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1.
J Pers Med ; 14(4)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38673021

RESUMEN

The pathologic diagnosis of pleural mesothelioma is generally based on international guidelines, but no compulsory points based on different drugs approvals in different European countries are required to be reported. According to the last (2021) edition of the World Health Organization classification of pleural tumors, the nuclear grade of epithelioid-type mesothelioma should be always inserted in the pathologic report, while the presence of BRCA-associated protein-1 (BAP1) (clone C4) loss and a statement on the presence of the sarcomatoid/nonepithelioid component are fundamental for both a screening of patients with suspected BAP1 tumor predisposition syndrome and the eligibility to perform first-line immunotherapy at least in some countries. Several Italian experts on pleural mesothelioma who are deeply involved in national scientific societies or dedicated working groups supported by patient associations agreed that the pathology report of mesothelioma of the pleura should always include the nuclear grade in the epithelioid histology, which is an overt statement on the presence of sarcomatoid components (at least 1%, in agreement with the last classification of pleural mesothelioma) and the presence of BAP1 loss (BAP1-deficient mesothelioma) or not (BAP1-retained mesothelioma) in order to screen patients possibly harboring BAP1 tumor predisposition syndrome. This review aims to summarize the most recent data on these three important elements to provide evidence regarding the possible precision needs for mesothelioma.

2.
Oncol Ther ; 12(1): 73-95, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38200361

RESUMEN

INTRODUCTION: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. METHODS: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. RESULTS: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. CONCLUSIONS: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

3.
J Clin Med ; 12(20)2023 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-37892804

RESUMEN

Background: In the metastatic setting, cancer patients may not benefit from standard care regimes and their diseases undergo drug resistance due to tumour cell heterogeneity and genomic landscape complexity. In recent years, there have been several attempts to personalise the diagnostic-therapeutic path and to propose novel strategies based on not only histological test results but also on each patient's clinical history and molecular biology. Profiling molecular tests allows physicians to investigate the single tumour genomic landscape and to promote targeted approaches. The Molecular Tumour Board (MTB) is a multidisciplinary committee dedicated to selecting individualised and targeted therapeutic strategies appropriate for patients suffering from diseases that present resistance to standard care. Materials and Methods: Our MTB settled in "Azienda Ospedaliero Universitaria delle Marche", Ancona (AN), Italy, and includes oncologists, molecular biologists, geneticists, and other specialists. Clinical cases are referred by physicians to the MTB, through the Cancer and Research Centre of the Marche Region (CORM), through a telemedicine platform. Four possible molecular profiles are available: FoundationOne® CDx e FoundationOne®Liquid CDx and two local Next Generation Sequencing (NGS) panels, with 16 DNA genes and 10 RNA genes respectively. The resulting genetic mutations and their analyses are evaluated by all the members of the Board and a report for each patient is provided with medical recommendations. Results: from June 2021 to May 2023, we collected data from 97 referral patients (M: 49, F: 48). The mean age was 60.6 years (range 22-83 years). 90 cases were approved for testing. Only seven patients were not eligible for genomic profiling. In two patients who were eligible, molecular profiling was not performed because a tissue sample was not available. Off-label therapy was recommended for three patients. 5% of cases (5/88) showed addressable driver mutations associated with an existing targeted therapy and were immediately enrolled. Conclusions: MTB presents a powerful tool for offering precise medical goals. Our Department of Clinical Oncology also takes advantage of the important role of multidisciplinary teams, through the establishment of CORM and MTB meetings, within which there is the chance to perform NGS-based analyses. It will be important in the future to implement the use of genomic profiling to improve personalised care and to guide the choice of suitable therapies and more appropriate management of patients.

4.
Diagnostics (Basel) ; 13(14)2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37510137

RESUMEN

Echobronchoscope-guided transbronchial needle aspiration (EBUS-TBNA) is mainly used as the transbronchial approach to hilar/mediastinal lymph nodes or lesions, for diagnostic or staging purposes. Moreover, the role of linear EBUS-TBNA as a diagnostic tool for central intrapulmonary lesions adjacent to the trachea or the major bronchi is also well established. However, since the tip of the ultrasound probe at the distal end of the echobronchoscope is very thin, it can be wedged through smaller peripheral bronchi, reaching the distal parenchyma and allowing for peripheral pulmonary lesion sampling. The main aim of this retrospective study was to evaluate the diagnostic yield and the safety of EBUS-TBNA in the diagnosis of pulmonary peripheral nodules. The database of the Interventional Pulmonology Unit of Azienda Ospedaliero-Universitaria delle Marche (Ancona, Italy) was evaluated to identify peripheral pulmonary nodules approached by EBUS-TBNA. Thirty patients with a single peripheral pulmonary nodule located peripherally to the subsegmental bronchi of the lower lobes and adjacent to a small bronchus greater than 3 mm in diameter were included in this study. The nodule was visible using endoscopic ultrasound in 28 patients and the diagnosis was obtained via EBUS-TBNA in 26 cases (12 adenocarcinoma, 5 typical carcinoid tumors, 4 hamartoma and 5 metastatic lesions). The diagnostic yield was 86.6% for all 30 patients and 92.8% if only the 28 patients in which the lesion was visualized via echobronchoscopy were considered. No relevant adverse events were observed. We conclude that EBUS-TBNA may be an effective and safe option to sample pulmonary peripheral nodules in selected patients with lower lobe peripheral pulmonary lesions adjacent to small bronchi greater than 3 mm in diameter and reachable with the EBUS-TBNA probe.

5.
Adv Respir Med ; 91(1): 1-8, 2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36648877

RESUMEN

INTRODUCTION: The role of EBUS-TBNA in the diagnosis and staging of lung cancer is well established. EBUS-TBNA can be performed using different aspiration techniques. The most common aspiration technique is known as "suction". One alternative to the suction technique is the slow-pull capillary aspiration. To the best of our knowledge, no studies have assessed the diagnostic yield of slow-pull capillary EBUS-TBNA in PD-L1 amplification assessment in NSCLC. Herein, we conducted a single-centre retrospective study to establish the diagnostic yield of slow-pull capillary EBUS-TBNA in terms of PD-L1 in patients with NSCLC and hilar/mediastinal lymphadenopathies subsequent to NSCLC. MATERIALS AND METHODS: Patients with hilar and/or mediastinal lymph node (LN) NSCLC metastasis, diagnosed by EBUS-TBNA between January 2021 and April 2022 at Pulmonology Unit of "Ospedali Riuniti di Ancona" (Ancona, Italy) were enrolled. We evaluated patient characteristics, including demographic information, CT scan/ FDG-PET features and final histological diagnoses, including PD-L1 assessment. RESULTS: A total of 174 patients underwent EBUS-TBNA for diagnosis of hilar/mediastinal lymphadenopathies between January 2021 and April 2022 in the Interventional Pulmonology Unit of the "Ospedali Riuniti di Ancona". Slow-pull capillary aspiration was adopted in 60 patients (34.5%), and in 30/60 patients (50.0%) NSCLC was diagnosed. EBUS-TBNA with slow-pull capillary aspiration provided adequate sampling for molecular biology and PD-L1 testing in 96.7% of patients (29/30); in 15/29 (51.7%) samples with more than 1000 viable cells/HPF were identified, whereas in 14/29 (48.3%) samples contained 101-1000 viable cells/HPF. CONCLUSION: These retrospective study shows that slow-pull capillary aspiration carries an excellent diagnostic accuracy, almost equal to that one reported in literature, supporting its use in EBUS-TBNA for PD-L1 testing in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Linfadenopatía , Humanos , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Metástasis Linfática/diagnóstico por imagen , Estudios Retrospectivos
6.
Diagnostics (Basel) ; 12(11)2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36428837

RESUMEN

Rapid on-site evaluation (ROSE) is a procedure that allows immediate assessment of adequacy of cytological specimens obtained by fine needle aspiration (FNA). The application of ROSE diagnostic categories has been applied in various organs, but not in thoracic pathology. We aimed to retrospectively assess the concordance with the final diagnosis of a categorization from C1 (inadequate) to C5 (neoplastic) during ROSE performed with bronchoscopic or percutaneous sampling procedures of thoracic lesions in a large series of consecutive cases. This retrospective single-center study evaluated 2282 consecutive ROSEs performed on 1827 patients from January 2016 to December 2020 in 994 cases of transbronchial needle aspiration (TBNA) in peripheral pulmonary lesions, in 898 transthoracic FNAs, in 318 ultrasound-guided TBNAs, in 50 conventional TBNAs and in 22 endobronchial TBNAs. False positive and false negative cases of ROSE were 43 (1.88%) and 73 (3.2%), respectively, when compared with the definitive diagnosis. The sensitivity, specificity and the positive and negative prognostic values of ROSE were 94.84%, 95.05%, 96.89% and 91.87%, respectively. Overall concordance between ROSE and the final diagnosis was 0.8960 (Cohen's kappa). No significant differences were observed in terms of sampling procedures and type and location of the lesions. A tiered classification scheme of ROSE from C1 to C5 during bronchoscopic and percutaneous sampling procedures is helpful in effectively guiding clinical management of patients with thoracic lesions.

7.
Front Med (Lausanne) ; 9: 1087028, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36714142

RESUMEN

Background: Transbronchial needle aspiration (TBNA) is a sampling tool that has demonstrated a higher accuracy in the diagnosis of peripheral pulmonary lesions (PPL) compared to other techniques. However, there are no studies investigating the value of TBNA in defining the genotype of peripheral lung cancer. Objective: To evaluate the accuracy of TBNA in defining the molecular characteristics of peripheral lung cancer. Methods: Consecutive patients who underwent TBNA for the diagnosis of a PPL at the Pulmonary Unit of the Azienda Ospedali Riuniti of Ancona (Italy) between January 2020 and September 2022 were included in the study. TBNA was performed under fluoroscopic guidance and the additional support of an ultrasound miniprobe, with an ultrathin bronchoscope with a flexible 21G needle. Samples were smeared on glass slides for cytological evaluation and flushed in 10% neutral-buffered formalin for cell-blocks. Results: 154 patients were enrolled:55 were diagnosed with adenocarcinoma and 21 with squamous cell carcinoma. TBNA correctly diagnosed 43/55 (78.2%) patients with adenocarcinoma and 17/21 (81.0%) patients with squamous cell carcinoma, with a sensitivity of 77.5%. Complete genotyping for guiding targeted therapies was obtained in 52 patients (86.6%). Conclusions: TBNA is a valid tool for the diagnosis of PPL, allowing a correct diagnosis and a complete genotyping of the tumors in a considerable proportion of patients.

8.
Case Rep Dermatol ; 13(3): 502-505, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34899232

RESUMEN

Nodular cutaneous amyloidosis represents the rarest variant of primary localized cutaneous amyloidosis. The proposed management ranges from topical or systemic agents to surgical treatment. Complete surgical excision is advisable due to its potential progression to systemic amyloidosis due to dermis and subcutaneous tissue infiltration. However, in particular locations, the risk of functional complications is high, so an alternative treatment option should be considered. We report a case of a large primary nodular cutaneous amyloidosis of the leg involving the joint capsule which was successfully treated by incomplete surgical removal, without recurrences at 7-year follow-up.

9.
J Thorac Dis ; 13(10): 5741-5751, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34795923

RESUMEN

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of cases and miR-31 seems to be involved in BAP1 regulation at post-transcriptional level. The aim of this study was to evaluate the interaction between BAP1 and miR-31 in MPM and their prognostic role in MPM. METHODS: The expression of BAP1 and miR-31 was analyzed in tissues of 55 MPM patients treated with first-line chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and Log-rank test was used to investigate differences among subgroups. Multivariate Cox regression analysis was used to evaluate independent predictors of survival. RESULTS: In the whole cohort, loss of BAP1 was associated with a significant improvement in OS, but not in PFS. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS (P=0.028), but not with OS (P=0.059). By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels (median OS 22.6 vs. 17.0 months, P=0.017 and median PFS 8.7 vs. 5.1 months, P=0.020). The BAP1 and miR-31 combination was confirmed at multivariate analysis as an independent prognostic factor for e-MPM patients. CONCLUSIONS: In this preliminary study, we found that the prognostic stratification of e-MPM patients may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors characterized by BAP1 retained and high miR-31 levels with worse clinical outcome.

10.
Lung Cancer ; 146: 318-326, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32622302

RESUMEN

INTRODUCTION: The prognostic role of BRCA1 associated protein-1 (BAP1) expression in malignant pleural mesothelioma (MPM) is a matter of debate. We aimed to clarify whether MPM patients with loss of BAP1 expression have better overall survival (OS) compared to BAP1 positive patients. METHODS: BAP1 immunohistochemical staining of tumor samples from 60 MPM patients treated at our institution with first-line chemotherapy was evaluated. A systematic literature search was also performed. Only cohort studies that investigated BAP1 by immunohistochemistry (IHC) and reported hazard ratio (HR) values for OS obtained through multivariate analysis (or adjusted for histotype) were considered. A dataset comprising 638 MPM patients was added to our cohort and included in the meta-analysis. RESULTS: In our cohort, 23 samples (38 %) were BAP1 positive/retained (≥1 %) and 37 samples (62 %) were BAP1 negative/loss. BAP1 loss was associated with epithelioid histotype (p 0.01). Median OS times were 14.8 months (95 % CI: 10.7-29.3) and 18.1 months (95 % CI: 11.2-25.8) for negative and positive BAP1 expression, respectively (p 0.2). At multivariate analysis, again no differences were observed among the two groups (p 0.81). Similarly, the meta-analysis consisting of 698 patients showed no difference in terms of OS according to BAP1 status (HR 1.11; 95 % CI, 0·76-1·61; p 0.60). CONCLUSIONS: BAP1 expression is not an independent prognostic factor for MPM patients and it should not be considered without taking into account tumor histotype. Future studies should investigate its predictive role in patients treated with new emerging therapies such as immunotherapy.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Biomarcadores de Tumor , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Pronóstico , Proteínas Supresoras de Tumor , Ubiquitina Tiolesterasa
11.
Radiol Med ; 125(1): 24-30, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31531810

RESUMEN

PURPOSE: The increasing number of computed tomography (CT) performed allows the more frequent identification of small, solid pulmonary nodules or ground-glass opacities. Video-assisted thoracic surgery (VATS) represents the standard in most lung resections. However, since VATS limit is the digital palpation of the lung parenchyma, many techniques of nodule localization were developed. The aim of this study was to determine the feasibility and safety of CT-guided microcoil insertion followed by uniportal VATS wedge resection (WR). MATERIALS AND METHODS: Retrospective study in a single institution, including patients undergone CT-guided microcoil insertion prior to uniportal VATS resection between May 2015 and December 2018. The lesion was identified using fluoroscopy. RESULTS: Forty-six consecutive patients were enrolled (22 male and 24 female). On CT: 5 cases of GGO, 2 cases of semisolid nodules, 39 cases of solid nodules. The median pathologic tumor size was 1.21 cm. Neither conversion to thoracotomy nor microcoil dislodgement was recorded. All patients underwent uniportal VATS WR (9/46 underwent completion lobectomy after frozen section). WR median time was 105 min (range 50-150 min). No patients required intraoperative re-resection for positive margins. After radiological procedure, 1 case of hematoma and 2 cases of pneumothorax were recorded. Four complications occurred in the postoperative period. The mean duration of chest drain and length of stay were 2.9 and 4.6 days, respectively. CONCLUSIONS: CT-guided microcoil insertion followed by uniportal VATS resection was a safe and feasible procedure having a minimal associated complications rate and offering surgeons the ease of localization of small intrapulmonary nodules.


Asunto(s)
Marcadores Fiduciales , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugía , Radiografía Intervencional/métodos , Cirugía Torácica Asistida por Video , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Hematoma/etiología , Humanos , Masculino , Persona de Mediana Edad , Nódulos Pulmonares Múltiples/patología , Tempo Operativo , Neumotórax/etiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/efectos adversos , Adulto Joven
12.
Lung Cancer (Auckl) ; 8: 45-55, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28740441

RESUMEN

ROS1 rearrangement characterizes a small subset (1%-2%) of non-small cell lung cancer and is associated with slight/never smoking patients and adenocarcinoma histology. Identification of ROS1 rearrangement is mandatory to permit targeted therapy with specific inhibitors, demonstrating a significantly better survival when compared with conventional chemotherapy. Detection of ROS1 rearrangement is based on in situ (immunohistochemistry, fluorescence in situ hybridization) and extractive non-in situ assays. While fluorescence in situ hybridization still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of ROS1 with some gene fusion partner. On the other hand, immunohistochemistry is the most cost-effective screening technique, but it seems to be characterized by low specificity. Extractive molecular assays are expensive and laborious methods, but they specifically recognize almost all ROS1 fusions using a limited amount of mRNA even from formalin-fixed, paraffin-embedded tumor tissues. This review is a discussion on the present and futuristic diagnostic scenario of ROS1 identification in lung cancer.

14.
Anal Quant Cytopathol Histpathol ; 35(4): 189-96, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24341121

RESUMEN

IgG4-related sclerosing disease, a multiorgan system disease that has been identified in the last 10 years, is a fibroinflammatory condition with a marked propensity to manifest itself as mass forming lesions characterized by three main histological features (sclerosis, obliterative phlebitis and lymphoplasmacytic infiltrate) and by the presence of abundant IgG4+ plasma cells, frequent elevation of serum IgG4 and a dramatic initial response to steroid therapy. The aim of this mini-review is to increase the capacity to identify the characteristic features of IgG4-related sclerosing disease in specific organs and in two newly proposed entities (urethral caruncle and paratesticular fibrous pseudotumor) using biopsy specimens and methods of counting IgG4. In addition we examine the relationship between IgG4-related sclerosing disease and malignancy. In fact, an increased ability to recognize the characteristic features of IgG4-related sclerosing disease would play an extremely important role in avoiding unnecessary surgery in favor of initiating corticosteroid therapy.


Asunto(s)
Glucocorticoides/uso terapéutico , Granuloma de Células Plasmáticas , Inmunoglobulina G/inmunología , Neoplasias , Flebitis , Diagnóstico Diferencial , Errores Diagnósticos , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/tratamiento farmacológico , Granuloma de Células Plasmáticas/inmunología , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Flebitis/diagnóstico , Flebitis/tratamiento farmacológico , Flebitis/inmunología , Esclerosis/diagnóstico , Esclerosis/tratamiento farmacológico , Esclerosis/inmunología
15.
Cell Oncol (Dordr) ; 36(1): 37-42, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23132460

RESUMEN

BACKGROUND: Prostate tumour overexpressed 1, PTOV1, was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer (PCa). It has been suggested that overexpression of PTOV1 can contribute to the proliferative status of prostate tumour cells and thus to their biological behaviour. METHODS: PTOV1 and Ki67 were immunohistochemically evaluated in PCa, atypical adenomatous hyperplasia (AAH), high-grade prostatic intraepithelial neoplasia (HGPIN), and normal-looking epithelium (NEp) of the transition zone (TZ) in 40 radical prostatectomies with pT2a Gleason score 6 PCa (20 with AAH and 20 with HGPIN) and in 10 simple prostatectomies (SPs) (5 with AAH and 5 with HGPIN). The aim was to evaluate PTOV1 protein expression as a marker for tumor development and progression from AAH to PCa. RESULTS: The proportions of PTOV1 and Ki67 positive cells increased from NEp through AAH and HGPIN to PCa. In particular, the mean Hscore of PTOV1 expression in AAH was 110.90, i.e., close to three times that of NEp (40.76), similar to that of HGPIN (105.61) and lower than that of PCa (137.03). The mean values in AAH and HGPIN associated with cancer in the RPs were slightly higher than in the SPs. CONCLUSION: Our findings related to PTOV1 expression in AAH, similar to those in HGPIN, provide additional evidence linking AAH to prostatic adenocarcinoma.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Epitelio/metabolismo , Proteínas de Neoplasias/biosíntesis , Próstata/metabolismo , Neoplasia Intraepitelial Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anciano , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Epitelio/patología , Humanos , Hiperplasia , Inmunohistoquímica/métodos , Antígeno Ki-67/biosíntesis , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Próstata/patología , Prostatectomía , Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/patología , Reproducibilidad de los Resultados
17.
Hum Pathol ; 42(12): 1931-6, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21676431

RESUMEN

Prostate tumor overexpressed 1 was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer. It has been suggested that overexpression of prostate tumor overexpressed 1 can contribute to the proliferative status of prostate tumor cells and, thus, to their biologic behavior. Prostate tumor overexpressed 1 and Ki-67 were immunohistochemically evaluated in prostate cancer, high-grade prostatic intraepithelial neoplasia, and normal-looking epithelium in 20 cystoprostatectomies and 20 radical prostatectomies with pT2a Gleason score 6 prostate cancer. The aim was to see whether there were differences in marker expression between cystoprostatectomies and radical prostatectomies. The proportions of prostate tumor overexpressed 1- and Ki-67-positive cells in the cystoprostatectomies and radical prostatectomies increased from normal-looking epithelium through high-grade prostatic intraepithelial neoplasia, away from and adjacent to prostate cancer, to prostate cancer. Prostate tumor overexpressed 1 expression in prostate cancer in cystoprostatectomies was lower than in radical prostatectomies, the differences being significant; there were significant differences in Ki-67 indices. In conclusion, our findings related to prostate tumor overexpressed 1 expression in high-grade prostatic intraepithelial neoplasia, evaluated adjacent and away from prostate cancer, and in incidental and clinical cancers give further support to the concept of field effect in prostatic carcinogenesis as well as to differences in the process of prostatic carcinogenesis between cystoprostatectomies and radical prostatectomies.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Antígeno Ki-67/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Proliferación Celular , Cistectomía , Epitelio/metabolismo , Epitelio/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Hallazgos Incidentales , Antígeno Ki-67/genética , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Proteínas de Neoplasias/genética , Próstata/metabolismo , Próstata/patología , Prostatectomía , Neoplasia Intraepitelial Prostática/cirugía , Neoplasias de la Próstata/cirugía , Vesículas Seminales/patología , Vesículas Seminales/cirugía
18.
Histopathology ; 57(4): 572-9, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20955382

RESUMEN

AIMS: To investigate prostate stem cell antigen (PSCA) and Ki-67 expression in normal-looking epithelium (NEp), atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma (PCa). METHODS AND RESULTS: PSCA and Ki-67 were evaluated immunohistochemically in NEp, atrophy, HGPIN and PCa in 20 radical prostatectomies (RPs) and 20 cystoprostatectomies (CyPs). The proportions of PSCA positive cells and of cases with PSCA expression increased from NEp through atrophy and HGPIN to PCa. The differences between NEp and HGPIN and PCa and between atrophy and HGPIN and PCa were statistically significant for the away and adjacent locations, in both the RP and CyP groups. The differences between HGPIN and PCa were statistically significant in the RP group when it was away from PCa and in the CyP group when it was adjacent to and away from PCa. The values in the RPs were slightly greater than in the CyPs, the differences being not statistically significant. The proportions of Ki-67 positive nuclei increased from atrophy and NEp to HGPIN and PCa. The correlation between the proportion of Ki-67 positive nuclei and that of PSCA-positive cells was statistically significant. CONCLUSIONS: PSCA expression, deregulated in atrophy and HGPIN, is a marker associated with neoplastic transformation of prostate cells, both in RPs and CyPs.


Asunto(s)
Adenocarcinoma/metabolismo , Antígenos de Neoplasias/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neoplasia Intraepitelial Prostática/metabolismo , Neoplasias de la Próstata/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Biomarcadores de Tumor/análisis , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Proteínas Ligadas a GPI/biosíntesis , Humanos , Inmunohistoquímica , Antígeno Ki-67/biosíntesis , Masculino , Persona de Mediana Edad , Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/patología
20.
Urology ; 74(2): 385-90, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19501882

RESUMEN

OBJECTIVES: To ascertain which variables of bladder urothelial carcinoma (UC) might be useful in predicting either UC involving the prostate (UCP) or incidental prostate adenocarcinoma in radical cystoprostatectomy specimens. METHODS: The bladder and whole-mount prostate sections of 248 radical cystoprostatectomy specimens were reviewed. Stepwise discriminant analysis was used to predict UCP or incidental prostate adenocarcinoma. RESULTS: UCP was present in 94 patients (37.9%). UC originated from the prostatic urethra and periurethral ducts in 78 (31.45%), and isolated direct extension of UC from the bladder was present in 16 patients (6.45%). The periurethral ducts coexisted with direct extension of bladder UC in 11 patients (4.4%). Prostate adenocarcinoma was identified in 123 patients (49.6%). Carcinoma in situ and high-grade urothelial papillary carcinoma were seen in 8 (3.2%) and 5 (2.0%) patients, respectively. In 57 (23%), 64 (25.8%), and 87 (35.1%) patients, UC had invaded the subepithelial connective tissue, muscularis propria, and perivesical tissue, respectively. UC was multifocal in 53 patients (21.4%). The tumor was in the trigone and bladder neck in 160 patients (64.5%). Of the 248 patients, 98 (39.5%) had a history of recurrence. Stepwise discriminant analysis selected 3 variables of bladder UC (previous recurrence and location and number of foci) and correctly predicted the group in 72.2% of patients without and with UCP. Discriminant analysis selected 2 variables of bladder UC (focality and previous recurrence) and correctly predicted the group in 57.7% of patients without and with prostate adenocarcinoma. CONCLUSIONS: Our approach can identify bladder UC variables that could guide urologists in the selection of the most appropriate surgical procedure.


Asunto(s)
Carcinoma de Células Transicionales/cirugía , Cistectomía , Prostatectomía , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Vejiga Urinaria/cirugía , Adenocarcinoma/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patología , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias de la Vejiga Urinaria/patología
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