RESUMO
This paper presents the largest study in Cyprus evaluating the frequency and distribution of BRCA1/2 mutations in a high risk patient cohort. Deleterious mutations in the BRCA1/2 genes were identified in 68 of the 527 patients tested (13%). It is of interest that a quarter of those tested positive, did not have an extensive family history of breast/ovarian cancer but were diagnosed with early onset breast cancer, ovarian cancer under the age of 60 or triple negative breast cancer. The spectrum of mutations identified in our patient cohort is different compared to other Mediterranean countries. Furthermore, several of the mutations detected are novel and have not been identified in other ethnic populations. This highlights the importance of operating a national reference center for cancer genetic diagnosis which offers services tailored to the needs of the Cypriot population.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Chipre/epidemiologia , Feminino , Predisposição Genética para Doença , Testes Genéticos , Genética Populacional , Humanos , Pessoa de Meia-Idade , Epidemiologia Molecular , Mutação , Neoplasias Ovarianas/epidemiologia , Neoplasias de Mama Triplo Negativas/epidemiologiaRESUMO
BACKGROUND: We sought to determine biomarker expression differences in head and neck squamous cell cancers (HNSCCs) based on p16/human papillomavirus (HPV) classification. In addition, our aim was to explore how expression of biomarkers is modulated after E6/E7 repression in HPV16⺠oropharyngeal cancer cells. METHODS: HPV16⺠and HPVâ» HNSCC cells were infected with retroviruses expressing short hairpin RNA targeting HPV16 E6/E7. Components of the epidermal growth factor receptor (EGFR) pathway before and after E6/E7 gene silencing were analyzed by immunoblotting and qRT-PCR. Protein expression of 13 biomarkers was analyzed using AQUA on a tissue microarray (TMA). The HPV16 status was determined using HPV16 in situ hybridization (ISH). RESULTS: In HPV16⺠cells, E6/E7 silencing was associated with PTEN upregulation and reduction of phosphorylated EGFR. Tumors were classified into four categories based on the HPV and p16 status. HPVâº/p16⺠tumors expressed significantly higher levels of E-cadherin (P = 0.003), PTEN (P = 0.004), lower levels of PI3Kp110 and ß-catenin (P = 0.07). There was a significant difference in overall survival (OS, P = 0.016) among the four subsets. The median OS was 24.83 months for p16â»/HPVâ» patients, 11.63 for p16â»/HPV⺠patients and was not reached for p16âº/HPVâ» and p16âº/HPV⺠groups. CONCLUSIONS: Aberrant EGFR signaling contributes to malignant conversion of HPV16⺠HNSCC cells. These results validate ß-catenin as a distinct biomarker in HPVâº/p16⺠HNSCC. Wnt signaling inhibitors merit exploration in HPVâº/p16⺠HNSCC.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Orofaríngeas/metabolismo , beta Catenina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Linhagem Celular Tumoral , Inibidor p16 de Quinase Dependente de Ciclina , Receptores ErbB/genética , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/virologia , PTEN Fosfo-Hidrolase/biossíntese , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Fosforilação , Interferência de RNA , RNA Interferente Pequeno , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína Supressora de Tumor p53/metabolismo , Via de Sinalização WntRESUMO
Barrett's esophagus (BE) is a major precursor factor of esophageal cancer (EC). The appropriate management of patients with BE depends on the presence or not of dysplasia and the type of dysplasia that occurs. Due to the small proportion of BE patients that progress to cancer, the value of surveillance programs are a matter of debate. On the contrary, in high risk group of patients surveillance programs have significant impact. Large prospective trials are needed to define the optimal management strategy. Elucidation of carcinogenesis' steps and signal transduction pathways could reveal potential biomarkers in the order of early prediction for a highly malignant neoplasm with dismal prognosis. An efficacious tailored-made manner focusing to the safety profile and associated costs should be practised for less severe disease. In this review a thorough investigation of all available methods dealing with the clinical management of BE is provided.
Assuntos
Esôfago de Barrett/complicações , Esôfago de Barrett/terapia , Neoplasias Esofágicas/etiologia , Ablação por Cateter , Criocirurgia , Humanos , Fotoquimioterapia , Fatores de RiscoRESUMO
BACKGROUND: Kallikreins, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. Here, we sought to determine the prognostic value of kallikrein 7 (hk7) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. PATIENTS AND METHODS: A tissue array composed of 150 advanced-stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel (Taxol) combination chemotherapy, was constructed. For evaluation of kallikrein 7 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). RESULTS: Mean follow-up time of the cohort was 34.35 months. One hundred and twenty eight of 150 cases had sufficient tissue for AQUA. In univariate survival analysis, low tumor hk7 expression was associated with better outcome for overall survival (OS) and disease-free survival in 3 years (P values 0.032 and 0.037, respectively). In multivariate survival analysis, adjusting for well-characterized prognostic variables, low tumor hk7 expression level was the most significant predictor variable for OS (95% confidence interval 0.125-0.729, P = 0.007). CONCLUSIONS: High tumor hk7 protein expression is associated with inferior patient outcome in ovarian cancer. hk7 may represent a promising prognostic factor in ovarian cancer.
Assuntos
Calicreínas/metabolismo , Neoplasias Ovarianas/metabolismo , Automação , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Imunofluorescência , Corantes Fluorescentes/metabolismo , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Indóis/metabolismo , Calicreínas/genética , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Fatores de Tempo , Análise Serial de TecidosRESUMO
BACKGROUND: The prognosis of patients with metastatic breast cancer and symptomatic bone marrow involvement is poor. The aim of treatment to these patients is palliation. In this study, we sought to determine the efficacy of therapy with low doses of capecitabine in this subgroup of patients. PATIENTS AND METHODS: Five consecutive breast cancer patients with overt bone marrow involvement were treated by low doses of capecitabine in our department. Four out of five patients also received bisphosphonates to palliate skeletal symptoms. The influence of this therapeutic regimen on tumor response, blood count normalization and overall survival was analysed. RESULTS: All patients except one responded in terms of their haematological profile within two months of the initiation of treatment. Duration of haematological response was 8+ months for all patients. In two of them, tumor response in other sites was evaluated as stable disease, in one as partial remission and in one as progressive disease. Two patients survived more than 22 months without bone marrow failure. CONCLUSION: These initial results are very encouraging for this subset of patients with poor prognosis and limited life expectancy. The administration of capecitabine might be an efficient alternative treatment option. Our results merit further investigation.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias da Medula Óssea/tratamento farmacológico , Neoplasias da Medula Óssea/secundário , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Idoso , Capecitabina , Desoxicitidina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
A small percentage (1-10%) of renal cell carcinomas (RCC) belongs to the sarcomatoid variant. These malignancies are aggressive with worse prognosis and unfortunately the results following immuno- and/or chemotherapy administration are discouraging. A 62-year-old Caucasian male with advanced renal cell cancer and sarcomatoid component treated with sunitinib is presented. Better understanding of prognostic and molecular markers might help the selection of patients with a chance of benefiting from administration of new targeted drugs.
Assuntos
Carcinoma de Células Renais/patologia , Diferenciação Celular , Neoplasias Renais/patologia , Sarcoma/patologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Evolução Fatal , Humanos , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pirróis/uso terapêutico , Sarcoma/tratamento farmacológico , SunitinibeRESUMO
PURPOSE: The extracellular domain (ECD) of the HER2 receptor is proposed as a real-time marker of HER2-positive breast cancer (BC). In this study, ECD-HER2 levels were compared with standard clinical and pathological prognostic factors. PATIENTS AND METHODS: In 247 consecutive patients (116 with early or localized BC, 116 with advanced or metastatic BC, and 16 with benign mastopathies), serum ECD-HER2 levels were measured. In 116 advanced-disease patients ECD-HER2 status was also studied by immunohistochemistry (IHC) and compared with established clinical and pathological variables. RESULTS: Mean serum ECD-HER2 value was 19.62 ng/ml (median 10.35, range 3-->250). Mean value in benign mastopathies was 9.04 ng/ml, 9.4 ng/ml in early disease and 34.5 ng/ml in advanced disease. No difference between benign mastopathies and early BC was observed, while significant difference between early and advanced BC (p<0.001) was noted. However, in advanced-disease patients a positive correlation of ECD-HER2 with IHC (p=0.002), disease grade (p=0.034) and level II axillary node involvement (p=0.011) was noted, as well as a significant negative correlation with estrogen receptor (ER) and progesterone receptor (PR) (p=0.035 and p=0.011, respectively). CONCLUSION: ECD-HER2 is a reliable marker for breast cancer, as suggested from the existing literature; therefore, its integration in the initial workup and follow-up routine of breast cancer, particularly the HER2-positive, is proposed.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Receptor ErbB-2/sangue , Doenças Mamárias/sangue , Doenças Mamárias/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/secundário , Membrana Celular/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Estadiamento de Neoplasias , Prognóstico , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
BACKGROUND: Despite progress achieved with new chemotherapeutic and endocrine agents, advanced breast cancer (ABC) remains a disease with poor prognosis. We sought to determine the efficacy of gemcitabine (GC) and oral vinorelbine (VB) in heavily preatreated ABC. PATIENTS AND METHODS: Patients previously treated with anthracyclines and taxanes in the metastatic setting with progressive disease were eligible. Treatment consisted of VB (60 mg/m2, orally) and GC (1000 mg/m2, intravenous infusion), every two weeks of a 28- day cycle. RESULTS: Thirty-one patients with ABC were enrolled. Toxicity was acceptable, mainly haematological. Three and 8 patients achieved a complete (9.6%) and partial (25.8%) response, respectively; ten patients (32.2%) had stable disease. Median time-to-progression was 5.3 months, while in responders 8.6 months. Median overall survival was 14 months. CONCLUSION: Oral VB and GC is an active and well-tolerated combination in anthracycline/taxane-pretreated ABC, representing an interesting option in this poor prognosis group of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia de Salvação , Administração Oral , Adulto , Idoso , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Taxoides/uso terapêutico , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
Adenocarcinomas account for 0.5-2% of all bladder cancers. Urachal carcinoma is a rare neoplasm which represents 0.01% of all cancers in adults and account for one third of bladder adenocarcinomas. A 65-year-old white man with an urachal mucinous adenocarcinoma is reported. None of the known predisposing risk factors for bladder cancer -such as tobacco use and professional exposure to chemicals -were identified in his past medical history. The patient suffered from multiple sclerosis for almost 11 years and in the last 6 years he was treated with low doses of mitoxantrone. He underwent a partial cystectomy and en block excision of the umbilical ligament and remains disease-free after one year. The development of this rare neoplasm should not be clearly dissociated from multiple sclerosis, either aetiologically sharing an unidentified common causative factor or due to its treatment with mitoxantrone.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/cirurgia , Úraco , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Cistectomia , Humanos , Masculino , Resultado do Tratamento , Úraco/cirurgiaRESUMO
In a continuously aging population, the burden of colorectal cancer (CRC) is rising among older patients. Despite the fact that almost half of the cases occur in patients over 75 years, this age group is subjected to disparities regarding diagnostic and therapeutic options. So far, exclusion of older patients from randomized clinical trials has resulted in a lack of evidence-based guidelines. Nevertheless, newer data from studies specifically targeting older patients and subgroup analyses indicate that proper treatment planning and specific medical and geriatric assessment can achieve a safe and beneficial treatment result in older patients, often with similar outcomes to their younger counterparts. Resection of the primary tumour, if feasible, should be the primary goal of surgery aiming for cure, although it should be avoided under emergency conditions. Chronological age per se should not be an exclusion criterion for adjuvant or palliative chemotherapy, or targeted therapies. Careful patient selection, dose adjustments, close monitoring and early intervention in the event of side effects are essential. The benefits of treatment must be balanced with potential effects of treatment and patients' wishes.
RESUMO
Adenocarcinoma of the pancreas carries a uniformly poor prognosis with high rates of loco-regional as well as systemic recurrence. Outcomes remain poor, even for early stage and resectable disease. It is perceived as inherently resistant to most of the currently available treatment options. Evidence supports the need for adjuvant chemotherapy but controversy remains in relation to the use of combined therapy, novel agents and the most appropriate timing of therapy. Despite no clear consensus, mainstay of treatment following resection is based primarily on single agent gemcitabine. Promising new agents and molecules of prognostic as well as predictive value under evaluation offer intriguing data, despite issues surrounding adjuvant therapy strategies. In this article, we sought to review the different therapeutic adjuvant modalities and future directions.
Assuntos
Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Neoplasias Pancreáticas/terapia , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante , Humanos , Imunoterapia , Terapia de Alvo Molecular , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoAssuntos
Benzenossulfonatos/administração & dosagem , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Sarcoma de Kaposi/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Esquema de Medicação , Seguimentos , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Sarcoma de Kaposi/secundário , Neoplasias Cutâneas/secundário , Sorafenibe , Resultado do TratamentoAssuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Neovascularização Patológica/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Distúrbios da Voz/induzido quimicamente , Bevacizumab , Feminino , Humanos , Pessoa de Meia-Idade , Neovascularização Patológica/complicações , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/complicações , Ovário/irrigação sanguínea , Ovário/efeitos dos fármacos , Prega Vocal/irrigação sanguínea , Prega Vocal/efeitos dos fármacos , Prega Vocal/patologia , Distúrbios da Voz/complicações , Distúrbios da Voz/patologiaRESUMO
BACKGROUND: p53 protein is regarded as a valuable prognostic marker in cancer with a potential use as a molecular target. Here, we sought to determine the prognostic value of p53 in ovarian cancer using a novel method of compartmentalized in situ protein analysis. PATIENTS AND METHODS: A tissue array composed of 141 advanced stage ovarian cancers uniformly treated was constructed. For evaluation of p53 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). RESULTS: High nuclear p53 expression levels were associated with better outcome for overall survival (OS) (P = 0.0023) and disease-free survival (P = 0.0338) at 5-years. High cytoplasmic p53 expression levels were associated with better outcome for OS (P = 0.0002). In multivariable analysis, high nuclear and high cytoplasmic p53 level with International Federation of Gynecology and Obstetrics (FIGO) stage were the most significant predictor variables for OS and high nuclear p53 level with FIGO stage were the significant predictor variables for disease-free survival. CONCLUSIONS: Assessment of the prognostic value of p53 protein levels using conventional immunohistochemistry is limited by the nonquantitative nature of the method. AQUA provides precise estimation of p53 protein levels and was able to elucidate the association of p53 protein levels and ovarian cancer prognosis.