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1.
Medicine (Baltimore) ; 100(12): e24697, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761637

RESUMO

RATIONALE: Carcinosarcoma and sarcomatoid carcinoma of the stomach are rare, malignant, and biphasic tumors with high mortality. The differential diagnosis of these 2 diseases remains challenging. In the present study, we present 2 cases of carcinosarcoma and sarcomatoid carcinoma of the stomach. PATIENT CONCERNS: A 54-year-old woman was admitted with complaints of epigastric pain for 4 months, but she became serious for 10 days accompanied by melena. A 75-year-old man was admitted with complaints of epigastric pain for 1 month. DIAGNOSIS: The female had a Borrmann type III irregular ulcerative lesion (5.0 × 4.0 × 1.0 cm) originating from the gastric antrum. The male had Borrmann type I tumor polypoid exophytic (5.0 × 4.0 × 2.0 cm) in the fundus of stomach near the cardia. Both cases were identified as malignant neoplasms by endoscopic biopsy and further confirmed by performing laparoscopic proximal gastrectomy, esophagogastrostomy, and palliative distal subtotal gastrectomy. The postoperative histopathological morphology and immunohistochemistry studies revealed sarcomatoid carcinoma for the female and gastric carcinosarcoma for the male respectively. INTERVENTIONS: The female patient subsequently underwent laparoscopy-assisted radical distal gastrectomy for gastric cancer followed by systemic chemotherapy with oxaliplatin plus tegafur. The male patient underwent laparoscopic proximal gastrectomy and esophagogastrostomy were performed. OUTCOMES: The female had a mixture of a little poorly-differentiated adenocarcinoma and abundant sarcomatoid spindle cell elements, and is still alive healthy up to date for 2 and a half years after surgery by phone follow-up. The male patient had both adenocarcinoma and fibrosarcoma in a single tumor, and died 1 month after the operation. LESSONS: The present study provides insight into the clinical findings, differential diagnosis, and prognosis of carcinosarcomas and sarcomatoid carcinomas of the stomach. More cases are needed for further studies in the future.


Assuntos
Carcinoma/diagnóstico , Carcinossarcoma/diagnóstico , Neoplasias Gástricas/diagnóstico , Dor Abdominal/etiologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/complicações , Carcinoma/patologia , Carcinoma/terapia , Carcinossarcoma/complicações , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Quimioterapia Adjuvante , Diagnóstico Diferencial , Evolução Fatal , Feminino , Gastrectomia , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastroscopia , Humanos , Biópsia Guiada por Imagem , Laparoscopia , Masculino , Melena/etiologia , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Tegafur/uso terapêutico , Resultado do Tratamento
2.
J Clin Pathol ; 74(4): 264-268, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33597222

RESUMO

DNA mismatch repair (MMR) proteins are essential for the recognition and correction of sporadic genetic mutations that occur during DNA replication. Deficient MMR function (dMMR) leads to an increased risk of development of neoplasia. Identification of dMMR within tumours can suggest a high chance of the inherited cancer condition Lynch syndrome and predicts poor clinical response to certain conventional chemotherapies but an increased likelihood of response to immunotherapy. This review provides an update on the biology of MMR proteins, their encoding genes and mechanisms for the development of dMMR. This is followed by a discussion of the identification and significance of dMMR in routine clinical practice.


Assuntos
Adenoma/genética , Biomarcadores Tumorais/genética , Carcinoma/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/genética , Mutação , Adenoma/enzimologia , Adenoma/patologia , Adenoma/terapia , Biomarcadores Tumorais/metabolismo , Biópsia , Carcinoma/enzimologia , Carcinoma/patologia , Carcinoma/terapia , Neoplasias Colorretais Hereditárias sem Polipose/enzimologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Enzimas Reparadoras do DNA/metabolismo , Predisposição Genética para Doença , Humanos , Fenótipo
3.
Virchows Arch ; 478(2): 153-190, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33604759

RESUMO

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.


Assuntos
Carcinoma/terapia , Neoplasias do Endométrio/terapia , Oncologia/normas , Biomarcadores Tumorais/genética , Biópsia/normas , Carcinoma/genética , Carcinoma/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Medicina Baseada em Evidências/normas , Feminino , Humanos , Técnicas de Diagnóstico Molecular/normas , Estadiamento de Neoplasias/normas , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento
4.
Cancer Invest ; 39(3): 235-239, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33538211

RESUMO

Comprehensive molecular testing of individual tumors has led to the identification of novel molecularly defined cancer therapies and treatment indications. Given low frequencies of many molecular alterations, efficacy of therapies used to target them are often undefined, especially in the context of rare malignancies. Here we describe the first reported case of MET amplification in sinonasal undifferentiated carcinoma (SNUC), a rare cancer with a poor prognosis. The patient was treated with crizotinib, a tyrosine kinase inhibitor that targets c-MET, and experienced a complete response. Our report demonstrates the potential of employing precision oncology approaches in SNUC and other rare cancers.


Assuntos
Carcinoma/terapia , Crizotinibe/farmacologia , Neoplasias do Seio Maxilar/terapia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Carcinoma/diagnóstico por imagem , Carcinoma/genética , Carcinoma/patologia , Feminino , Amplificação de Genes/efeitos dos fármacos , Humanos , Neoplasias do Seio Maxilar/diagnóstico por imagem , Neoplasias do Seio Maxilar/genética , Neoplasias do Seio Maxilar/patologia , Terapia de Alvo Molecular , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas c-met/genética
5.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431443

RESUMO

Pubic osteomyelitis is a rare and often late-onset complication of radiation therapy and surgery for vulvar and vaginal carcinoma. It typically presents with vulvar pain, fever, vaginal discharge and/or gait disorders. Pubic osteomyelitis is often accompanied by fistulas or wound dehiscence in the pelvic area. Its accurate diagnosis and treatment are challenging and require a multidisciplinary team effort. In our patients, multiple combined surgical procedures, long-term antibiotic treatment and days to weeks of hospital admission were necessary to treat pubic osteomyelitis. We emphasise the importance of timely and adequate diagnosis and multidisciplinary approach resulting in a course of treatment that is as effective as possible, limiting the impact on quality of life, which is generally high in this group of patients.


Assuntos
Carcinoma/terapia , Quimiorradioterapia Adjuvante/efeitos adversos , Osteomielite/terapia , Lesões por Radiação/terapia , Ferida Cirúrgica/terapia , Neoplasias Vulvares/terapia , Adulto , Antibacterianos/uso terapêutico , Artrodese , Transplante Ósseo , Carcinoma/patologia , Feminino , Humanos , Aplicação de Sanguessugas , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Osteomielite/diagnóstico , Osteomielite/etiologia , Equipe de Assistência ao Paciente , Osso Púbico/diagnóstico por imagem , Osso Púbico/efeitos da radiação , Osso Púbico/cirurgia , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/efeitos da radiação , Articulação Sacroilíaca/cirurgia , Transplante de Pele , Ferida Cirúrgica/complicações , Resultado do Tratamento , Vulva/patologia , Vulva/cirurgia , Neoplasias Vulvares/patologia
6.
Medicine (Baltimore) ; 99(41): e22671, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031333

RESUMO

Epithelial-myoepithelial carcinoma (EMC) is a rare neoplasm of the salivary glands. The aim of this study is to review and evaluate clinicopathological features and treatment of EMC of salivary gland for better sensitivity and specificity of the diagnosis.The clinical and pathological data of the 10 salivary gland EMC cases from 2008 to 2017 were analyzed.Six cases of EMC were diagnosed to be originated from parotid gland and 4 cases were from the minor salivary gland including palate, tongue, and oropharynx. Seven cases were performed radical surgery and 3 cases had radiotherapy postoperation, 2 cases had a local recurrence. The follow-up period was 4 to 104 months and the survival rate was 100%. Histopathology showed the tumors had a dominant prototypical biphasic tubular structure consisting of inner, cuboidal ductal cells and an outer layer of clear, myoepithelial cells, which grew infiltratively. The immunohistochemistry (IHC) showed the marker proteins CK, S-100, CD117, and Calponin were strongly positive in most EMC.EMC is a rare and low-grade malignant tumor with good overall survival but relatively high tendency for local recurrence. Surgery is the priority choice for EMC therapy. Complete surgical excision and negative margins are necessary for good prognosis. Imaging techniques should be used to assess the neck dissection and it is unclear whether adjuvant radiotherapy is beneficial. To ensure the sensitivity and specificity of the EMC diagnosis, we should perform both pathological and IHC analysis.


Assuntos
Carcinoma/patologia , Mioepitelioma/patologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mioepitelioma/terapia , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/terapia
7.
HNO ; 68(12): 927-934, 2020 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-32929519

RESUMO

INTRODUCTION: Salivary gland carcinomas (SGCs) are rare tumors which represent a challenge for diagnosis and therapy due to their histological diversity and the different disease courses depending on the respective subtype. Little is known about the composition of the tumor microenvironment in SGCs. A more comprehensive understanding of the relevant molecular changes and immunological processes of the tumor and surrounding stroma could help to improve therapeutic efficiency, for example by adjuvant immunomodulation. METHODS: This manuscript highlights recent studies analyzing the composition of the tumor microenvironment in salivary gland carcinomas. RESULTS: The tumor microenvironment displays a significant diversity in the composition of immune cells among different tumor entities. In one third of the SGCs, an expression of cell surface molecule LAG3 on tumor infiltrating lymphocytes could be observed. LAG3-similar to CTLA­4 and PD-1-inhibits cellular proliferation, activation, and homeostasis of antitumor-effective T cells. Especially, prognostically less favorable entities such as salivary duct carcinomas and adenocarcinomas NOS (not otherwise specified) yielded higher expressions. CONCLUSIONS: LAG3 is particularly detectable in aggressive entities and advanced tumors. Hence, LAG3 inhibition poses a potential targeted therapy for advanced and metastatic SGCs.


Assuntos
Carcinoma , Neoplasias das Glândulas Salivares , Biomarcadores Tumorais , Carcinoma/terapia , Humanos , Linfócitos do Interstício Tumoral , Neoplasias das Glândulas Salivares/terapia , Glândulas Salivares , Microambiente Tumoral
8.
Rev. ORL (Salamanca) ; 11(3): 329-339, jul.-sept. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-197901

RESUMO

El cáncer de tiroides es la neoplasia endocrina más frecuente. Su incidencia en los últimos años ha aumentado, requiriendo estrategias de vigilancia que garanticen un manejo individualizado y efectivo de los pacientes. El objetivo principal de la siguiente revisión es brindar pautas de seguimiento a corto y largo plazo, guiándonos por una adecuada estratificación de riesgo de los pacientes y reclasificación de su respuesta al tratamiento


Thyroid cancer is the most common endocrine neoplasia. Its incidence in recent years has increased, requiring surveillance strategies that guarantee individualized and effective patient management. The main objective of the following review is to provide short-term and long-term follow-up guidelines, guiding us through adequate stratification of patient risk and reclassification of their response to treatment


Assuntos
Humanos , Carcinoma/terapia , Carcinoma Anaplásico da Tireoide/terapia , Seguimentos , Neoplasias da Glândula Tireoide/prevenção & controle , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/epidemiologia
9.
Ann Otol Rhinol Laryngol ; 129(12): 1215-1220, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32546006

RESUMO

BACKGROUND: Oral cavity carcinomas individually are the fifth-leading cause of overall cancer mortality in the Northern Mariana Islands, which is likely a representative statistic for many other betel-nut-endemic Pacific islands. Factors associated with survival have been minimally evaluated in this region. The purpose of this study is to further characterize oral cavity carcinoma outcomes and associated prognostic factors in the United States commonwealth of the Northern Mariana Islands (CNMI). METHODS: A single-institution retrospective review was undertaken for 81 patients diagnosed with head and neck cancers at the CNMI's only regional hospital complex from 2005 to 2019. A subset of patients diagnosed with oral cavity carcinoma was further evaluated for survival outcomes. Cox proportional hazard regressions were performed to evaluate for variables associated with survival. RESULTS: A majority of patients had cancer of the oral cavity (64/81, 79%). Fifty-five of these patients had sufficient data for review. The average age at the time of diagnosis was 48 and over half were diagnosed with stage IV disease (29/55, 53%). Five-year overall survival (OS) was 49.5% (95% CI, 33.3-63.7%). Factors associated with worse OS were lymph node metastases at presentation (P = .031), higher overall stage (III or IV vs I or II, P = .016), and higher T-stage (III or IV vs I or II, P = .027). Those who used betel nut were diagnosed at a significantly younger age than those who did not (47.2 vs 55.4, P = .001). CONCLUSIONS: The head and neck cancer burden in the CNMI is dominated by betel nut related oral cavity disease that is characterized by delayed presentations in younger patients and decreased OS. Future studies are indicated to improve health literacy as well as to investigate the potential for screening programs.


Assuntos
Antineoplásicos/uso terapêutico , Areca , Carcinoma/terapia , Neoplasias Bucais/terapia , Procedimentos Cirúrgicos Otorrinolaringológicos , Radioterapia , Adulto , Carcinoma/mortalidade , Carcinoma/patologia , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Micronésia/epidemiologia , Pessoa de Meia-Idade , Mucosa Bucal , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Grupo com Ancestrais Oceânicos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Uso de Tabaco/epidemiologia , Adulto Jovem
10.
In Vivo ; 34(3 Suppl): 1661-1665, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503826

RESUMO

COVID-19 has been officially declared as a pandemic by the WHO. Italy was the first European country to be strongly affected by this outbreak. All elective and health promotion activities were reduced. Accordingly, Italian Breast Units and breast cancer (BC) screening programs scaled down significantly their activities. The aim of this study was to evaluate measures that could potentially reduce the clinical impact of COVID-19 on BC patients. Temporary recommendations are needed that could assist specialists in preventing COVID-19 infection and optimizing resources for diagnosis and treatment of BC patients.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Infecções por Coronavirus , Procedimentos Cirúrgicos Eletivos/psicologia , Hospitais Universitários , Hospitais Urbanos , Mastectomia/psicologia , Pandemias , Pneumonia Viral , Recusa do Paciente ao Tratamento/psicologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/psicologia , Neoplasias da Mama/cirurgia , Carcinoma/diagnóstico por imagem , Carcinoma/psicologia , Carcinoma/cirurgia , Carcinoma/terapia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/psicologia , Carcinoma Intraductal não Infiltrante/cirurgia , Terapia Combinada , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/psicologia , Diagnóstico Tardio , Gerenciamento Clínico , Detecção Precoce de Câncer , Estrogênios , Feminino , Humanos , Mamografia , Programas de Rastreamento , Terapia Neoadjuvante , Neoplasias Hormônio-Dependentes/diagnóstico por imagem , Neoplasias Hormônio-Dependentes/psicologia , Neoplasias Hormônio-Dependentes/cirurgia , Neoplasias Hormônio-Dependentes/terapia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/psicologia , Roma , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/psicologia , Neoplasias de Mama Triplo Negativas/cirurgia , Neoplasias de Mama Triplo Negativas/terapia
12.
Am J Surg Pathol ; 44(8): 1005-1016, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32452870

RESUMO

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma/patologia , Mucinas/análise , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma/química , Carcinoma/epidemiologia , Carcinoma/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/química , Neoplasias Císticas, Mucinosas e Serosas/epidemiologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , América do Norte , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Sudoríparas/química , Neoplasias das Glândulas Sudoríparas/epidemiologia , Neoplasias das Glândulas Sudoríparas/terapia
13.
Hum Cell ; 33(3): 790-800, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32304027

RESUMO

Anterior gradient 2 (AGR2) was proved to modulate cancer progression. However, the role of AGR2 on endometrial cancer was not established. Here, we investigated the effects of AGR2 expression on endometrial cancer and explored the regulation mechanism. In the study, we found that AGR2 was overexpressed in tumor tissues of 30 endometrial cancer patients. A high level of AGR2 promoted endometrial cancer cells proliferation, migration and invasion. AGR2 induced the expression of lactate dehydrogenase A (LDHA), phosphoglycerate kinase 1 (PGK1), kallikrein 2 (HK2), and enolase 1-α (ENO1), glucose uptake and lactate production. AGR2 could bind to MUC1 and induce MUC1 and hypoxia-inducible factor 1α (HIF-1α). The inhibition effects of AGR2 knockdown on cells proliferation, migration and invasion ability were abolished by the overexpression of MUC1. Besides, the overexpression of MUC1 also reversed the inhibition effects of AGR2 knockdown on the expression of LDHA, HK2, PGK1 and ENO1, glucose uptake and lactate production. AGR2 knockdown inhibited tumor growth, the levels of Ki-67, MUC1, HIF-1α and glycolysis. In conclusion, AGR2 was overexpressed in endometrial cancer and AGR2-induced glucose metabolism facilitated the progression of endometrial carcinoma via the MUC1/HIF-1α pathway. AGR2 may be an effective therapeutic target for endometrial carcinoma.


Assuntos
Carcinoma/genética , Carcinoma/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Glucose/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mucina-1/genética , Mucina-1/metabolismo , Mucoproteínas/fisiologia , Proteínas Oncogênicas/fisiologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma/terapia , Movimento Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/terapia , Feminino , Expressão Gênica , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Terapia de Alvo Molecular , Mucoproteínas/genética , Mucoproteínas/metabolismo , Invasividade Neoplásica/genética , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Fosfoglicerato Quinase/genética , Fosfoglicerato Quinase/metabolismo , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
14.
Am J Surg Pathol ; 44(5): 649-656, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32294063

RESUMO

Mismatch repair deficiency (MMRD) is involved in the initiation of both hereditary and sporadic tumors. MMRD has been extensively studied in colorectal cancer and endometrial cancer, but not so in other tumors, such as ovarian carcinoma. We have determined the expression of mismatch repair proteins in a large cohort of 502 early-stage epithelial ovarian carcinoma entailing all the 5 main subtypes: high-grade serous carcinoma, endometrioid ovarian carcinoma (EOC), clear cell carcinoma (CCC), mucinous carcinoma, and low-grade serous carcinoma. We studied the association of MMRD with clinicopathologic and immunohistochemical features, including tumor-infiltrating lymphocytes in EOC, the histologic type in which MMRD is most frequent. In addition, MLH1 promoter methylation status and massive parallel sequencing were used to evaluate the proportion of sporadic and Lynch syndrome-associated tumors, and the most frequently mutated genes in MMRD EOCs. MMRD occurred only in endometriosis-associated histologic types, and it was much more frequent in EOC (18%) than in CCC (2%). The most frequent immunohistochemical pattern was loss of MLH1/PMS2, and in this group, 80% of the cases were sporadic and secondary to MLH1 promoter hypermethylation. The presence of somatic mutations in mismatch repair genes was the other mechanism of MMRD in sporadic tumors. In this series, the minimum estimated frequency of Lynch syndrome was 35% and it was due to germline mutations in MLH1, MSH2, and MSH6. ARID1A, PTEN, KTM2B, and PIK3CA were the most common mutated genes in this series. Interestingly, possible actionable mutations in ERRB2 were found in 5 tumors, but no TP53 mutations were detected. MMRD was associated with younger age and increased tumor-infiltrating lymphocytes. Universal screening in EOC and mixed EOC/CCC is recommended for the high frequency of MMRD detected; however, for CCC, additional clinical and pathologic criteria should be evaluated to help select cases for analysis.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/genética , Neoplasias Ovarianas/genética , Fatores Etários , Biomarcadores Tumorais/deficiência , Carcinoma/mortalidade , Carcinoma/patologia , Carcinoma/terapia , Neoplasias Colorretais Hereditárias sem Polipose/mortalidade , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Metilação de DNA , Análise Mutacional de DNA , Enzimas Reparadoras do DNA/deficiência , Progressão da Doença , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Fenótipo , Intervalo Livre de Progressão , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Espanha , Fatores de Tempo
15.
Hum Cell ; 33(3): 768-779, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32166565

RESUMO

Non-catalytic region of tyrosine kinase adaptor protein 1 (Nck1) is crucial for the progression of cancers. However, little is known on the role of Nck1 in the progression of ovarian carcinoma (OC). Here, we show that Nck1 expression is up-regulated in 176 OC tissues, compared with non-carcinoma ovarian tissues, and the up-regulated Nck1 expression is associated with the aggressiveness of OC and shorter overall and disease-free survival in this population. Higher Nck1 expression was an independent risk factor for poor prognosis of OC. Furthermore, Nck1 silencing by short hairpin RNA (shRNA) technology significantly inhibited the proliferation, migration and invasion of OC cells in vitro and the growth and metastasis of implanted OC tumors in vivo. Human kinase phosphorylation array indicated that Nck1 silencing significantly reduced the relative levels of 11 kinase expression and phosphorylation in OC cells, particularly for decreased levels of p70S6 kinase (p70S6K) and protein kinase B (AKT) expression in SKOV3 cells. Actually, Nck1 silencing significantly decreased PI3K and AKT expression, and reduced AKT and p70S6K phosphorylation while Nck1 over-expression had opposite effects in OC cells. Therefore, our data indicate that Nck1 promotes the progression of OC by enhancing the PI3k/AKT/p70S6K signaling in OC. Our findings suggest that Nck1 expression may be valuable for evaluating the prognosis of OC and as a target for design of new therapies for OC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Carcinoma/genética , Proteínas Oncogênicas/fisiologia , Neoplasias Ovarianas/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/fisiologia , Carcinoma/terapia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Terapia de Alvo Molecular , Neoplasias Ovarianas/terapia , Prognóstico , Transdução de Sinais/genética
17.
Can J Surg ; 63(1): E71-E79, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32080999

RESUMO

Background: Peritoneal recurrences after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancers are frequent. This study aimed to evaluate the safety, technical feasibility and perioperative and long-term outcomes of repeat CRS/HIPEC in patients with recurrent peritoneal carcinomatosis of colorectal and appendiceal origin. Methods: Data were collected from patients treated from 2000 to 2016 for recurrent peritoneal carcinomatosis from appendiceal or colorectal cancer with CRS/HIPEC at 2 specialist centres. Data on demographics, procedure details, morbidity and survival were recorded. Analyses compared the iterations of CRS/HIPEC to assess the safety and effectiveness of repeat surgery. Results: Of all patients who underwent CRS/HIPEC in the 2 centres, 37 patients underwent a repeat procedure. Operative time was similar for the first and second surgeries (412.1 v. 412.5 min, p = 0.74) but patients had a significantly lower peritoneal carcinoma index score with the second surgery (21.8 in the first iteration v. 9.53 in the second iteration, p < 0.001) and significantly less blood loss (1762 mL in the first iteration v. 790 mL in the second iteration, p = 0.001). There was a nonsignificant decrease in grade III­IV complications and there was no 30-day mortality associated with repeat procedures. For patients with colorectal cancer, median disease-free survival was 9.6 months and median overall survival was 40 months. For patients with appendiceal cancer, median disease-free survival was 15 months and overall survival was 64.4 months. Conclusion: Repeat CRS/HIPEC procedures for recurrent appendiceal and colorectal peritoneal carcinomatosis are safe in well-selected patients, without increased morbidity or mortality, and they are associated with significant long-term survival, particularly for patients with appendiceal cancers. These results support the use of repeat CRS/HIPEC in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Apêndice/terapia , Carcinoma/terapia , Neoplasias Colorretais/terapia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Recidiva Local de Neoplasia/terapia , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Peritoneais/terapia , Reoperação , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Apêndice/mortalidade , Neoplasias do Apêndice/patologia , Canadá/epidemiologia , Carcinoma/mortalidade , Carcinoma/secundário , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Terapia Combinada , Estudos Transversais , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Reoperação/efeitos adversos , Reoperação/mortalidade , Estudos Retrospectivos
18.
Sci Rep ; 10(1): 2489, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051492

RESUMO

Neoadjuvant chemotherapy (NAC) combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy (CC) will be the new standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) patients. However, many patients fail to receive CC for multiple reasons. We aimed to investigate long-term survival outcomes and toxicities in these patients with NPC treated with additional NAC plus concurrent chemoradiotherapy (CCRT) or IMRT alone. In total, 1,378 previously untreated, newly diagnosed locoregionally advanced NPC patients receiving NAC plus IMRT with or without CC were retrospectively reviewed. We used a propensity score-matched (PSM) method with 1:1 matching to identify paired patients according to various covariates. Survival outcomes and toxicities were compared between the two groups. In total, 288 pairs were identified. With a median follow-up of 86 (range: 8-110) months, the estimated 5-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival rates in patients treated with NAC plus CCRT vs. NAC plus IMRT alone were 96.1% vs. 94.7% (P = 0.201), 93.7% vs. 89.8% (P = 0.129), 91.3% vs. 85.1% (P = 0.024), and 93.0% vs. 90.6% (P = 0.362), respectively. Multivariate analysis showed that CC omission was a prognostic factor for worse PFS. In a subgroup analysis, PFS did not differ significantly between two groups of female patients or aged <60 years or stage T1-2 or stage N0-1 disease. However, fewer acute complications were observed in the NAC plus IMRT alone group. NAC with IMRT alone confers similar survival rates and less acute toxicities. Specifically, NAC plus IMRT alone may be enough for female patients <60 years with stage T1-2 or stage N0-1. However, a prospective randomised trial is needed to validate these results.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/terapia , Neoplasias Nasofaríngeas/terapia , Terapia Neoadjuvante , Radioterapia de Intensidade Modulada , Adolescente , Adulto , Idoso , Antineoplásicos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Análise de Sobrevida
19.
Hum Pathol ; 98: 56-63, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017945

RESUMO

The expression frequency and distribution of glypican-3 (GPC3) was retrospectively assessed by immunohistochemistry in 316 accurately phenotyped ovarian clear cell carcinoma (OCCC) specimens from Canadian patients. The study aimed to evaluate the prevalence of this biomarker in OCCC in a mixed-ethnicity Canadian population and to evaluate associations of GPC3 expression with clinicopathological parameters. Tissue microarrays with napsin A or HNF1ß positive and WT1-negative OCCC specimens were evaluated using a GPC3 antibody clone 1G12. Membranous, cytoplasmic, and Golgi pattern GPC3 expression was noted in 184 of 316 (58.2%) cases; 63 of 316 (20%) cases showed high GPC3 expression (>50% of tumor cells were positive). GPC3 expression was not associated with age, stage, and residual disease after primary surgery. High GPC3 expression did not correlate with a specific morphological pattern or the presence of endometriosis. Furthermore, GPC3 expression was not significantly associated with survival in the entire cohort. Statistically significant association of high GPC3 expression was noted with higher body mass index, napsin A positivity, estrogen receptor (ER) negativity, and ARID1A retention. In a stratified analysis by ARID1A status, high GPC3 expression was significantly associated with unfavorable outcomes in cases with loss of ARID1A (n=10; log rank p=0.0048). Women diagnosed with OCCC and high GPC3 expression were also more likely to receive adjuvant chemotherapy. Considering the tumor-specific membranous expression of GPC3 in 58% of cases and high interobserver reproducibility, GPC3 immunohistochemistry is a robust predictive test for inclusion in clinical trials for GPC3-targeted therapies for OCCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma/química , Glipicanas/análise , Neoplasias Ovarianas/química , Canadá , Carcinoma/imunologia , Carcinoma/patologia , Carcinoma/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia , Pessoa de Meia-Idade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise Serial de Tecidos , Resultado do Tratamento , Regulação para Cima
20.
Medicine (Baltimore) ; 99(5): e18738, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000377

RESUMO

BACKGROUND: To compare the clinical outcomes of radical hysterectomy (RH) with chemoradiotherapy (CRT) in women with stage IB2-IIA cervical cancer. METHODS: Based on articles published up to December 2017, a literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese National Knowledge Infrastructure (CNKI) databases was conducted to identify eligible studies. Overall survival (OS), progression-free survival (PFS) with hazard ratios (HRs), and toxicities with odds ratios (ORs) were analyzed. RESULTS: In total, 7 studies comprising 687 patients were identified for this meta-analysis. RH showed a significant trend toward improved survival outcomes compared with those of CRT, regardless of OS (HR = 0.49, 95% confidence interval [CI] 0.36-0.67, P < .001); or PFS (1.61, 95% CI 1.15-2.26, P = .005) for IB2-IIA cervical cancer. Subgroup analysis revealed that stage IB2 cervical cancer patients obtained better OS (HR = 0.36, 95% CI 0.23-0.56, P < .001; heterogeneity: P = .32, I = 13%). However, a higher incidence of grade 3/4 genitourinary abnormalities was evident with RH (OR = 2.3, 95% CI 1.42-3.87, P = .021). CONCLUSION: Our study suggested that RH had distinct advantages over CRT for carcinoma of the uterine cervix with FIGO stage IB2-IIA, especially for IB2 cervical cancer.


Assuntos
Carcinoma/terapia , Quimiorradioterapia , Histerectomia , Neoplasias do Colo do Útero/terapia , Feminino , Humanos
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