Prostate biopsy histopathologic features correlate with a commercial gene expression assay's reclassification of patient NCCN risk category

The Prostate ◽  
2020 ◽  
Vol 80 (16) ◽  
pp. 1421-1428
Author(s):  
Nancy Y. Greenland ◽  
Janet E. Cowan ◽  
Emily Chan ◽  
Peter R. Carroll ◽  
Bradley A. Stohr ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Biopsy ◽  
Risk Category ◽  
Histopathologic Features

scholarly journals A urine-based Exosomal gene expression test stratifies risk of high-grade prostate Cancer in men with prior negative prostate biopsy undergoing repeat biopsy

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
James McKiernan ◽  
Mikkel Noerholm ◽  
Vasisht Tadigotla ◽  
Sonia Kumar ◽  
Phillipp Torkler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Prostate Biopsy ◽  
Repeat Biopsy ◽  
High Grade ◽  
Negative Prostate Biopsy

Molecular characteristics of renal cell carcinoma (RCC) risk groups from JAVELIN Renal 101.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 744-744 ◽  
Author(s):  
Toni K. Choueiri ◽  
John B. A. G. Haanen ◽  
James M. G. Larkin ◽  
Brian I. Rini ◽  
Laurence Albiges ◽  
...  
Keyword(s):  
Gene Expression ◽  
Objective Response ◽  
Homeobox Gene ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Response To Treatment ◽  
Molecular Characteristics ◽  
Risk Category ◽  
Cell Cycle Gene ◽  
Cd8 Cells

744 Background: The phase 3 JAVELIN Renal 101 trial in patients (pts) with advanced RCC demonstrated a progression-free survival (PFS) benefit and higher objective response rate (ORR) with avelumab + axitinib (A+Ax) vs sunitinib (S) (Motzer NEJM 2019). PFS and ORR favored A+Ax in all MSKCC risk groups, but median PFS varied. Here, we report results from analyses of baseline tumor samples to define molecular characteristics underlying risk group classifications. Methods: Nephrectomy or tumor samples from pts enrolled in the study were characterized by immunohistochemistry (CD8 and PD-L1), whole exome sequencing, or gene expression profiling (n = 705–850). Gene expression signatures (GES), pathway activation status, and mutational profiles were examined in relation to MSKCC risk groups. Results: Of the 886 total pts enrolled, 23%, 66%, and 11% had favorable (F), intermediate (I), or poor (P) MSKCC risk factors at baseline. In the F, I, and P groups, the ORR was 66%/38%, 50%/24%, and 31%/9%; median PFS was NR/16.7 mo, 13.3 mo/7.9 mo, and 5.6 mo/2.8 mo for the A+Ax/S arms, respectively. Neither the presence of PD-L1+ immune cells nor CD8+ cells differentiated the subgroups; however, the presence of PD-L1+ tumor cells was highest in the P group (p=0.0159). When compared to the I and P groups, the F group was enriched for NOTCH2 mutations (p=0.0002), displayed high FLT1 expression (p=0.007), and showed a trend favoring angiogenesis GES (JAVELIN Renal 101 and IMmotion150). The I group displayed few distinguishing characteristics (low neutrophil GES [p=0.02] and elevated homeobox gene expression [p=0.00052]). Relative to the F group, the P group showed higher cell cycle gene expression (p=0.0057) and PTEN mutation frequency, wild-type NOTCH2 genotype, elevated IMmotion150 Myeloid inflamed GES (p=0.0024), and macrophage-specific GES (p=0.0327), as well as GES for TH2 (p=0.0002), hypoxia (p=0.0199), glycolysis (p=0.0066), and the lowest expression of a dendritic cell GES (p=0.0209). Conclusions: In advanced RCC patients, biological differences within each MSKCC risk category may impact response to treatment and may help explain why these groups perform differently. Clinical trial information: NCT02684006.

ASSESSMENT OF METASTASIS-RELATED GENE EXPRESSION IN PROSTATE BIOPSY SPECIMENS

1999 ◽  
pp. 237
Author(s):  
Hiroki Kuniyasu ◽  
Patricia Troncoso ◽  
Keiji Inoue ◽  
Isaiah J. Fidler ◽  
Colin P. N. Dinney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Biopsy ◽  
Related Gene ◽  
Biopsy Specimens

scholarly journals  A Urine-Based Exosomal Gene Expression Test Stratifies Risk of High-Grade Prostate Cancer in Men with Prior Negative Prostate Biopsy Undergoing Repeat Biopsy

2020 ◽  
Author(s):  
James McKiernan ◽  
Mikkel Noerholm ◽  
Vasisht Tadigotla ◽  
Sonia Kumar ◽  
Phillipp Torkler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Clinical Features ◽  
Prostate Biopsy ◽  
Repeat Biopsy ◽  
Superior Performance ◽  
High Grade ◽  
Cut Point ◽  
Negative Biopsy ◽  
Initial Biopsy

Abstract BACKGROUND: Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate(IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established. Methods: As part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2-10ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results. Results: 229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35% and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.Conclusions: The EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2-10ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.

scholarly journals Comprehensive Association Analysis of 21-Gene Recurrence Score and Obesity in Chinese Breast Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiwei Tong ◽  
Weiqi Gao ◽  
Jiayi Wu ◽  
Siji Zhu ◽  
Ou Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Single Gene ◽  
Menopausal Status ◽  
Recurrence Score ◽  
Risk Category ◽  
Obese Patients ◽  
Breast Cancer Patients

PurposeA center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients.Patients and methodsLuminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status.ResultsAmong 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P=0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P<0.05). Compared to non-overweight patients, obese ones presented significantly higher ER, PR, CEGP1, Ki67, CCNB1 and GSTM1 (all P<0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P=0.001). RS was associated with DFS in non-overweight (P=0.046), but not in overweight (P=0.558) or obese (P=0.114) population.ConclusionsRS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.

scholarly journals Optimizing the Use of Gene Expression Profiling in Early-Stage Breast Cancer

2016 ◽  
Vol 34 (36) ◽  
pp. 4390-4397 ◽  
Author(s):  
Hyun-seok Kim ◽  
Christopher B. Umbricht ◽  
Peter B. Illei ◽  
Ashley Cimino-Mathews ◽  
Soonweng Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Decision Making ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Early Stage ◽  
Recurrence Score ◽  
Clinical Samples ◽  
Risk Category ◽  
Clinical Risk

Purpose Gene expression profiling assays are frequently used to guide adjuvant chemotherapy decisions in hormone receptor–positive, lymph node–negative breast cancer. We hypothesized that the clinical value of these new tools would be more fully realized when appropriately integrated with high-quality clinicopathologic data. Hence, we developed a model that uses routine pathologic parameters to estimate Oncotype DX recurrence score (ODX RS) and independently tested its ability to predict ODX RS in clinical samples. Patients and Methods We retrospectively reviewed ordered ODX RS and pathology reports from five institutions (n = 1,113) between 2006 and 2013. We used locally performed histopathologic markers (estrogen receptor, progesterone receptor, Ki-67, human epidermal growth factor receptor 2, and Elston grade) to develop models that predict RS-based risk categories. Ordering patterns at one site were evaluated under an integrated decision-making model incorporating clinical treatment guidelines, immunohistochemistry markers, and ODX. Final locked models were independently tested (n = 472). Results Distribution of RS was similar across sites and to reported clinical practice experience and stable over time. Histopathologic markers alone determined risk category with > 95% confidence in > 55% (616 of 1,113) of cases. Application of the integrated decision model to one site indicated that the frequency of testing would not have changed overall, although ordering patterns would have changed substantially with less testing of estimated clinical risk–high or clinical risk–low cases and more testing of clinical risk–intermediate cases. In the validation set, the model correctly predicted risk category in 52.5% (248 of 472). Conclusion The proposed model accurately predicts high- and low-risk RS categories (> 25 or ≤ 25) in a majority of cases. Integrating histopathologic and molecular information into the decision-making process allows refocusing the use of new molecular tools to cases with uncertain risk.

scholarly journals A Urine-Based Exosomal Gene Expression Test Stratifies Risk of High-Grade Prostate Cancer in Men with Prior Negative Prostate Biopsy Undergoing Repeat Biopsy

2020 ◽  
Author(s):  
James McKiernan ◽  
Mikkel Noerholm ◽  
Vasisht Tadigotla ◽  
Sonia Kumar ◽  
Phillipp Torkler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Clinical Features ◽  
Prostate Biopsy ◽  
Repeat Biopsy ◽  
Superior Performance ◽  
High Grade ◽  
Cut Point ◽  
Negative Biopsy ◽  
Initial Biopsy

Abstract BACKGROUND: Initial prostate biopsy often fails to identify prostate cancer resulting in patient anxiety, especially when clinical features such as prostate specific antigen (PSA) remain elevated, leading to the need for repeat biopsies. Prostate biomarker tests, such as the ExoDx™ Prostate(IntelliScore), or EPI test, have been shown to provide individualized risk assessment of clinically significant prostate cancer at initial biopsy; however, the performance in the repeat biopsy setting is not well established. Methods: As part of a previous prospective clinical validation study evaluating the performance of the EPI test, we collected first-catch, non-DRE urine samples across 22 sites from men with at least one prior negative biopsy scheduled to undergo a repeat prostate biopsy to rule out prostate cancer. All men were 50 years or older with a PSA 2-10ng/mL. Exosomal mRNA was extracted and expression of three genomic markers, PCA3, ERG and SPDEF was measured. The resulting EPI score was correlated with biopsy results. Results: 229 men with a prior negative biopsy underwent repeat biopsies. ExoDx Prostate demonstrated good performance ruling out high-grade (Grade group 2, GG2, or higher) prostate cancer (HGPCa) using the previously validated 15.6 cut point in the initial biopsy setting. The EPI test yielded an NPV of 92% independent of other clinical features and would have avoided 26% of unnecessary biopsies while missing only five patients with HGPCa (2.1%). Furthermore, the EPI test provided additional information at a cut-point of 20 and 29.6 with an NPV of 94%, potentially delaying 35% and 61% of unnecessary biopsies, respectively. AUC curves and Net Health Benefit Analyses demonstrated superior performance of ExoDx Prostate over PSA and clinical only risk calculators, i.e. ERSPC.Conclusions: The EPI test provided good performance using the 15.6 cut-point for ruling out HGPCa / GG2 or higher in men undergoing a repeat prostate biopsy with a PSA of 2-10ng/ml. Furthermore, the test utilizes gene expression data independent of clinical features to predict the likelihood of HGPCa / GG2 on a subsequent needle biopsy.

scholarly journals Integrative In Vivo Drug Testing Using Gene Expression Signature and Patient-Derived Xenografts from Treatment-Refractory HER2 Positive and Triple-Negative Subtypes of Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 574 ◽  
Author(s):  
Jin-Sun Ryu ◽  
Sung Hoon Sim ◽  
In Hae Park ◽  
Eun Gyeong Lee ◽  
Eun Sook Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Drug Testing ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Combined Treatment ◽  
Predictive Biomarkers ◽  
Pdx Models ◽  
Histopathologic Features

Patient-derived xenografts (PDXs) are powerful tools for translational cancer research. Here, we established PDX models from different molecular subtypes of breast cancer for in vivo drug tests and compared the histopathologic features of PDX model tumors with those of patient tumors. Predictive biomarkers were identified by gene expression analysis of PDX samples using Nanostring nCount cancer panels. Validation of predictive biomarkers for treatment response was conducted in established PDX models by in vivo drug testing. Twenty breast cancer PDX models were generated from different molecular subtypes (overall success rate, 17.5%; 3.6% for HR+/HER2−, 21.4% for HR+/HER2+, 21.9% for HR−/HER2+ and 22.5% for triple-negative breast cancer (TNBC)). The histopathologic features of original tumors were retained in the PDX models. We detected upregulated HIF1A, RAF1, AKT2 and VEGFA in TNBC cases and demonstrated the efficacy of combined treatment with sorafenib and everolimus or docetaxel and bevacizumab in each TNBC model. Additionally, we identified upregulated HIF1A in two cases of trastuzumab-exposed HR−/HER2+ PDX models and validated the efficacy of the HIF1A inhibitor, PX-478, alone or in combination with neratinib. Our results demonstrate that PDX models can be used as effective tools for predicting therapeutic markers and evaluating personalized treatment strategies in breast cancer patients with resistance to standard chemotherapy regimens.

scholarly journals Prolonged antibiotic therapy increases risk of infection after transrectal prostate biopsy: A case report after pancreasectomy and review of the literature

2014 ◽  
Vol 86 (4) ◽  
pp. 387 ◽  
Author(s):  
Guevar Maselli ◽  
Giacomo Tucci ◽  
Daniele Mazzaferro ◽  
Asim Ettamimi ◽  
Giulia Sbrollini ◽  
...  
Keyword(s):  
High Risk ◽  
Prostate Biopsy ◽  
Pancreatic Surgery ◽  
Infectious Complications ◽  
Major Surgery ◽  
Risk Category ◽  
Resistant Variant ◽  
High Risk Category ◽  
Transrectal Prostate Biopsy ◽  
History Of

Infection due to prostate biopsy afflicted more than 5% of patients and is the most common reason for hospitalization. A large series from US SEER-Medicare reported that men undergoing biopsy were 2.26 times more likely to be hospitalized for infectious complications within 30 days compared with randomly selected controls. The factors predicting a higher susceptibility to infection remain largely unknown but some authors have higlighted in the etiopathogenesis the importance of the augmented prevalence of ciprofloxacin resistant variant of bacteria in the rectum flora. We present one case of sepsis after transrectal prostate biopsy in a patient with history of pancreatic surgery. Based on our experience patients candidated to prostate biopsy with transrectal technique with history of recent major surgery represent an high risk category for infective complication. Also major pancreatic surgery should be consider an high risk category for infection. A transperineal approach and preventive measures (such as rectal swab) should be adopted to reduce biopsy driven infection.

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