RESUMO
Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory dermatosis of unknown etiology involving the genital and/or extragenital area, showing histopathologically a characteristic homogeneization and sclerosis of the superficial collagen with variably dense lymphoid infiltrates. Intraepidermal lymphocytes may be observed, and in some cases may pose differential diagnostic problems with mycosis fungoides (MF). We studied the histopathologic features of 121 cases of LSA with dense lymphoid infiltrates (genital: 94; male:female: 93:1; age range: 2 to 87 y; median age: 11 y; extragenital: 27; male:female: 0.1:1; age range: 11 to 79 y; median age: 59 y), to better characterize the intraepidermal lymphoid infiltrate and to compare genital with extragenital cases. Epidermotropic lymphocytes mimicking the histopathologic features of MF were present in 93.6% of the genital specimens but none of the extragenital cases. Interestingly, typical features of LSA were mssing in 39.4% of genital LSA, and in a further 25.5% were present only focally. Immunohistochemical analyses showed a predominance of CD8+ T-lymphocytes within the epidermis. Molecular studies of the T-cell receptor genes revealed a monoclonal population of T-lymphocytes in nearly half of the cases. Our study shows that MF-like histopathologic features are extremely common in genital LSA but are never encountered in extragenital cases. A diagnosis of MF in the genital area should be made only upon compelling features, keeping in mind the frequent pseudolymphomatous aspects of LSA.
Assuntos
Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Masculinos/patologia , Líquen Escleroso e Atrófico/patologia , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Diagnóstico Diferencial , Europa (Continente) , Feminino , Genes Codificadores dos Receptores de Linfócitos T , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Masculinos/genética , Neoplasias dos Genitais Masculinos/imunologia , Humanos , Líquen Escleroso e Atrófico/genética , Líquen Escleroso e Atrófico/imunologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Micose Fungoide/imunologia , Valor Preditivo dos Testes , Pele/imunologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Linfócitos T/imunologia , Adulto JovemRESUMO
Extracellular vesicles (EVs) are small lipid bound structures released from cells containing bioactive cargoes. Both the type of cargo and amount loaded varies compared to that of the parent cell. The characterisation of EVs in cancers of the male urogenital tract has identified several cargoes with promising diagnostic and disease monitoring potential. EVs released by cancers of the male urogenital tract promote cell-to-cell communication, migration, cancer progression and manipulate the immune system promoting metastasis by evading the immune response. Their use as diagnostic biomarkers represents a new area of screening and disease detection, potentially reducing the need for invasive biopsies. Many validated EV cargoes have been found to have superior sensitivity and specificity than current diagnostic tools currently in use. The use of EVs to improve disease monitoring and develop novel therapeutics will enable clinicians to individualise patient management in the exciting era of personalised medicine.
Assuntos
Biomarcadores Tumorais/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias dos Genitais Masculinos/metabolismo , Transdução de Sinais , Neoplasias Urológicas/metabolismo , Animais , Biomarcadores Tumorais/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias dos Genitais Masculinos/genética , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias dos Genitais Masculinos/patologia , Humanos , Masculino , Prognóstico , Neoplasias Urológicas/genética , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/patologiaRESUMO
Up to 15% of male infertility has an immunological origin, either due to repetitive infections or to autoimmune responses mainly affecting the epididymis, prostate, and testis. Clinical observations and epidemiological data clearly contradict the idea that the testis confers immune protection to the whole male genital tract. As a consequence, the epididymis, in which posttesticular spermatozoa mature and are stored, has raised some interest in recent years when it comes to its immune mechanisms. Indeed, sperm cells are produced at puberty, long after the establishment of self-tolerance, and they possess unique surface proteins that cannot be recognized as self. These are potential targets of the immune system, with the risk of inducing autoantibodies and consequently male infertility. Epididymal immunity is based on a finely tuned equilibrium between efficient immune responses to pathogens and strong tolerance to sperm cells. These processes rely on incompletely described molecules and cell types. This review compiles recent studies focusing on the immune cell types populating the epididymis, and proposes hypothetical models of the organization of epididymal immunity with a special emphasis on the immune response, while also discussing important aspects of the epididymal immune regulation such as tolerance and tumour control.
Assuntos
Epididimo/imunologia , Fertilidade/imunologia , Imunidade Adaptativa , Animais , Neoplasias dos Genitais Masculinos/etiologia , Neoplasias dos Genitais Masculinos/imunologia , Humanos , Imunidade Inata , Infertilidade Masculina/etiologia , Infertilidade Masculina/imunologia , Masculino , Espermatozoides/imunologiaRESUMO
Recent progress in chimeric antigen receptor-modified T-cell (CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment (scFv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin (IL) 12 (named SM3-CAR). The other CAR-T cell line carried the SM3 scFv sequence modified to improve its binding to MUC1 antigen (named pSM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1(+) seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that pSM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.
Assuntos
Neoplasias dos Genitais Masculinos/terapia , Imunoterapia Adotiva/métodos , Proteínas Recombinantes de Fusão/metabolismo , Linfócitos T/transplante , Linhagem Celular Tumoral , Sobrevivência Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Neoplasias dos Genitais Masculinos/genética , Neoplasias dos Genitais Masculinos/imunologia , Células HEK293 , Humanos , Células MCF-7 , Masculino , Mucina-1/genética , Mucina-1/imunologia , Mucina-1/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Glândulas Seminais/patologia , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do TratamentoAssuntos
Neoplasias do Ânus/imunologia , Condiloma Acuminado/imunologia , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Masculinos/imunologia , Infecções por HIV/imunologia , Hospedeiro Imunocomprometido/imunologia , Papillomaviridae/patogenicidade , Feminino , Humanos , MasculinoRESUMO
α-Mucosal human papillomavirus (HPV) types are implicated in a range of clinical conditions and categorized as "low-risk" (LR) and "high-risk" (HR) types according to their degree of association with cervical cancers. The causative role of LR HPV infection in the development of anogenital warts and in low-grade squamous intraepithelial lesions is well established. In addition, there is a growing body of evidence that infection with LR HPV types may be associated with an elevated risk of cancers and potentiation of coinfections. Prospective and case-control studies consistently report a higher risk of anogenital cancers in men and women with a history of anogenital warts. Based on currently available evidence, this higher risk may be due to shared exposure to HR HPV types or an underlying immune impairment, rather than a direct role of LR HPV types in subsequent cancer risk. Data also suggest that infection with LR HPV, HR HPV, or both may increase the risk of HIV acquisition, although the relative contribution of different HPV types is not yet known. There is also evidence implicating HPV clearance, rather than HPV infection, in increased risk of HIV acquisition.
Assuntos
Neoplasias do Ânus/imunologia , Condiloma Acuminado/imunologia , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Masculinos/imunologia , Infecções por HIV/imunologia , Hospedeiro Imunocomprometido/imunologia , Papillomaviridae/patogenicidade , Neoplasias do Ânus/patologia , Neoplasias do Ânus/virologia , Coinfecção , Condiloma Acuminado/complicações , Condiloma Acuminado/patologia , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/virologia , Infecções por HIV/etiologia , Infecções por HIV/patologia , Humanos , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
PURPOSE: Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. METHODS: Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. RESULTS: HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. CONCLUSION: HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers.
Assuntos
Anticorpos Antivirais/sangue , Neoplasias do Ânus/imunologia , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Masculinos/imunologia , Infecções por Papillomavirus/imunologia , Adulto , Idoso , Neoplasias do Ânus/virologia , Biomarcadores Tumorais , Estudos de Casos e Controles , Europa (Continente) , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/virologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Ciências da Nutrição , Proteínas Oncogênicas Virais/imunologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Proteínas Repressoras/imunologia , Resultado do TratamentoRESUMO
Extranodal natural killer (NK)/T-cell lymphoma is a very aggressive malignant neoplasia with a poor prognosis. Herein we reported a case of NK/T cell lymphoma involving mediastinum. It was a 28-year-old Chinese male patient. The tumor cells were medium-sized, had irregularly folded nuclei, and inconspicuous or small nucleoli with coagulative necrosis. The tumor cells were positive for CD3ε, TIA-1, but negative for CD56. In situ hybridization revealed that tumor cells also expressed Epstein-Barr virus encoded RNA. To our knowledge, this is the first case of NK/T cell lymphoma involving mediastinum.
Assuntos
Epididimo/patologia , Neoplasias dos Genitais Masculinos/patologia , Linfoma Extranodal de Células T-NK/patologia , Neoplasias do Mediastino/patologia , Adulto , Biomarcadores Tumorais/análise , Biópsia , Epididimo/imunologia , Epididimo/virologia , Evolução Fatal , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias dos Genitais Masculinos/virologia , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Linfoma Extranodal de Células T-NK/imunologia , Linfoma Extranodal de Células T-NK/virologia , Masculino , Neoplasias do Mediastino/imunologia , Neoplasias do Mediastino/virologia , RNA Viral/genética , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Human papillomavirus (HPV) is the etiological agent for cervical cancer and a large majority of anal cancers worldwide. In 2006 two preventive vaccines against the HPV were approved by the US Food and Drug Administration and have since been approved in over 100 countries. HIV-infected populations are at an increased risk for HPV-related cancers. None of the efficacy trials for these vaccines included HIV-infected populations. However, studies in HIV-infected children and adult men show that the vaccine is safe and highly immunogenic. Studies evaluating the vaccine in HIV-infected women are in progress. Based on these studies, the American Council on Immunization Practices recommends HPV vaccination for all HIV-infected children and young adults up to age 26 years. HPV vaccine policies in resource-limited countries, many of which have a high prevalence of HIV infection, are still being developed. Future studies should examine the role of HPV vaccination for older HIV-infected adults who likely have ongoing HPV infection.
Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Neoplasias do Ânus/prevenção & controle , Neoplasias dos Genitais Femininos/prevenção & controle , Neoplasias dos Genitais Masculinos/prevenção & controle , Neoplasias Orofaríngeas/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Neoplasias do Ânus/imunologia , Neoplasias do Ânus/virologia , Criança , Países em Desenvolvimento , Feminino , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias dos Genitais Masculinos/virologia , Humanos , Masculino , Neoplasias Orofaríngeas/imunologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/economia , Prevalência , Estados Unidos/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro. METHODS: Fifteen patients developed the following malignancies at a mean of 90.3 months (range = 10-252) after kidney transplantation: metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 2), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD; n = 4), renal cell carcinoma T1 (n = 1), MALT lymphoma (n = 1), intramucous colon carcinoma (n = 1), liposarcoma of the spermatic cord (n = 1). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 3), or associated with steroids (n = 6) or with mycophenolate mofetil (n = 6). RESULTS: Both patients with metastatic cancer underwent chemotherapy but succumbed after 6 and 13 months. Two patients with PTLD who underwent chemotherapy died after 12 and 36 months. At a mean follow-up of 32.7 months (range = 7-56), the remaining 11 patients are cancer-free. Two patients lost their grafts after 24 and 36 months after the switch due to chronic rejection. Renal graft function remained stable in all other patients from diagnosis throughout follow-up. CONCLUSION: Our observations suggested that rapamycin-based immunosuppression offers the possibility for regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was due to rapamycin treatment or to the reduced immunosuppression.
Assuntos
Transplante de Rim/imunologia , Neoplasias/imunologia , Sirolimo/uso terapêutico , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias dos Genitais Masculinos/patologia , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Lipossarcoma/imunologia , Lipossarcoma/patologia , Masculino , Metástase Neoplásica , Neoplasias/epidemiologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologiaRESUMO
OBJECTIVES: To study paratesticular malignant fibrous histiocytomas (FHM) from the clinical, histological, immunohistochemical and histogenetic, point of view. METHODS: Through Medline and not index-linked search of international scientific literature we have found a total of 77 cases of paratesticular FHM that globally create diagnostic, terminological and therapeutic problems. RESULTS: We include the case number 78 of FHM of spermatic cord, that presents a few special characteristics (not described before) of cutaneous fistula and infiltration of an inguinal leiomyoma, with histological and immunohistochemical confirmation. We performed a conceptual review of this type of tumours, including the evaluation of contradictions and reclassifications that has undergone from its first description, which causes that they are underestimated and their real prevalence in international series is very variable: from 7 to 37% of paratesticular sarcomas. Also, the fact of their low incidence has determined the lack of protocols for diagnosis and treatment. CONCLUSIONS: Paratesticular tumours, although infrequent, have a high rate of malignancy. The FHM concept has varied throughout the last 15 years. Today, this term is synonymous of pleomorphic undifferentiated sarcoma and has been an exclusion diagnosis (Vimentin [+]/ CD 68 [+]--occasionally--without ultrastructural differences), reserving the inflammatory subtype for which they have an inflammatory and histiocytic component. The accomplishment of an intraoperatory biopsy is essential in this location, since it is even difficult to know preoperatively, if a lesion is benign or malignant. The differential diagnosis is only solved after microscopic and inmunohistochemical study. Leiomyoma next to this location (inguinal) could be diagnosed and confused with a nodule of the main FHM. Their immunophenotype allowed us to diagnose it not only as leiomyoma (myogenic markers were positive -non skeletal muscle-), but also to observe the infiltration by the FHM.
Assuntos
Neoplasias dos Genitais Masculinos/patologia , Histiocitoma/patologia , Canal Inguinal , Leiomioma/patologia , Neoplasias Primárias Múltiplas/patologia , Cordão Espermático , Idoso de 80 Anos ou mais , Neoplasias dos Genitais Masculinos/imunologia , Histiocitoma/imunologia , Humanos , Imunofenotipagem , Inflamação/patologia , Masculino , Invasividade Neoplásica , Neoplasias Primárias Múltiplas/imunologiaRESUMO
Human papillomaviruses (HPV) induce benign and malignant tumors of skin and mucosa. Non-melanoma skin cancer (NMSC) is the most frequent malignancy in fair-skinned populations, particularly frequent in countries with high sun exposure and in immunosuppressed patients. The high prevalence of Beta-HPV in skin tumors renewed interest in a possible etiologic role of HPV. In contrast to cervical cancer, the presence of HPV is probably not mandatory for maintenance of the malignant phenotype of skin cancer cells, since only low copy numbers of HPV DNA persist in skin cancers. Higher viral loads in actinic keratoses are compatible with a carcinogenic role of cutaneous HPV in early phases of NMSC development. There is some evidence from case-control studies for an increased risk of cutaneous squamous cell carcinoma related to beta-HPV infection. HPV8 is clearly carcinogenic in transgenic mice. At the molecular level, oncogenic activities of beta-HPV have been attributed to effective inhibition of apoptosis and interference with DNA repair pathways by viral E6 proteins. In addition E7 proteins deregulate the cell cycle and enhance invasive growth.
Assuntos
Neoplasias dos Genitais Femininos/virologia , Modelos Biológicos , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/virologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/virologia , Feminino , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias dos Genitais Masculinos/virologia , Humanos , Masculino , Infecções por Papillomavirus/imunologiaRESUMO
A 51-year-old man without human immunodeficiency virus, hepatitis B virus or hepatitis C virus was admitted with left scrotum swelling and hydrocele. The cytological finding of fluid in the left scrotum revealed malignant lymphoma, and the immunophenotypic analysis and monoclonal rearrangement of immunoglobulin heavy chain demonstrated B-cell lymphoma. However, no solid tumor of lymphoma was identified in the specimen following a left orchiectomy, or in any other body site and genomic human herpes virus-8 and Epstein-Barr virus were not detected in the lymphoma cells. So we interpreted this as a primary effusion lymphoma without any ethological viral infection. Subsequently, he underwent chemo-radiation therapy and has remained in remission.
Assuntos
Neoplasias dos Genitais Masculinos/diagnóstico , Linfoma de Células B/diagnóstico , Escroto , Citodiagnóstico , Neoplasias dos Genitais Masculinos/imunologia , Humanos , Imunofenotipagem , Linfoma de Células B/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
A 66-year-old male, whose primary skin lesion in extramammary Paget's disease had been surgically resected 4 years previously, was hospitalized with liver metastases. Hepatic arterial infusion chemotherapy was carried out and the tumours clearly reduced in size. Serum levels of some common tumour markers were not elevated, even prior to therapy. We measured serum levels of a novel tumour-associated antigen, RCAS1, because its expression was detected in the tumour cells. The patient's serum RCAS1 level was elevated (22.0 U/mL) before therapy and fell during (10.5 U/mL) and after (5.0 U/mL) therapy. Therefore, serum RCAS1 levels may be valuable as a potential biomarker for monitoring therapeutic efficacy against Paget's disease.
Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias Hepáticas/imunologia , Doença de Paget Extramamária/imunologia , Escroto , Neoplasias Cutâneas/imunologia , Idoso , Neoplasias dos Genitais Masculinos/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Doença de Paget Extramamária/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Previous studies using primary monolayer cultures of epithelial cells from the involved epidermis of patients with mammary and extramamary Paget's disease investigated whether Paget cells proliferate as other malignant cells do. Although epithelial monolayers from the involved skin were maintained for approximately 45 days, no permanent cell lines were established. The proportion of carcinoembryonic antigen (CEA)-positive cells did not increase in the long-term cultures. Herein, we report studies of whether there is a real reduction of Paget cell numbers or if this is merely a decrease in the expression of CEA by the cells. Furthermore, we investigated whether Paget cells survive longer when cultured free from any potential inhibitory keratinocytes or other epidermal cells. Skin samples were obtained from one patient with mammary Paget's disease and three with extramammary Paget's disease; epidermal cells were cultured in vitro. An enrichment of Paget cells was carried out from the cultured epidermal cells by combining an antiepithelial membrane antigen monoclonal antibody, binding to immunobeads, and density gradient centrifugation in Nycodenz. The separated cells were re-cultured in Keratinocyte-SFM serum-free media. The proportion of CEA-positive cells did not increase in the culture, and the purified cells did not show any increase in survival times compared to the non-purified cultured cells. These results suggest that the decrease of CEA-positive cells noted during culture results from a decline in expression of CEA in the Paget cells. Paget cells in the involved epidermis do not proliferate significantly and thus differ from many other malignant cells.
Assuntos
Antígeno Carcinoembrionário/metabolismo , Mucina-1/metabolismo , Doença de Paget Extramamária/imunologia , Doença de Paget Mamária/imunologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/imunologia , Contagem de Células , Meios de Contraste , Feminino , Neoplasias dos Genitais Masculinos/imunologia , Humanos , Técnicas In Vitro , Iohexol , Masculino , Microscopia de Fluorescência , Células Tumorais CultivadasRESUMO
Immunophenotypes of mammary (MPD) and extramammary Paget's disease (EPD) are still not well understood. Thirty-four formalin-fixed paraffin-embedded tissue sections from 33 patients with 6 MPD and 28 EPD were studied immunohistochemically with the use of polyclonal c-erbB-2 and pS2 antisera, and monoclonal nm23, B6.2, GCDFP-15, and p53 antibodies. Cases of MPD expressed a high incidence of c-erbB-2 and nm23 compared with those of EPD (100% vs. 29%; p < 0.01, and 83% vs. 29%; p < 0.05, respectively). Although high expression of B6.2 (> 83%) and moderate expression of GCDFP-15 (33-39%), pS2 (33-46%) and p53 (39-50%) were seen, the positivity was not significantly different between MPD and EPD. These findings indicate that MPD and EPD share immunohistochemical features but partially differ in their patterns of antigen expression.
Assuntos
Apolipoproteínas , Neoplasias da Mama/patologia , Neoplasias dos Genitais Masculinos/patologia , Glicoproteínas , Proteínas de Membrana Transportadoras , Proteínas Monoméricas de Ligação ao GTP , Núcleosídeo-Difosfato Quinase , Doença de Paget Extramamária/patologia , Doença de Paget Mamária/patologia , Proteínas , Neoplasias Vulvares/patologia , Antígenos de Neoplasias/análise , Neoplasias do Ânus/química , Neoplasias do Ânus/imunologia , Neoplasias do Ânus/patologia , Apolipoproteínas D , Axila , Neoplasias da Mama/química , Neoplasias da Mama/imunologia , Carcinoma Intraductal não Infiltrante/química , Carcinoma Intraductal não Infiltrante/imunologia , Carcinoma Intraductal não Infiltrante/patologia , Proteínas de Transporte/análise , Feminino , Expressão Gênica , Neoplasias dos Genitais Masculinos/química , Neoplasias dos Genitais Masculinos/imunologia , Humanos , Masculino , Nucleosídeo NM23 Difosfato Quinases , Proteínas de Neoplasias/análise , Doença de Paget Extramamária/química , Doença de Paget Extramamária/imunologia , Doença de Paget Mamária/química , Doença de Paget Mamária/imunologia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Fatores de Transcrição/análise , Fator Trefoil-1 , Proteínas Supressoras de Tumor , Neoplasias Vulvares/química , Neoplasias Vulvares/imunologiaRESUMO
The expression of proliferating cell nuclear antigen (PCNA) was studied in human papillomavirus (HPV)-infected, benign and malignant lesions of the genital tract and larynx using immunocytochemical staining of formalin-fixed clinical specimens. We observed the induction of PCNA in squamous carcinomas and adenocarcinomas, as has been demonstrated with other malignancies. In addition, the differentiated keratinocytes of the upper spinous cells and granulocytes in condylomata acuminata and low-grade intraepithelial neoplasias showed a consistent induction of PCNA compared with the normal squamous epithelium, in which only some of the parabasal and basal cells were positive. This reactivation of PCNA synthesis correlated with the presence of high copy numbers of HPV DNA and was independent of the oncogenic risk potential of the infecting HPV genotype. We postulate that HPV gene products induce the expression of PCNA and other components of the host DNA replication machinery in differentiated cells of squamous lesions to facilitate vegetative viral replication.
Assuntos
Antígenos de Neoplasias/análise , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Queratinócitos/imunologia , Proteínas Nucleares/análise , Papiloma/patologia , Papillomaviridae , Infecções por Papillomavirus/patologia , Infecções Tumorais por Vírus/patologia , Carcinoma in Situ/imunologia , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/virologia , Condiloma Acuminado/imunologia , Condiloma Acuminado/patologia , Feminino , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/virologia , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Queratinócitos/virologia , Neoplasias Laríngeas/imunologia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/virologia , Masculino , Papiloma/imunologia , Papiloma/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/imunologia , Antígeno Nuclear de Célula em Proliferação , Infecções Tumorais por Vírus/imunologiaRESUMO
We studied 69 cases of malignant lymphoma of the testis, epididymis, and spermatic cord, including 64 cases in which the tumor involved these sites at presentation and five cases in which lymphoma relapsed in the testis. The patients without prior lymphoma were 16 to 91 (mean, 56) years old. Fifty-two patients had diffuse large-cell lymphomas [seven large cleaved cell (two with follicular areas), 27 large noncleaved, two multilobated, six not otherwise specified (NOS), 10 immunoblastic]; six, small noncleaved cell; two, diffuse mixed small and large cell; one, diffuse small cleaved; one, follicular mixed small cleaved and large cell; and two, high grade, unclassified in the Working Formulation. Twenty-nine cases (55%) were stage I; five (9%), stage II; one (2%), stage III, and 18 (34%), stage IV. Forty patients (73%) achieved a complete remission; 23 had a relapse of tumor at 4 to 274 months (median, 13) and five were salvaged. At last follow-up, 20 (36%) patients were free of disease, six (11%) were alive with disease, and 29 (53%) had died of lymphoma. Features associated with longer disease-free actuarial survival (DFS) included stage I disease (p = 0.0001) and sclerosis (p = 0.0001). Among patients with stage I lymphoma, those with right-sided tumors (p = 0.005) or tumors with sclerosis (p = 0.0017) had longer DFS. Lymphomas with extensive sclerosis were all stage I (p = 0.0057). Four of five patients with secondary testicular lymphoma had extranodal primary sites. They ranged from 13 to 66 years (median, 35). Testicular relapses occurred 13-37 months after initial diagnosis. Three had diffuse large, noncleaved cell type; one, lymphoblastic and one, diffuse mixed small and large cell. Immunophenotyping showed B lineage in 33 cases and T lineage in one case. Most testicular lymphomas are B-lineage large-cell lymphomas, which frequently involve other extranodal sites at presentation and at relapse, and which often have an aggressive clinical course.
Assuntos
Epididimo , Neoplasias dos Genitais Masculinos/patologia , Linfoma/patologia , Cordão Espermático , Neoplasias Testiculares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias dos Genitais Masculinos/mortalidade , Humanos , Imunofenotipagem , Linfoma/imunologia , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Esclerose , Taxa de Sobrevida , Neoplasias Testiculares/imunologia , Neoplasias Testiculares/mortalidadeRESUMO
The tumor associated antigen CA50 was examined in serum level of 84 patients with genitourinary malignancies, 48 patients with genitourinary benign diseases and 35 normal persons by immunoradiometric assay (IRMA). The mean CA50 value in the patients with genitourinary malignancy was much higher then that in patients with benign genitourinary diseases and that in the normal control group (P < 0.05-0.01). Taking 17 u/ml as the upper limit of normal range, the positive rates were 55% (11/20) of patients with renal cell carcinoma, 78% (7/8) in pyeloureteric carcinoma, 65% (30/46) in bladder cancer and 70% (7/10) in genital malignancies. The sensitivity of CA50 for the patients with genitourinary malignancy was 65.5% (55/84) and the specificity was 87.5% (42/48). The measurement of level of serum CA50 also could be used to monitor the clinical change and responses during the course of treatment. It might be helpful to predict the recurrence of tumor after surgical treatment.
Assuntos
Antígenos Glicosídicos Associados a Tumores/análise , Biomarcadores Tumorais/análise , Neoplasias dos Genitais Masculinos/imunologia , Neoplasias Urológicas/imunologia , Adulto , Idoso , Carcinoma de Células Renais/imunologia , Carcinoma de Células Escamosas/imunologia , Humanos , Neoplasias Renais/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/imunologiaRESUMO
Peripheral blood mononuclear cells (PBMC) from patients with active HPV16-associated pre-malignant and malignant anogenital lesions display a significantly decreased NK-cell activity against HPV16-harboring SKv keratinocytes (NK/SKv) while their cytotoxicity against erythroleukemic K562 cells (NK/K562) remains unaffected. A similar defect can also be seen in some healthy individuals displaying no symptoms of HPV infection (low responders). Analysis with specific Leu IIa monoclonal antibodies (MAbs) has revealed that all patients as well as weakly responding control subjects had normal numbers of circulating CD16+ NK cells. However, PBMC from patients with active disease and weakly responding controls displayed a significantly decreased ability to bind SKv cells. Binding of K562 was in the normal range. In patients in whom the lesions were successfully removed or regressed spontaneously (patients with no lesions), NK/SKv activity did not differ from that of normally responding healthy subjects and the ability of their PBMC to bind SKv cells was unaffected. To determine whether an abrogated NK/SKv cytotoxicity may be corrected by NK-cell stimulatory cytokines. PBMC were pre-incubated overnight with IL-2 and interferon-alpha. Both cytokines stimulated NK/K562 activity in all tested groups. Significant stimulation of NK/SKv activity was observed in PBMC from normal and weakly responding controls as well as patients with no lesions. No increase could be seen in patients with active disease. Evaluations of NK-cell activity before and after surgical removal or spontaneous regression of the lesions showed normalization of primarily depressed NK/SKv activity. Malignant progression was associated with a significant drop in SKv cell killing. Our results suggest that abrogation of NK-cell activity against HPV16-harboring targets in patients with HPV16-associated anogenital neoplasia is associated with restricted inability to recognize the disease-specific target cells, and may depend on persistence of the lesions.