described transcriptomic switch to a mitosis program in castration-resistant prostate cancer (CRPC) suggests that mitotic proteins may be rationally targeted at this lethal stage of the disease. In this study, we showed upregulation of the mitosis-phase at the protein level in our cohort of 51 clinical CRPC cases and found centrosomal aberrations to also occur preferentially in CRPC compared with untreated, high Gleason-grade hormone-sensitive prostate cancer (P<0.0001). Expression profiling of chemotherapy-resistant CRPC samples (n = 25) was performed, and the results were compared with data from primary chemotherapy-naïve CRPC (n = 10) and hormone-sensitive prostate cancer cases (n = 108). Our results showed enrichment of mitosis-phase genes and pathways, with progression to both castration-resistant and chemotherapy-resistant disease. The mitotic centromere-associated kinesin (MCAK) was identified as a novel mitosis-phase target in prostate cancer that was overexpressed in multiple CRPC gene-expression datasets. We found concordant gene expression of MCAK between our parent and murine CRPC xenograft pairs and increased MCAK protein expression with clinical progression of prostate cancer to a castration-resistant disease stage. Knockdown of MCAK arrested the growth of prostate cancer cells suggesting its utility as a potential therapeutic target.
    PLoS ONE 02/2012; 7(2):e31259. DOI:10.1371/journal.pone.0031259 · 3.23 Impact Factor

Publication Stats

62 Citations
49.13 Total Impact Points


  • 2014-2015
    • Moffitt Cancer Center
      • Department of Biostatistics
      Tampa, Florida, United States
    • University of South Florida
      Tampa, Florida, United States
  • 2010-2012
    • University of Texas MD Anderson Cancer Center
      • Department of Pathology
      Houston, Texas, United States