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CONTEXT.: Core biopsies are standard of care for diagnosis and surveillance of prostate cancer. Fragmentation makes numeric assessment of cancer challenging and increases risk of inaccurate staging with direct implications on management. OBJECTIVE.: To determine factors responsible for fragmentation at our institution. DESIGN.: Prostate core biopsies performed at 2 hospital sites during 1 week were prospectively identified. Biopsies were received in multipart formalin jars, either mounted on a nonadherent dressing pad (Telfa, Medtronic Inc) or freely suspended, and grossed by experienced pathologists' assistants. Fragmentation was defined as the difference between number of cores sent by the clinician and number of cores counted by the pathologist on microscopy. RESULTS.: Forty-six cases (15 benign; 31 malignant) with 535 specimen jars were identified of which 309 of 535 (57.8%) had >1 biopsy core per jar; 230 of 535 (43%) were received mounted on Telfa and 185 of 535 (34.6%) had histologic evidence of adenocarcinoma. Overall fragmentation rate was 157 of 535 (29.3%). Lowest fragmentation rate was seen when 1 core was submitted per jar regardless of mounting method (31 of 226; 14% for single versus 126 of 309; 41% for >1 per jar; P < .001). For 1 Telfa-mounted core, rate of fragmentation was 5 of 18 (27.8%) versus 26 of 203 (12.8%) when unmounted (P = .24). Significant increase in fragmentation of Telfa-mounted cores was seen when there were 3 per jar (32 of 70; 46% mounted fragmented versus 9 of 47; 19% unmounted fragmented specimens; P = .01). CONCLUSIONS.: Submission of >1 biopsy core per jar and use of Telfa for mounting are associated with increased fragmentation. We recommend limiting submission to 1 core per jar and avoid mounting on Telfa pads.
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Brain metastases can occur in nearly half of patients with early and locally advanced (stage I-III) non-small cell lung cancer (NSCLC). There are no reliable histopathologic or molecular means to identify those who are likely to develop brain metastases. We sought to determine if deep learning (DL) could be applied to routine H&E-stained primary tumor tissue sections from stage I-III NSCLC patients to predict the development of brain metastasis. Diagnostic slides from 158 patients with stage I-III NSCLC followed for at least 5 years for the development of brain metastases (Met+, 65 patients) versus no progression (Met-, 93 patients) were subjected to whole-slide imaging. Three separate iterations were performed by first selecting 118 cases (45 Met+, 73 Met-) to train and validate the DL algorithm, while 40 separate cases (20 Met+, 20 Met-) were used as the test set. The DL algorithm results were compared to a blinded review by four expert pathologists. The DL-based algorithm was able to distinguish the eventual development of brain metastases with an accuracy of 87% (p < 0.0001) compared with an average of 57.3% by the four pathologists and appears to be particularly useful in predicting brain metastases in stage I patients. The DL algorithm appears to focus on a complex set of histologic features. DL-based algorithms using routine H&E-stained slides may identify patients who are likely to develop brain metastases from those who will remain disease free over extended (>5 year) follow-up and may thus be spared systemic therapy. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Algoritmos , PatologistasRESUMO
The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays.
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Ácidos Nucleicos Livres , Vesículas Extracelulares , Células Neoplásicas Circulantes , Humanos , Biópsia Líquida , Ácidos Nucleicos Livres/genética , Biomarcadores , Células Neoplásicas Circulantes/patologiaRESUMO
Liquid biopsy, through isolation and analysis of disease-specific analytes, has evolved as a promising tool for safe and minimally invasive diagnosis and monitoring of tumors. It also has tremendous utility as a companion diagnostic allowing detection of biomarkers in a range of cancers (lung, breast, colon, ovarian, brain). However, clinical implementation and validation remains a challenge. Among other stages of development, preanalytical variables are critical in influencing the downstream cellular and molecular analysis of different analytes. Although considerable progress has been made to address these challenges, a comprehensive assessment of the impact on diagnostic parameters and consensus on standardized and optimized protocols is still lacking. Here, we summarize and critically evaluate key variables in the preanalytical stage, including study population selection, choice of biofluid, sample handling and collection, processing, and storage. There is an unmet need to develop and implement comprehensive preanalytical guidelines on the optimal practices and methodologies.
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Neoplasias , Humanos , Neoplasias/diagnóstico , Biópsia Líquida , BiomarcadoresRESUMO
PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P < .001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45% , respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P < .001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%) . The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.
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Circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) from whole blood are emerging as important biomarkers that potentially aid in cancer diagnosis and prognosis. The microfilter technology provides an efficient capture platform for them but is confounded by two challenges. First, uneven microfilter surfaces makes it hard for commercial scanners to obtain images with all cells in-focus. Second, current analysis is labor-intensive with long turnaround time and user-to-user variability. Here we addressed the first challenge through developing a customized imaging system and data pre-processing algorithms. Utilizing cultured cancer and CAF cells captured by microfilters, we showed that images from our custom system are 99.3% in-focus compared to 89.9% from a top-of-the-line commercial scanner. Then we developed a deep-learning-based method to automatically identify tumor cells serving to mimic CTC (mCTC) and CAFs. Our deep learning method achieved precision and recall of 94% (± 0.2%) and 96% (± 0.2%) for mCTC detection, and 93% (± 1.7%) and 84% (± 3.1%) for CAF detection, significantly better than a conventional computer vision method, whose numbers are 92% (± 0.2%) and 78% (± 0.3%) for mCTC and 58% (± 3.9%) and 56% (± 3.5%) for CAF. Our custom imaging system combined with deep learning cell identification method represents an important advance on CTC and CAF analysis.
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Fibroblastos Associados a Câncer , Aprendizado Profundo , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Fibroblastos Associados a Câncer/patologia , Biomarcadores , Prognóstico , Linhagem Celular TumoralRESUMO
Context: Cytology is the study of whole cells in diagnostic pathology. Unlike standard histologic thinly sliced specimens, cytologic preparations consist of preparations of whole cells where cells commonly cluster and aggregate. As such, cytology preparations are generally much thicker than histologic slides, resulting in large patches of defocus when examined under the microscope. A diagnostic aggregate of cells often cannot be viewed in focus together, requiring pathologists to continually manipulate the focal plane, complicating the task of accurately assessing the entire cellular aggregate and thus in making a diagnosis. Further, it is extremely difficult to acquire useful uniformly in-focus digital images of cytology preparations for applications such as remote diagnostic evaluations and artificial intelligence models. The predominant current method to address this issue is to acquire digital images at multiple focal planes of the entire slide, which demands long scanning time, complex and expensive scanning systems, and huge storage capacity. Aims: Here we report a unique imaging method that can acquire cytologic images efficiently and computationally render all-in-focus digital images that are highly compact. Methods and material: This method applies a metric-based digital refocusing to microscopy data collected with a Fourier ptychographic microscope (FPM). The digitally refocused patches of images are then synthesized into an all-in-focus image. Results: We report all-in-focus FPM results of thyroid fine needle aspiration (FNA) cytology samples, demonstrating our method's ability to overcome the height variance of 30⯵m caused by cell aggregation, and rendering images at high resolution (corresponds to a standard microscope with objective NA of 0.75) and that are all-in-focus. Conclusions: This technology is applicable to standard microscopes, and we believe can have an impact on diagnostic accuracy as well as ease and speed of diagnosing challenging specimens. While we focus on cytology slides here, we anticipate this technology's advantages will translate well for histology applications. This technique also addresses the issue of remote rapid evaluation of cytology preparations. Finally, we believe that by resolving the focus heterogeneity issues in standard digital images, this technique is a critical advance for applying machine learning to cytology specimens.
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Circulating tumor cells (CTCs) have been recognized as a major contributor to distant metastasis. Their unique role as metastatic seeds renders them a potential marker in the circulation for early cancer diagnosis and prognosis as well as monitoring of therapeutic response. In the past decade, researchers mainly focused on the development of isolation techniques for improving the recovery rate and purity of CTCs. These developed techniques have significantly increased the detection sensitivity and enumeration accuracy of CTCs. Currently, significant efforts have been made toward comprehensive molecular characterization, ex vivo expansion of CTCs, and understanding the interactions between CTCs and their associated cells (e.g., immune cells and stromal cells) in the circulation. In this review, we briefly summarize existing CTC isolation technologies and specifically focus on advances in downstream analysis of CTCs and their potential applications in precision medicine. We also discuss the current challenges and future opportunities in their clinical utilization.
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PURPOSE: We evaluated the prognostic value of 10 putative tumor markers by immunohistochemistry in a large multi-institutional cohort of patients with locally advanced urothelial cancer of the bladder (UCB) with the aim to validate their clinical value and to harmonize protocols for their evaluation. MATERIALS AND METHODS: Primary tumor specimens from 576 patients with pathologic (p)T3 UCB were collected from 24 institutions in North America and Europe. Three replicate 0.6-mm core diameter samples were collected for the construction of a tissue microarray (TMA). Immunohistochemistry (IHC) for 10 previously described tumor markers was performed and scored at 3 laboratories independently according to a standardized protocol. Associations between marker positivity and freedom from recurrence (FFR) or overall survival (OS) were analyzed separately for each individual laboratory using Cox regression analysis. RESULTS: The overall agreement of the IHC scoring among laboratories was poor. Correlation among the 3 laboratories varied across the 10 markers. There was generally a lack of association between the individual markers and FFR or OS. The number of altered cell cycle regulators (p53, Rb, and p21) was associated with increased risk of cancer recurrence (P < 0.032). There was no clear pattern in the relationship between the percentage of markers altered in an 8-marker panel and FFR or OS. CONCLUSIONS: This large international TMA of locally advanced (pT3) UCB suggests that altered expression of p53, Rb, and p21 is associated with worse outcome. However this study also highlights limitations in the reproducibility of IHC even in the most expert hands.
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Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/química , Carcinoma de Células de Transição/mortalidade , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Cooperação Internacional , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
Approximately 70% of advanced breast cancer patients will develop bone metastases, which accounts for â¼90% of cancer-related mortality. Breast cancer circulating tumor cells (CTCs) establish metastatic tumors in the bone after a close interaction with local bone marrow cells including pericytes and osteoblasts, both related to resident mesenchymal stem/stromal cells (BM-MSCs) progenitors. In vitro recapitulation of the critical cellular players of the bone microenvironment and infiltrating CTCs could provide new insights into their cross-talk during the metastatic cascade, helping in the development of novel therapeutic strategies. Human BM-MSCs were isolated and fractionated according to CD146 presence. CD146+ cells were utilized as pericyte-like cells (PLCs) given the high expression of the marker in perivascular cells, while CD146- cells were induced into an osteogenic phenotype generating osteoblast-like cells (OLCs). Transwell migration assays were performed to establish whether primary breast cancer cells (3384T) were attracted to OLC. Furthermore, proliferation of 3384T breast cancer cells was assessed in the presence of PLC- and OLC-derived conditioned media. Additionally, conditioned media cultures as well as transwell co-cultures of each OLCs and PLCs were performed with 3384T breast cancer cells for gene expression interrogation assessing their induced transcriptional changes with an emphasis on metastatic potential. PLC as well as their conditioned media increased motility and invasion potential of 3384T breast cancer cells, while OLC induced a dormant phenotype, downregulating invasiveness markers related with migration and proliferation. Altogether, these results indicate that PLC distinctively drive 3384T cancer cells to an invasive and migratory phenotype, while OLC induce a quiescence state, thus recapitulating the different phases of the in vivo bone metastatic process. These data show that phenotypic responses from metastasizing cancer cells are influenced by neighboring cells at the bone metastatic niche during the establishment of secondary metastatic tumors.
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Células da Medula Óssea/metabolismo , Neoplasias da Mama/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células Neoplásicas Circulantes/metabolismo , Osteoblastos/metabolismo , Pericitos/metabolismo , Células da Medula Óssea/patologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Meios de Cultivo Condicionados , Feminino , Humanos , Células-Tronco Mesenquimais/patologia , Células Neoplásicas Circulantes/patologia , Osteoblastos/patologia , Pericitos/patologiaRESUMO
The aim of this study was to assess the prognostic and predictive value of an untargeted assessment of tumor fractions in the plasma of metastatic breast cancer patients and to compare circulating tumor DNA (ctDNA) with circulating tumor cells (CTC) and conventional tumor markers. In metastatic breast cancer patients (n = 29), tumor fractions in plasma were assessed using the untargeted mFAST-SeqS method from 127 serial blood samples. Resulting z-scores for the ctDNA were compared to tumor fractions established with the recently published ichorCNA algorithm and associated with the clinical outcome. We observed a close correlation between mFAST-SeqS z-scores and ichorCNA ctDNA quantifications. Patients with mFAST-SeqS z-scores above three (34.5%) showed significantly worse overall survival (p = 0.014) and progression-free survival (p = 0.018) compared to patients with lower values. Elevated z-score values were clearly associated with radiologically proven progression. The baseline CTC count, carcinoembryonic antigen (CEA), and cancer antigen (CA)15-5 had no prognostic impact on the outcome of patients in the analyzed cohort. This proof of principle study demonstrates the prognostic impact of ctDNA levels detected with mFAST-SeqS as a very fast and cost-effective means to assess the ctDNA fraction without prior knowledge of the genetic landscape of the tumor. Furthermore, mFAST-SeqS-based ctDNA levels provided an early means of measuring treatment response.
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Circulating tumor cells (CTCs) play a central role in tumor dissemination and metastases, which are ultimately responsible for most cancer deaths. Technologies that allow for identification and enumeration of rare CTC from cancer patients' blood have already established CTC as an important clinical biomarker for cancer diagnosis and prognosis. Indeed, current efforts to robustly characterize CTC as well as the associated cells of the tumor microenvironment such as circulating cancer associated fibroblasts (cCAF), are poised to unmask key insights into the metastatic process. Ultimately, the clinical utility of CTC will be fully realized once CTC can be reliably cultured and proliferated as a biospecimen for precision management of cancer patients, and for discovery of novel therapeutics. In this review, we highlight the latest CTC capture and analyses technologies, and discuss in vitro strategies for culturing and propagating CTC.
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Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Animais , Biomarcadores Tumorais/metabolismo , Humanos , Neoplasias/metabolismo , Prognóstico , Microambiente Tumoral/fisiologiaRESUMO
Blood-based biomarkers such as circulating tumor cells (CTCs) provide dynamic real-time assessment of molecular tumor characteristics beyond the primary tumor. The aim of this study was to evaluate the feasibility of a size-based microfilter to assess multigene methylation analysis of enriched CTCs in a prospective proof-of principle study. We examined the quantitative methylation status of nine genes (AKR1B1, BMP6, CST6, HOXB4, HIST1H3C, ITIH5, NEUROD1, RASSF1, SOX17) in enriched CTCs from metastatic breast cancer patients. Feasibility and clinical performance testing were assessed in a test set consisting of 37 patients and 25 healthy controls. With established cut-off values from the healthy control group, methylation of enriched CTCs was detected in at least one gene in 18/37 patients (48.6%), while 97.8% of all control samples were unmethylated. Patients with CTCs unmethylated for CST6, ITIH5, or RASSF1 showed significantly longer PFS compared to patients with corresponding enriched methylated CTCs. This proof-of-principle study shows the feasibility of a size-based microfilter to enrich and analyze multigene methylation profile of CTCs from metastatic breast cancer patients. For the first time, we report that multigene methylation analysis of enriched CTCs provides prognostic information in metastatic breast cancer patients.
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OBJECTIVES: Despite successful surgery, 30-50% of patients with resectable non-small cell lung cancer develop tumor recurrence within 5 years of surgery. MATERIALS AND METHODS: In this prospective study, we performed CTC enumerations in 40 patients with non-metastatic lung adenocarcinoma (NMLA) using a size-based microfilter. Additionally, cfDNA isolated from plasma was analyzed in 35 out of 40 patients. RESULTS: CTCs were identified in 15 out of 40 patients (37.5%) with a range of 1-44 cells, whereas mutated cfDNA was only detected in 3 out of 35 patients (8.6%). Disease-free survival (DFS) was significantly associated with CTC positivity (log-rank p=0.025), grading (log-rank p=0.019), tumor stage (log-rank p=0.025) and lymph node status (log-rank p=0.029). Multivariate analysis, including tumor stage and grading, showed that CTC positivity (p=0.006), grading (0.039) and tumor stage (p=0.022) were independently associated with DFS. CONCLUSION: Our study found that microfilter-based CTC enumeration in NMLA patients is an independent predictor of worse DFS. The used NGS-based cfDNA characterization had limited sensitivity to be clinically informative in our study cohort. CTC assessment before surgery can thus identify NMLA patients at high risk of disease recurrence.
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Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/sangue , Células Neoplásicas Circulantes/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/patologia , Período Pré-Operatório , Prognóstico , Estudos ProspectivosRESUMO
Examining the hematogenous compartment for evidence of metastasis has increased significantly within the oncology research community in recent years, due to the development of technologies aimed at the enrichment of circulating tumor cells (CTCs), the subpopulation of primary tumor cells that gain access to the circulatory system and are responsible for colonization at distant sites. In contrast to other technologies, filtration-based CTC enrichment, which exploits differences in size between larger tumor cells and surrounding smaller, non-tumor blood cells, has the potential to improve CTC characterization through isolation of tumor cell populations with greater molecular heterogeneity. However, microscopic analysis of uneven filtration surfaces containing CTCs is laborious, time-consuming, and inconsistent, preventing widespread use of filtration-based enrichment technologies. Here, integrated with a microfiltration-based CTC and rare cell enrichment device we have previously described, we present a protocol for Fourier Ptychographic Microscopy (FPM), a method that, unlike many automated imaging platforms, produces high-speed, high-resolution images that can be digitally refocused, allowing users to observe objects of interest present on multiple focal planes within the same image frame. The development of a cost-effective and high-throughput CTC analysis system for filtration-based enrichment technologies could have profound clinical implications for improved CTC detection and analysis.
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Separação Celular/métodos , Diagnóstico por Imagem/métodos , Filtração/métodos , Microscopia/métodos , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Contagem de Células , Separação Celular/instrumentação , Tamanho Celular , Diagnóstico por Imagem/instrumentação , Desenho de Equipamento , Filtração/instrumentação , Humanos , Metástase Linfática , Microscopia/instrumentação , Neoplasias/sangue , Neoplasias/imunologia , Neoplasias/patologia , Células Neoplásicas Circulantes/imunologia , Células Neoplásicas Circulantes/metabolismo , Reologia , Análise de Célula Única/instrumentação , Análise de Célula Única/métodosRESUMO
Circulating tumor cells (CTCs) are shed from the primary tumor into the circulatory system and act as seeds that initiate cancer metastasis to distant sites. CTC enumeration has been shown to have a significant prognostic value as a surrogate marker in various cancers. The widespread clinical utility of CTC tests, however, is still limited due to the inherent rarity and heterogeneity of CTCs, which necessitate robust techniques for their efficient enrichment and detection. Significant recent advances have resulted in technologies with the ability to improve yield and purity of CTC enrichment as well as detection sensitivity. Current efforts are largely focused on the translation and standardization of assays to fully realize the clinical utility of CTCs. In this review, we aim to provide a comprehensive overview of CTC enrichment and detection techniques with an emphasis on novel approaches for rapid quantification of CTCs.
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Células Neoplásicas Circulantes/metabolismo , Biomarcadores Tumorais/análise , Técnicas Biossensoriais , Separação Celular/métodos , Técnicas Eletroquímicas , Humanos , Nanopartículas/química , Células Neoplásicas Circulantes/química , Análise Serial de TecidosRESUMO
OBJECTIVES: To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. RESULTS: Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). MATERIALS AND METHODS: We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. CONCLUSIONS: Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives' ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer.
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Negro ou Afro-Americano/estatística & dados numéricos , Disparidades em Assistência à Saúde , Hispânico ou Latino/estatística & dados numéricos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , População Branca/estatística & dados numéricos , Adulto , Idoso , Biomarcadores Tumorais/sangue , Índice de Massa Corporal , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/cirurgia , Curva ROC , Estudos Retrospectivos , Carga TumoralRESUMO
PURPOSE: We evaluated prostate specific antigen production by benign prostate tissue and Gleason score 3+3=6 (Grade Group 1) prostate cancer in black and white nonHispanic men. MATERIALS AND METHODS: We used Gleason score 3+3=6 (Grade Group 1) cases to assess prostate specific antigen production by benign prostate tissue in cases with low volume cancer that did not influence prostate specific antigen and in those with high volume cancer in which gland weight did not influence prostate specific antigen. We then created age, prostate specific antigen and prostate weight adjusted cohorts to demonstrate tumor volume per 1 ng/ml prostate specific antigen and 1 µg prostate specific antigen mass. Prostate specific antigen density and prostate specific antigen mass density were used to adjust for prostate weight. RESULTS: Comparison of 58 black and 301 white men with low volume cancer demonstrated equal prostate specific antigen production by benign prostate tissue. Comparison of 30 black and 75 white men with high volume cancer indicated that prostate specific antigen was being driven by cancer volume, with lower prostate specific antigen production in black men. In the cohort of 54 black and 134 white men matched by age, prostate specific antigen and prostate weight, tumor volume per 1 ng/ml prostate specific antigen or 1 µg prostate specific antigen mass adjusted for prostate weight was 25% and 26% higher in black men, respectively. CONCLUSIONS: Benign prostate tissue produces equal amounts of prostate specific antigen in black and white men. Gleason score 3+3=6 (Grade Group 1) prostate cancer produces less prostate specific antigen in black men. These data should be considered for lowering prostate specific antigen and its derivatives in determining biopsy thresholds and for adjusting values for active surveillance criteria in black men.
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Antígeno Prostático Específico/análise , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Biomarcadores Tumorais/análise , População Negra , Bases de Dados Factuais , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , População BrancaRESUMO
It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane's electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 µg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.