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Identification of new genetic risk factors for prostate cancer

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Asian Journal of Andrology 2009年第1期11卷 49-55页

作者： Michelle Guy Zsofia Kote-Jarai Graham G. Giles Ali Amin Al Olama Sarah K. Jugurnauth Shani Mulholland Daniel A. Leongamomlert Stephen M. Edwards Jonathan Morrison Helen I. Field Melissa C. Southey Gianluca Severi Jenny L. Donovan Freddie C. Hamdy David R Dearnaley Kenneth R. Muir Charmaine Smith Melisa Bagnato Audrey T. Ardern-Jones Amanda L. Hall Lynne T. O＇Brien Beatrice N. Gehr-Swain Rosemary A. Wilkinson angela cox Sarah Lewis Paul M. Brown Sameer G. Jhavar Malgorzata Tymrakiewicz Artitaya Lophatananon Sarah L. Bryant The UK Genetic Prostate Cancer Study Collaborators British Association of Urological Surgeons＇ Section of Oncology and The UK ProtecT Study Collaborators Alan Horwich Robert A. Huddart Vincent S. Khoo Christopher C. Parker Christopher J. Woodhouse Alan Thompson Tim Christmas Chris Ogden Cyril Fisher Charles Jameson Colin S. Cooper Dallas R. English John L. Hopper David E. Neal Douglas E Easton Rosalind A. Eeles Section of Cancer Genetics The Institute of Cancer Research Sutton Surrey SM2 5NG UK Cancer Epidemiology Centre The Cancer Council Victoria Carlton VIC 3053 Australia Centre for Molecular Environmental Genetic and Analytic Epidemiology The University of Melbourne Carlton VIC 3053 Australia Cancer Research UK Genetic Epidemiology Unit University of Cambridge Strangeways Laboratory Worts Causeway Cambridge CB1 8RN UK Department of Oncology University of Cambridge Strangeways Laboratory Worts Causeway Cambridge CB1 8RN UK Genetic Epidemiology Laboratory Department of Pathology The University of Melbourne Parkville VIC 3052 Australia Department of Social Medicine University of Bristol Bristol BS8 2PR UK Academic Urology Unit University of Sheffield Sheffield SIO 2JF UK The Royal Marsden NHS Foundation Trust Sutton Surrey SM2 5PT and London SW3 6JJ UK University of Nottingham Medical School Queens Medical Centre Nottingham NG7 2UH UK Institute for Cancer Studies University of Sheffield Sheffield SIO 2RX UK Surgical Oncology （Uro-Oncology S4） Departments of Oncology and Surgery University of Cambridge Addenbrooke＇s Hospital Cambridge CB2 2QQ UK A full list of authors is provided in the Supplementary Note online Ka Shing Centre Cambridge CB2 ORE UK Cancer Research UK Cambridge Research Institute Li Ka Shing Centre Cambridge CB2 ORE UK.

There is evidence that a substantial part of genetic predisposition to prostate cancer （PCa） may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.

关键词： prostate cancer genetics susceptibility loci SNPs relative risks

Land-walking ***-walking interventions in older adults:Effects on aerobic fitness

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Journal of Sport and Health Science 2020年第3期9卷 274-282页

作者： Andrew Haynes Louise H.Naylor Howard H.Carter angela L.Spence Elisa Robey Kay L.cox Barbara A.Maslen Nicola T.Lautenschlager Nicola D.Ridgers Daniel J.Green School of Human Sciences(Exercise and Sport Science) The University of Western AustraliaPerthWA 6009Australia School of Physiotherapy and Exercise Science Curtin UniversityPerthWA 6102Australia School of Medicine The University of Western AustraliaPerthWA 6009Australia Academic Unit for Psychiatry of Old Age Department of PsychiatryThe University of MelbourneMelbourneVIC 3010Australia North Western Mental Health Melbourne HealthMelbourneVIC 3010Australia Division of Psychiatry WA Centre for Health&AgeingThe University of Western AustraliaPerthWA 6009Australia Institute for Physical Activity and Nutrition(IPAN) School of Exercise and Nutrition SciencesDeakin UniversityGeelongVIC 3125Australia

Background:Low cardiorespiratory fitness is an independent predictor of all-cause and cardiovascular mortality,and interventions that increase fitness reduce ***-walking decreases musculoskeletal impact and risk of falls in older individuals,but it is unclear whether water-walking improves aerobic fitness in the same way as weight-dependent *** randomized controlled trial involved 3 intervention groups—a no-exercise control group(CG),a land-walking(LW)group,and a water-walking(WW)group—to investigate the comparative impacts of LWandWWto CG on ***:Both exercise groups attended individually tailored,center-based,intensity-matched 3×weekly sessions for 24 weeks,which progressed to 150 min of exercise per *** was followed by a 24-week no-intervention *** graded exercise tests were performed on a treadmill at Weeks 0,24,and ***:Maximal oxygen uptake increased from Week 0 to Week 24 in both exercise groups(0.57±0.62 mL/kg/min,0.03±0.04 L/min for LW;0.93±0.75 mL/kg/min,0.06±0.06 L/min for WW,mean±SE)compared to the CG(-1.75±0.78 mL/kg/min,-0.16±0.05 L/min)(group×time,p<0.05).Time to exhaustion increased significantly following LW only(123.4±25.5 s),which was significantly greater(p=0.001)than the CG(24.3±18.5 s).By Week 48,the training-induced adaptations in the exercise groups returned to near baseline ***:Our study supports current physical-activity recommendations that 150 min/week of moderate-intensity exercise produces improvements in fitness in previously sedentary older ***,LW andWW elicit similar improvements in fitness if conducted at the same relative ***-na?ve older individuals can benefit from the lower impact forces and decreased risk of falls associated withWWwithout compromising improvements in cardiorespiratory fitness.

关键词： Cardiorespiratory fitness Graded exercise test Physical activity Water exercise

Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

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World Journal of Gastroenterology 2016年第26期22卷 6065-6075页

作者： angela Lamarca Christina Rigby Mairéad G Mc Namara Richard A Hubner Juan W Valle Department of Medical Oncology The Christie NHS Foundation Trust Institute of Cancer Sciences University of Manchester Manchester Academic Health Science Centre

AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary ***: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing ***: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group).CONCLUSION: SREs are common and impact on patient’s morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/del

关键词： Advanced biliary tract cancer Pancreatic cancer Biliary obstruction Biliary stent Stent-related event

Renal-function change after transjugular intra-hepatic portosystemic shunt placement and its relationship with survival:a single-center experience

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Gastroenterology Report 2021年第4期9卷 306-312,I0001,I0002页

作者： Min Lang angela L.Lang Brian Q.Tsui Weiping Wang Brian K.Erly Bo Shen Baljendra Kapoor Department of Radiology Massachusetts General HospitalHarvard Medical SchoolBostonMAUSA Department of Anesthesia Critical Careand Pain ManagementMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Department of Radiology UCLA Medical CenterLos AngelesCAUSA Department of Radiology Mayo ClinicJacksonvilleFLUSA Colorado School of Public Health AuroraColoradoUSA The Inflammatory Bowel Disease Center at Columbia Columbia University Irving Medical CenterNew YorkNYUSA Division of Vascular and Interventional Radiology Imaging InstituteCleveland ClinicClevelandOHUSA

Background:The effect of transjugular intra-hepatic portosystemic shunt(TIPS)placement on renal function and the correlation of post-TIPS Cr with mortality remain *** study aimed to assess the effect of TIPS placement on renal function and to examine the relationship between post-TIPS Cr and mortality ***:A total of 593 patients who underwent de novo TIPS placement between 2004 and 2017 at a single institution were included in the *** pre-TIPS Cr level(T0;within 7 days before TIPS placement)and post-TIPS Cr levels,at 1–2 days(T1),5–12 days(T2),and 15–40 days(T3),were *** of Cr change after TIPS placement and the 1-year mortality rate were analysed using multivariable linear-regression and cox proportional-hazards models,***:Overall,21.4%of patients(n=127)had elevated baseline Cr(≤1.5 mg/dL;mean,2.5161.49 mg/dL)and 78.6%(n=466)had normal baseline Cr(<1.5 mg/dL;mean,0.9260.26 mg/dL).Patients with elevated pre-TIPS Cr demonstrated a decrease in post-TIPS Cr(difference,-0.60 mg/dL),whereas patients with normal baseline Cr exhibited no change(difference,<0.01 mg/dL).The 30-day,90-day,and 1-year mortality rates were 13%,20%,and 32%,*** bleeding as a TIPS-placement indication(hazard ratio=1.731;P=0.036),higher T0 Cr(hazard ratio=1.834;P=0.012),and higher T3 Cr(hazard ratio=3.524;P<0.001)were associated with higher 1-year mortality ***:TIPS placement improved renal function in patients with baseline renal dysfunction and the post-TIPS Cr level was a strong predictor of 1-year mortality risk.

关键词： TIPS transjugular intra-hepatic portosystemic shunt portal hypertension renal function renal failure mortality

Clinical implications of endogenous testosterone density on prostate cancer progression in patients with very favorable low and intermediate risk treated with radical prostatectomy

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Asian Journal of Andrology 2023年第5期25卷 556-563页

作者： Antonio Benito Porcaro Alessandro Tafuri Andrea Panunzio Clara Cerrato Alberto Bianchi Sebastian Gallina Stefano Vidiri Damiano D'Aietti Emanuele Serafin Giovanni Mazzucato Alessandro Princiotta Davide Brusa Matteo Brunelli Vincenzo Pagliarulo Maria angela Cerruto AlessandroAntonelli Department of Urology University of VeronaIntegrated University Hospital of VeronaVerona 37126Italy Department of Urology Vito Fazzi HospitalLecce 73100Italy Department of Pathology University of VeronaIntegrated University Hospital of VeronaVerona 37126Italy

We tested the association between endogenous testosterone density(ETD;the ratio between endogenous testosterone[ET]and prostate volume)and prostate cancer(PCa)aggressiveness in very favorable low-and intermediate-risk PCa patients who underwent radical prostatectomy(RP).Only patients with prostate-specific antigen(PSA)within 10 ng ml^(-1),clinical stage T1c,and International Society of Urological Pathology(IsUP)grade group 1 or 2 were *** ET levels up to 350 ng dl^(-1)were classified as *** quantitation density factors were evaluated as the ratio between percentage of biopsy-positive cores and prostate volume(biopsy-positive cores density,BPCD)and the ratio between percentage of cancer invasion at final pathology and prostate weight(tumor load density,TLD).Disease upgrading was coded as ISUP grade group>2,and progression as recurrence(biochemical and/or local and/or distant).Risk associations were evaluated by multivariable cox and logistic regression *** 320 patients,151(47.2%)had intermediate-risk ***(median:402.3 ng dl^(-1))resulted abnormal in 111(34.7%)cases(median ETD:9.8 ng dl^(-1)ml^(-1)).Upgrading and progression occurred in 109(34.1%)and 32(10.6%)cases,*** was predicted by ISUP grade group 2(hazard ratio[HR]:2.290;P=0.029)and upgrading(HR:3.098;P=0.003),which was associated with ISUP grade group 2(odds ratio[OR]:1.785;P=0.017)and TLD above the median(OR:2.261;P=0.001).After adjustment for PSAdensity and bodymass index(BMI),ETDabovethemedianwas positivelyassociatedwithBPCD(OR:3.404;P<0.001)and TLD(OR:5.238;P<0.001).Notably,subjects with abnormal ET were more likely to have higher BPCD(OR:5.566;P=0.002),as well as TLD(OR:14.998;P=0.016).Independently by routinely evaluated factors,as ETD increased,BPCD and TLD increased,but increments were higher for abnormal ET *** very favorable cohorts,ETD may further stratify the risk of aggressive PCa.

关键词： endogenous testosterone density prostate cancer radical prostatectomy tumor progression

Briganti’s 2012 nomogram is an independent predictor of prostate cancer progression in EAU intermediate-risk class:results from 527 patients treated with robotic surgery

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Asian Journal of Andrology 2024年第6期26卷 587-591页

作者： Antonio Benito Porcaro Francesca Montanaro Alberto Baielli Francesco Artoni Claudio Brancelli Sonia Costantino Andrea Franceschini Sebastian Gallina Alberto Bianchi Emanuele Serafin Alessandro Veccia Riccardo Rizzetto Matteo Brunelli Filippo Migliorini Salvatore Siracusano Maria angela Cerruto Riccardo Giuseppe Bertolo Alessandro Antonelli Department of Urology University of VeronaIntegrated University HospitalVerona 37126Italy Department of Pathology University of VeronaIntegrated University HospitalVerona 37126Italy Department of Life Health and Environmental SciencesUniversity of L’AquilaL’Aquila 67100Italy

The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti’s 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5–111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti’s 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060;95% CI: 1.021–1.100;P = 0.002);moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052;95% CI: 1.298–3.243;P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti’s 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist.

关键词： biochemical recurrence Briganti’s 2012 nomogram intermediate-risk prostate cancer pelvic lymph node invasion prostate cancer progression robot-assisted radical prostatectomy

Retrospective study on mixed neuroendocrine non-neuroendocrine neoplasms from five European centres

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World Journal of Gastroenterology 2019年第39期25卷 5991-6005页

作者： Melissa Frizziero Xin Wang Bipasha Chakrabarty Alexa Childs Tu V Luong Thomas Walter Mohid S Khan Meleri Morgan Adam Christian Mona Elshafie Tahir Shah Annamaria Minicozzi Wasat Mansoor Tim Meyer angela Lamarca Richard A Hubner Juan W Valle Mairéad G McNamara Department of Medical Oncology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Analytics and Development The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Pathology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Department of Medical Oncology Royal Free London NHS Foundation TrustLondon NW3 2QGUnited Kingdom UCL Cancer Institute University College LondonLondon WC1E 6AGUnited Kingdom Department of Histopathology Royal Free London NHS Foundation TrustLondon NW3 2QGUnited Kingdom Department of Gastroenterology and Medical Oncology Edouard Herriot HospitalHospices Civils de LyonLyon 69003France Department of Gastroenterology Cardiff and Vale University Health BoardUniversity Hospital of WalesCardiff CF14 4XWUnited Kingdom Department of Cellular Pathology Cardiff and Vale University Health BoardUniversity Hospital of WalesCardiff CF14 4XWUnited Kingdom Department of Pathology University Hospitals Birmingham NHS Foundation TrustBirmingham B15 2THUnited Kingdom Department of Hepatology University Hospitals Birmingham NHS Foundation TrustBirmingham B15 2THUnited Kingdom Department of Surgical Oncology The Christie NHS Foundation TrustManchester M20 4BXUnited Kingdom Division of Cancer Sciences University of ManchesterManchester M13 9PLUnited Kingdom

BACKGROUND Mixed neuroendocrine non-neuroendocrine neoplasm(MiNEN)is a rare diagnosis,mainly encountered in the gastro-entero-pancreatic *** is limited knowledge of its epidemiology,prognosis and biology,and the best management for affected patients is still to be *** To investigate clinical-pathological characteristics,treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of *** Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European *** data were retrospectively collected from medical *** samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of *** responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours ***-Meier analysis was applied to estimate survival *** between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions(univariate)and cox-regression analysis(multivariable).RESULTS Sixty-nine consecutive patients identified;Median age at diagnosis:64 ***:63.8%.Localised disease(curable):53.6%.Commonest sites of origin:colon-rectum(43.5%)and oesophagus/oesophagogastric junction(15.9%).The neuroendocrine component was;predominant in 58.6%,poorly differentiated in 86.3%,and large cell in 81.25%,of cases *** distant metastases analysed(73.4%)were occupied only by a poorly differentiated neuroendocrine ***-four percent of patients with localised disease underwent curative surgery;53%also received perioperative treatment,most often in line with protocols for adenocarcinomas from the same sites of *** was offered to most patients(68.1%)with advanced disease,and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal *** localised cases,median recurre

关键词： Mixed neuroendocrine non-neuroendocrine neoplasm 2017 World Health Organisation classification Mixed adeno-neuroendocrine carcinoma Gastro-enteropancreatic tract Digestive system Neuroendocrine neoplasms Survival outcomes

Prognostic importance of lymph node yield after curative resection of gastroenteropancreatic neuroendocrine tumours

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World Journal of Clinical Oncology 2020年第4期11卷 205-216页

作者： Jaseela Chiramel Rose Almond Astrid Slagter Adeel Khan Xin Wang Kok Haw Jonathan Lim Melissa Frizziero Bipasha Chakrabarty Annamaria Minicozzi angela Lamarca Wasat Mansoor Richard A Hubner Juan William Valle Mairéad Geraldine McNamara Department of Medical Oncology The Christie NHS Foundation TrustManchester M204BXUnited Kingdom Royal Free London NHS Foundation Trust London NW32QGUnited Kingdom Statistics Group Digital ServicesThe Christie NHS Foundation TrustManchesterM204BXUnited Kingdom Antoni van Leeuwenhoek/Netherlands Cancer Institute Amsterdam 1066 CxNetherlands Department of Pathology The Christie NHS Foundation TrustManchester M204BXUnited Kingdom Department of Surgery Barts Health NHS TrustLondon EC1A 7BEUnited Kingdom Division of Cancer Sciences University of ManchesterManchester M139PLUnited Kingdom

BACKGROUND The prognostic significance of lymph nodes(LNs)metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours(GEP NETs)undergoing curative resection is still *** studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy AIM To evaluate the effect of lymph node(LN)status and yield on relapse-free survival(RFS)and overall survival(OS)in patients with resected GEP *** Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed *** 3 tumours(Ki67>20%)were *** cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with *** A total of 217 patients were included in the *** median age was 59 years(21-97 years)and 51%(n=111)were *** tumour sites were small bowel(42%),pancreas(25%),appendix(18%),rectum(7%),colon(3%),gastric(2%),others(2%).Median follow up times for all patients were 41 mo(95%CI:36-51)and 71 mo(95%CI:63–76)for RFS and OS respectively;50 relapses and 35 deaths were *** were retrieved in 151 *** or more LNs were harvested in 106 patients and LN positivity reported in 114 *** or more positive LNs were detected in 62 *** result of univariate analysis suggested perineural invasion(P=0.0023),LN positivity(P=0.033),LN retrieval of≥8(P=0.047)and localisation(P=0.0049)have a statistically significant association with shorter RFS,but there was no effect of LN ratio on RFS:P=0.1 or OS:P=*** necrosis(P=0.021)and perineural invasion(P=0.016)were the only two variables significantly associated with worse *** the final multivariable analysis,localisation(pancreas HR=27.33,P=0.006,small bowel HR=32.44,P=0.005),and retrieval of≥8 LNs(HR=2.7,P

关键词： Well differentiated neuroendocrine tumours Pancreatic neuroendocrine tumours Small intestinal neuroendocrine tumours Ki67 Lymph node ratio Lymph node retrieval Lymph node positivity Relapse-free survival Overall survival

Expression of Multidrug Resistance ATP-Binding Cassette(ABC)Transporters in Canine Mammary Tumors

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Advances in Breast Cancer Research 2015年第3期4卷 77-85页

作者： Breno S.Salgado Suely Nonogaki Luisa M.Soares angela Akamatsu Cristiano R.N.da Silva Thiago P.Anacleto Rodolfo Malagó Rafael M.Rocha Fátima Gartner Noeme S.Rocha Departamento de Patologia Faculdade de Medicina de BotucatuUniversidade Estadual PaulistaCampus de BotucatuBotucatuBrazil Instituto de Ciências Biomédicas Abel Salazar Universidade do Porto(Intitute of Biomedical Sciences Abel Salazar of University of Porto)OportoPortugal Fundacao Antonio Prudente Hospital A.C.CamargoSao PauloBrazil Departamento de Clínica Veterinária Faculdade de Medicina Veterinária e ZootecniaUniversidade Estadual PaulistaUNESP.BotucatuBrazil Hospital Escola de Medicina Veterinária Fundacao de Ensino e Pesquisa de Itajubá—FEPIItajubáBrazil

Mammary neoplasms are the most common tumors in female dogs. They are usually treated using solely surgical mastectomy—which is recognized as unsatisfactory in many cases. Given this, the benefits of chemotherapy in dogs with mammary cancer need to be further explored. Some drugs that can be used for treating canines with mammary tumors may be substrates of uptake and/or efflux transporters such as the ATP-binding cassette (ABC) transporters. Unfortunately, very little is known regarding the pathobiology of such proteins in canine tumors, including mammary cancer. Accordingly, this study was designed to characterize the expression of ABC transporters P-glycoprotein, MRP1, and MRP2 and their relation with clinicopathologic factors in order to allow a better understanding of their influence in canine mammary cancer. P-glycoprotein was expressed in tumors from 55.8% of patients, while MRP1 and MRP2 were expressed in 37.2% and 39.5% of tumors, respectively. P-glycoprotein expression showed to be related with regional lymph node spread (P = 0.0038), as well as with tumor grade (P = 0.0353) and with a shorter survival (P = 0.0245). MRP1 revealed a strong association with a higher histological grade (P cox proportional-hazards regression multivariate analysis (P = 0.0216). No relations between MRP2 and clinicopathologic features were observed. We have found that P-glycoprotein and MRP1 are expressed in highly aggressive canine mammary tumors and are related with poor prognosis. Our results suggest that they may play a significant role in the course of canine mammary cancer progression and be promising candidate markers for a validation study on therapy outcome.

关键词： MDR1 P-Gp MRP1 MRP2 ABCC2 Mammary Neoplasms Prognosis Dog