RESUMO
BACKGROUND : Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2). METHODS: We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria. RESULTS: The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%). CONCLUSIONS: With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.
Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Biópsia por Agulha Fina/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/epidemiologiaRESUMO
Chronic lymphocytic leukaemia (CLL) is a chronic B-cell lympho-proliferative disorder in which lymphomatous transformations occur in 5%-15% of patients. Histologically these cases resemble diffuse large B-cell lymphoma, or Richter's transformation, in over 80% of cases. Rare cases of transformation to Hodgkin lymphoma (HL) have been reported in the literature with an estimated prevalence of 0.4%. We report a case of a 67-year-old female with CLL treated with the novel Bruton's tyrosine kinase (Btk) inhibitor, ibrutinib, who subsequently presented with intractable fevers. Bone marrow trephine, and lymph node biopsy revealed classical HL with negative immuno-histochemistry for Btk in HL cells, on a backdrop of CLL. The patient commenced treatment with Adriamycin, Vinblastine and Dacarbazine (AVD), which resulted in an excellent response. Hodgkin transformation of CLL is rare with a single retrospective study of 4121 CLL patients reporting only 18 cases. Btk expression in HL cells is recently recognised in classical HL; however, the majority of HLs are Btk negative. Given that Btk inhibitors have recently been shown to induce genomic instability in B cells, in the context of their widespread use, such emerging cases are increasingly relevant.
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Doença de Hodgkin/diagnóstico , Doença de Hodgkin/etiologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/etiologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenina/análogos & derivados , Tirosina Quinase da Agamaglobulinemia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Medula Óssea/patologia , Evolução Fatal , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Piperidinas , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversosRESUMO
This study aims to determine the survival impact of patient characteristics and treatment options associated with the early stage oral cavity squamous cell carcinoma, OCSCC. The methods are analysis of Irish cancer database examining T1/2, N0, and M0 cases of OCSCC from 1997 to 2007 inclusive. In total, 397 cases were identified. Anterolateral tongue accounted for 52.9 % of cases. Increased age at diagnosis and smoking are independent prognostic survival indicators associated with poorer outcomes. Surgery as the initial intervention was associated with significantly better survival outcomes, while surgery and adjuvant radiotherapy significantly worse outcomes. Surgical intervention is recommended as the first-line treatment in the early stage OCSCC in combination with elective neck dissection.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Bucais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Bases de Dados Factuais , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Esvaziamento Cervical , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fumar , Resultado do TratamentoRESUMO
Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal tumor of the gastrointestinal tract. The paucity of intracranial metastasis makes treatment strategies difficult. This manuscript presents the first documented case report of a GIST that presented clinically with pituitary symptoms due to a pituitary metastasis.
Assuntos
Tumores do Estroma Gastrointestinal/patologia , Neoplasias Hipofisárias/secundário , Blefaroptose/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças do Nervo Oculomotor/etiologia , Hormônios Hipofisários/sangue , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Campos VisuaisRESUMO
BACKGROUND: Fine needle aspiration biopsy (FNAB) is the tool of choice for evaluating thyroid nodules with the majority classified as benign following initial assessment. However, concern remains about false negative results and some guidelines have recommended routine repeat aspirates. We aimed to assess the utility of routine repeat FNAB for nodules classified as benign on initial biopsy and to examine the impact of establishing a multidisciplinary team for the care of these patients. METHODS: We performed a retrospective review of 400 consecutive patients (413 nodules) who underwent FNAB of a thyroid nodule at our hospital between July 2008 and July 2011. Data recorded included demographic, clinical, histological and radiological variables. RESULTS: Three hundred and fifty seven patients (89 %) were female. Median follow-up was 5.5 years. Two hundred and fifty eight (63 %) nodules were diagnosed as benign. The rate of routine repeat biopsy increased significantly over the time course of the study (p for trend = 0.012). Nine Thy 2 nodules were classified differently on the basis of routine repeat biopsy; one patient was classified as malignant on repeat biopsy and was diagnosed with papillary thyroid carcinoma. Eight were classified as a follicular lesions on repeat biopsy-six diagnosed as benign following lobectomy; two declined lobectomy and were followed radiologically with no nodule size increase. CONCLUSIONS: The false negative rate of an initial benign cytology result, from a thyroid nodule aspirate, is low. In the setting of an experienced multidisciplinary thyroid team, routine repeat aspiration is not justified.
Assuntos
Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Biópsia por Agulha Fina , Reações Falso-Negativas , Humanos , Irlanda , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Susceptibility to environmental carcinogenesis is the consequence of a complex interplay between intrinsic hereditary factors and actual exposure to potential carcinogenic agents. Exposure to sunlight is the primary etiological agent for basal cell carcinoma (BCC). AIM: The aim of this study was to determine the effects of different ultraviolet (UV) doses on DNA damage in epidermal keratinocytes in vivo and to elucidate if patients with BCC are more susceptible to UV-induced DNA damage in comparison with normal healthy volunteers in response to solar simulator radiation (SSR). MATERIALS AND METHODS: Skin biopsies obtained post-UV irradiation from both normal healthy volunteers and BCC patients were analyzed for DNA damage, using immunohistochemical approach with TDM-2 antibody, which binds specifically to cyclobutane pyrimidine dimmers (CPDs). RESULTS: In both normal volunteers and BCC patients, the peak of CPD-positive cells occurred at 4.5 h post-SSR. There was a statistically significant difference in CPD positivity between BCC patients and normal volunteers, at time points (from 4.5 h to 48 h post-SSR). For a given dose of SSR based on each individual minimal erythema dose (MED), a greater number of CPD-positive cells could be shown. CONCLUSIONS: This study has shown for the first time and in vivo in human volunteers that BCC patients are more susceptible to UV-induced DNA damage in comparison with normal healthy volunteers.
Assuntos
Carcinoma Basocelular/metabolismo , Dano ao DNA/efeitos da radiação , Dímeros de Pirimidina/metabolismo , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta/efeitos adversos , Adulto , Idoso , Carcinoma Basocelular/patologia , Relação Dose-Resposta à Radiação , Eritema/metabolismo , Eritema/patologia , Feminino , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Luz Solar/efeitos adversosAssuntos
DNA Nucleotidilexotransferase/metabolismo , Erros de Diagnóstico/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Núcleo Celular/enzimologia , Núcleo Celular/patologia , Reações Falso-Negativas , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/enzimologia , Adulto JovemRESUMO
BACKGROUND: Germ line mutations of the BRCA2 tumor suppressor gene with subsequent loss of the remaining wild-type BRCA2 allele have been identified in up to 35% of familial breast cancer cases. A high frequency of allelic loss at the BRCA2 gene locus has also been reported in a variety of sporadic epithelial tumors including oesophageal squamous cell carcinomas (SCC), and sporadic head and neck SCC. AIM: The present study aimed to examine the integrity of the BRCA2 gene in cutaneous SCC. MATERIALS AND METHODS: Allelic imbalance/loss of heterozygosity (AI/LOH) was examined in 22 histologically confirmed cutaneous SCC at two microsatellite markers, D13S260 (centromeric to the BRCA2 gene) and D13S267 (telomeric to the BRCA2 gene). Immunohistochemical analysis of BRCA2 protein expression was also examined in the cutaneous SCC. RESULTS: AI/LOH at the D13S260 locus was found in eight of the 19 informative SCC, and AI/LOH at the D13S267 locus was found in 12 of the 18 informative SCC. Seven SCC showed allelic loss at both markers, and six SCC showed retention of heterozygosity at both markers. Expression of BRCA2 protein was only detected in six of the normal epidermises and three of the 21 SCC examined. CONCLUSION: AI/LOH of the BRCA2 gene region was found to be common in the cutaneous SCC.
Assuntos
Proteína BRCA2/genética , Carcinoma de Células Escamosas/genética , Genes BRCA2 , Biologia Molecular , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Proteína BRCA2/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/análise , Epiderme/metabolismo , Epiderme/patologia , Feminino , Humanos , Perda de Heterozigosidade , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Aberrations of the tumor suppressor gene, the fragile histidine triad gene (FHIT), have been reported in a wide variety of human cancers including cervical carcinoma, oral squamous cell carcinoma (SCC) and oesophageal SCC. This study aimed to examine the integrity of the FHIT gene in cutaneous SCC. Allelic imbalance/loss of heterozygosity (AI/LOH) was examined in 21 histologically confirmed cutaneous SCC at two microsatellite markers, D3S1300 and D3S4103, both of which are located within intron 5 of the FHIT gene. Immunohistochemical analysis of FHIT protein expression was also examined in the cutaneous SCC. Ten of the 16 informative cutaneous SCC samples (63%) displayed AI/LOH at the D3S1300 locus, and 13 of the 17 informative cutaneous SCC samples (76%) displayed AI/LOH at the D3S4103 locus. Nine of the 21 SCC samples were found to be positive for FHIT protein expression, however, a further nine SCC samples showed reduced FHIT expression, and three SCC samples did not express the FHIT protein. No correlation between AI/LOH of the FHIT gene and reduced/absent FHIT expression was detected in the cutaneous SCC samples. Further investigation into the role of the FHIT protein in the epidermis is warranted to determine if the reduced/lost expression of FHIT observed in a subset of the cutaneous SCC is contributing to tumorigenesis.
Assuntos
Hidrolases Anidrido Ácido/genética , Carcinoma de Células Escamosas/genética , Genes Supressores de Tumor , Perda de Heterozigosidade/genética , Proteínas de Neoplasias/genética , Neoplasias Cutâneas/genética , Hidrolases Anidrido Ácido/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/análise , Humanos , Imuno-Histoquímica , Microdissecção , Repetições de Microssatélites , Proteínas de Neoplasias/metabolismo , Reação em Cadeia da Polimerase , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Objectives Evaluation of the changing trends in esthesioneuroblastoma in an Irish context and review of management options nationally to clarify the best current therapeutic approach by comparing with international research on this uncommon malignancy. Design Retrospective review. Setting Tertiary referral center. Participants All patients presenting with esthesioneuroblastoma in Beaumont hospital or on the National Cancer Registry of Ireland between 1994 and 2013. Main Outcome Measures Recurrence-free and overall survival. Results During the study period, 32 cases of esthesioneuroblastoma were diagnosed (0.4 per million per year). Average age at diagnosis was 57 years; however, two cases were under 20. The majority (62.5%) were male. Patients predominantly presented with epistaxis or nasal congestion (73%), while two cases were identified incidentally on radiological investigations. Twenty-seven cases underwent primary surgical management (two post neo-adjuvant treatment) with seventeen requiring bifrontal craniotomy. Twenty-four of these received postoperative radiation therapy. Overall, 5-year survival was 65%. Kadish A/B patients exhibited 100% 5-year disease-specific survival versus 54% in Kadish C/D ( p = 0.011). Hyams grade I/II patients exhibited 75% 5-year disease-specific survival versus 63% in Hyams grade III/IV ( p = 0.005). Patients treated endoscopically exhibited 100% 5-year disease-specific survival versus 51% in those treated via an open approach ( p = 0.102). Conclusions Many controversies exist in the diagnosis and management of this condition. Despite this, results from Irish data are mostly concordant with the international literature. The rising incidence of this disease may represent improved pathological recognition. An increasing number of esthesioneuroblastoma cases are being successfully treated via endoscopic surgery.
RESUMO
We describe a novel gene fusion, EWSR1-CREM, identified in 3 cases of clear cell carcinoma (CCC) using anchored multiplex polymerase chain reaction, a next-generation sequencing-based technique. CCC is a low-grade salivary tumor recently characterized to have EWSR1-ATF1 fusions in the majority of cases. Three cases of malignant tumor presenting in the base of tongue, lung, and nasopharynx were studied. All cases shared a clear cell morphology with hyalinized stroma, presence of mucin and p63 positivity and were initially diagnosed as mucoepidermoid carcinoma but were negative for evidence of any of the expected gene fusions. Anchored multiplex polymerase chain reaction demonstrated a EWSR1-CREM fusion in all 3 cases to confirm a diagnosis of CCC. This finding is biologically justified as CREM and ATF1 both belong to the CREB family of transcription factors. EWSR1-CREM fusions have not been previously reported in CCC and have only rarely been reported in other tumors. We show that the ability to discover novel gene variants with next-generation sequencing-based assays has clinical utility in the pathologic classification of fusion gene-associated tumors.
Assuntos
Adenocarcinoma de Células Claras/genética , Modulador de Elemento de Resposta do AMP Cíclico/genética , Neoplasias Pulmonares/genética , Neoplasias Nasofaríngeas/genética , Proteína EWS de Ligação a RNA/genética , Neoplasias da Língua/genética , Adenocarcinoma de Células Claras/patologia , Idoso , Feminino , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fusão Oncogênica , Neoplasias da Língua/patologia , TranscriptomaRESUMO
The incidence and aggressiveness of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma (SCC), in immunocompromised renal transplant recipients (RTRs) is dramatically higher (up to 100-fold) compared with the normal population. SCC lesions are also predominant in RTRs, in contrast to the normal population where basal cell carcinoma is more common. The mechanisms underlying this phenomenon are unknown, but effective treatments for these skin tumors would have a significant impact upon morbidity in this group of patients. The fundamental role of telomeres and telomerase in the development of most human cancers, including melanoma, is well established, but very few reports have assessed their function during the onset of nonmelanoma skin cancer. To assess whether telomere maintenance plays any role in the increased incidence of SCC in renal transplant patients, we analyzed both the telomere lengths and telomerase expression levels in 44 SCCs and 22 Bowen's disease (BD) samples (carcinoma in situ) from RTRs and nontransplant patients. Our findings provide statistically significant evidence that the telomeres are consistently longer in both BD RTR and SCC RTR lesions compared with their nontransplant counterparts. We also show by immunohistochemistry that there is a trend toward higher telomerase levels in both the BD RTR and SCC RTR lesions, although this was not statistically significant. Our data thus suggest that telomere lengthening may possibly be an early event in the development of SCC in renal transplant patients and demonstrate that telomere maintenance mechanisms should be further evaluated with respect to developing a future therapeutic strategy for these cancers.
Assuntos
Doença de Bowen/etiologia , Carcinoma de Células Escamosas/etiologia , Transplante de Rim/efeitos adversos , Neoplasias Cutâneas/etiologia , Telômero/genética , Sequência de Bases , Doença de Bowen/enzimologia , Doença de Bowen/genética , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/genética , Linhagem Celular , Células HeLa , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Hibridização in Situ Fluorescente/métodos , Transplante de Rim/estatística & dados numéricos , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/genética , Telomerase/biossínteseRESUMO
Tumor growth depends on 2 distinctive pathways: cell proliferation and apoptosis. The p53 pathway is an important regulator of the cell cycle as it triggers growth arrest or leads to apoptosis in response to cellular stress and therefore is commonly targeted during tumorigenesis. Apoptosis is also controlled by the Bcl-2 family, which includes proapoptotic and antiapoptotic proteins. The aim of this study was to investigate the expression of proteins that are involved in the p53 pathway and apoptosis in different types of soft tissue sarcomas and to correlate the expression of these proteins with the histologic grade of sarcoma cases. One hundred fifty-two cases of different types of soft tissue sarcomas were analyzed. The cases consisted of 54 low-grade, 40 intermediate-grade, and 58 high-grade sarcomas. Immunohistochemical stains for p21(WAF1/CIP1), p53, Mdm2, Bcl-2, and Bax proteins were carried out on tissue microarrays. Nuclear reactivity for p53 was detected in 49 cases (32.2%). Overexpression of Mdm2 was found in 18 cases (11.8%) and p21(WAF1/CIP1) immunostaining was seen in 28 tumors (18.4%). p53 and p21(WAF1/CIP1) expression correlated with the tumor grade (low grade, 5.6% and 3.7%; intermediate grade, 22.5% and 20%; high grade, 63.8% and 31%, respectively). Expression of Bax protein was a common finding in soft tissue sarcoma cases. It was detected in 141 cases (92.8%). Bcl-2 was identified in 59 tumors (38.8%) and was more prevalent in high-grade sarcomas (low grade, 25.9%; intermediate grade, 32.5%; high grade, 55.2%). It was concluded that alterations in the p53 pathway and genes that regulate apoptosis are common events in soft tissue sarcomas. The expression of p53, p21(WAF1/CIP1), and Bcl-2 is closely associated with the histologic grade of the tumor, and therefore these proteins may be used as prognostic markers.
Assuntos
Proteínas de Neoplasias/imunologia , Sarcoma/diagnóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/imunologia , Inibidor de Quinase Dependente de Ciclina p21/análise , Inibidor de Quinase Dependente de Ciclina p21/imunologia , Humanos , Imuno-Histoquímica , Proteínas de Neoplasias/análise , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Proteínas Proto-Oncogênicas c-mdm2/análise , Proteínas Proto-Oncogênicas c-mdm2/imunologia , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/imunologia , Proteína X Associada a bcl-2/análise , Proteína X Associada a bcl-2/imunologiaRESUMO
Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily treated without further complication, some behave more aggressively and carry a poor prognosis. These "high-risk" cutaneous SCCs commonly originate in the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high-risk cutaneous SCC include large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, high-grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high-risk anatomic locations. Both the National Comprehensive Cancer Network® (NCCN® ) and the American Joint Committee on Cancer (AJCC) identify several of these high-risk features of cutaneous SCC. The purpose of this article was to review the high-risk features included in these guidelines, as well as their notable discrepancies and omissions. We also provide a brief overview of current prophylactic measures, surgical options, and adjuvant therapies for high-risk cutaneous SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 578-594, 2017.
Assuntos
Carcinoma de Células Escamosas/patologia , Oncologia/normas , Guias de Prática Clínica como Assunto , Neoplasias Cutâneas/patologia , Biópsia por Agulha , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Medição de Risco , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Sociedades Médicas , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Posttransplant lymphoproliferative disorders (PTLD) are a common malignancy after renal transplantation with a high incidence of PTLD described in the first posttransplant year. We sought to determine incidence and risk determinants of PTLD in Irish kidney transplant recipients. METHODS: Retrospective observational study of 1996 adult first kidney transplant recipients between 1991 and 2010 in the Republic of Ireland. Recipients were cross-referenced with the National Cancer Registry to determine incidence of PTLD. Kaplan-Meier analysis was performed for PTLD-free survival, allograft survival, and patient survival after PTLD. Cox proportional hazards models were used to identify independent risk factors for PTLD in our population. RESULTS: We identified 31 cases of PTLD during the study period. Histological subgroups included: early lesions (n = 1); polymorphic PTLD (n = 1); monomorphic PTLD (n = 27), Hodgkin disease (n = 2). Median time to PTLD diagnosis was 8.3 (range, 1.2-13.9) years. Cumulative incidence (95% CI) of PTLD at 1, 2, 3, 5, 10, and 15 years was 0%, 0.16% (0.05-0.5%), 0.21% (0.08-0.57%), 0.21% (0.08-0.57%), 1.76% (1.15-2.69%), and 3.07% (2.1-4.43%), respectively. Allograft survival after PTLD diagnosis was 94.4% (66.6-99.2%) at 5 years. Patient survival after PTLD diagnosis was 64% at 1 year, 53% at 2 years, 48% at 5 years, and 37% at 10 years. No risk factors for PTLD were identified. CONCLUSIONS: We found a paucity of early onset PTLD in our cohort with no cases in the first posttransplant year. Potential contributing factors included a high prevalence of previous Epstein-Barr virus exposure and a relatively low immunological risk profile in our recipient cohort compared with prior studies. Further studies are required to reevaluate the epidemiology of PTLD in the modern era of transplant immunosuppression.
Assuntos
Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/epidemiologia , Transplantados , Adolescente , Adulto , Aloenxertos , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Incidência , Irlanda/epidemiologia , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. The prediction of the malignant potential of GISTs is still difficult. Altered cell cycle regulation may underlie the tumorigenesis and/or the progression of human malignancies. Although p53 and Bcl-2 have been extensively investigated in GISTs, little is known about the frequency of expression and possible clinical implications of alterations of other cell cycle regulatory proteins in these neoplasms. We have previously investigated the role of loss of p16(INK4A) by loss of heterozygosity and immunohistochemistry in the progression of GISTs and found that loss of heterozygosity of 9p and loss of p16 expression are confined to malignant GISTs. This has led us to investigate the role of other cell cycle regulatory proteins in these tumors. Twenty-three cases of GIST (9 low malignant potential [LMP], 10 primary malignant, and 4 intra-abdominal recurrences) were examined. All cases were strongly positive for KIT (CD117). Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G(1)-S transition and proteins that regulate apoptosis including Rb, E2F1, cyclin D1, CDK4, CDK6, p27(KIP1), p21(WAF1/CIP1), p53, Mdm2, Bcl-2, and Bax. The positive phenotypes identified were as follows: Rb, 39.1%; E2F1, 69.6%; cyclin D1, 30.4%; CDK4, 100%; CDK6, 30.4%; 39.1%; p27(KIP1), 47.8%; p21(WAF1/CIP1), 39.1%; p53, 43.5%; Mdm2, 17.4%; Bcl-2, 91.3%; and Bax, 100%. Malignant GISTs are more likely to be associated with a positive E2F1 and p53 phenotype and a negative p16 and p27(KIP1) phenotype. It was concluded that aberration of the cell cycle regulators is a frequent finding and may be a contributing factor to the pathogenesis of GISTs. While some alterations are seen in LMP and malignant GISTs and therefore may represent an early event in molecular tumorigenesis of GISTs, other alterations are more common in malignant GISTs than LMP and therefore have potential utility as complementary tools for the prognostication of GISTs.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/mortalidade , Regulação Neoplásica da Expressão Gênica/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Ciclo Celular , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Tumores do Estroma Gastrointestinal/classificação , Tumores do Estroma Gastrointestinal/etiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Fatores de TempoRESUMO
The p16 is a tumor suppressor gene on the short arm of chromosome 9p21. The product of the p16 acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein. This study was designed to assess the frequency of genetic loss of 9p21 and to determine the role of p16 the pathogenesis of sporadic and neurofibromatosis 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs). The authors examined 15 cases for p16 protein expression and 10 cases for allelic imbalance (AI)/loss of heterozygosity (LOH) of chromosome 9p. DNA was microdissected from normal and neoplastic tissues. AI/LOH analysis was performed using six microsatellite markers on the 9p region. On immunohistochemical analysis 80% of cases showed abnormal expression of p16. Similarly, 8 of 10 cases revealed genetic loss with at least one microsatellite marker. The most frequent deletion was that within the coding sequence. Of p16 at me D9S974 locus. These findings emphasize the role of loss of p16 in the development of both sporadic and NF1-associated MPNSTs.
Assuntos
Alelos , Cromossomos Humanos Par 9/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Perda de Heterozigosidade , Neoplasias de Bainha Neural/genética , Adolescente , Adulto , Idoso , Células Cultivadas , Cromossomos Humanos Par 9/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias de Bainha Neural/fisiopatologiaRESUMO
Cell cycle regulation depends on a fine balance between cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs) that block the cycle progression. Alterations of the cell cycle regulators are a common feature of many malignant tumors, and some have been shown to have prognostic significance. In this study, 152 cases of different types of soft tissue sarcomas were evaluated for alterations of cell cycle regulator proteins that control the cell cycle progression from G1 to S phase and govern the Rb pathway. Immunohistochemical stains for proteins Rb, E2F1, cyclin D1, CDK4, CDK6, p16, and p27 were carried out on tissue microarrays. The relationship between the expression of these proteins and the histologic grade of the sarcomas was assessed. Altered expression for Rb and p16 proteins was identified in 67.8% and 65.1% of the cases, respectively. Overexpression of E2F1, cyclin D1, CDK4, and CDK6 was detected in 50.7%, 24.3%, 92.1%, and 10.5%, respectively. Overexpression of E2F1 was associated with altered expression of Rb protein. Overexpression of cyclin D1, CDK4, and CDK6 showed an association with normal Rb expression. CDK6 expression revealed a positive correlation with the histologic grade of the sarcoma, and p27 expression was inversely correlated with sarcoma grade. These results suggest that alterations of the Rb pathway proteins are common in soft tissue sarcomas and may participate in their tumorigenesis. CDK6 and p27 showed correlation with the histologic grade of the sarcomas, suggesting that these proteins could be used as prognostic markers.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteína do Retinoblastoma/metabolismo , Sarcoma/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Lipossarcoma/metabolismo , Lipossarcoma/patologia , Prognóstico , Sarcoma/diagnóstico , Sarcoma/patologia , Análise Serial de TecidosRESUMO
Human telomerase reverse transcriptase (hTERT) is a telomerase catalytic subunit that regulates telomerase activity. Telomerase is expressed in many human cancers and cell lines and is thought to contribute to their immortality. Little is known about the expression of telomerase in non-epithelial tumors. The objective of this study was to evaluate hTERT expression in a wide range of soft tissue sarcomas. A total of 154 cases of different types of soft tissue sarcoma (54 low-grade, 40 intermediate-grade, and 60 high-grade cases) were evaluated for hTERT expression using immunohistochemistry on tissue microarrays. hTERT immunoexpression was detected in 59% of cases; it was observed in 46%, 58%, and 72% of low-grade, intermediate-grade, and high-grade sarcoma cases, respectively. The intensity of staining positively correlated with the grade of the sarcomas: diffuse strong positive nuclear staining was identified in 6, 8, and 30 cases of low-grade, intermediate-grade, and high-grade sarcomas, respectively. These results suggest that telomerase expression is more often detected in highly malignant tumors than in low-grade sarcomas and thus may be a critical mechanism in tumor progression.
Assuntos
Imuno-Histoquímica/métodos , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Telomerase/análise , Humanos , Valor Preditivo dos Testes , Sarcoma/classificação , Sarcoma/metabolismo , Neoplasias de Tecidos Moles/classificação , Neoplasias de Tecidos Moles/metabolismo , Telomerase/biossínteseRESUMO
Deletions of the short arm of chromosome 9 have been observed in many tumours and cell lines. This chromosomal region is frequently targeted during malignant transformation because it contains at least two known tumour suppressor genes: p16(INK4) and p15(INK4B). p16(INK4A) acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein and therefore block the progression of the cell cycle from G1 to S phase. The role of p16(INK4A) in the development of synovial sarcoma has not been comprehensively investigated. Ten samples of synovial sarcomas were examined for allelic imbalance/loss of heterozygosity (AI/LOH) of the 9p region and p16 protein expression. DNA was isolated from microdissected sections of normal and tumour cells, amplified by polymerase chain reaction and analysed for AI/LOH by using six microsatellite markers that map to the 9p region. Immunohistochemistry for p16 expression was done. AI/LOH with at least one microsatellite marker on 9p21 was detected in six of ten samples. The most frequent allelic deletions were observed within the coding sequence of p16(INK4A). Loss of p16 immunoreactivity was detected in eight samples, six of which showed evidence of alterations at 9p21 region. These findings suggest a possible role of loss of p16(INK4A) in the development of synovial sarcoma.