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Colorectal cancer (CRC) is presently the second most prevalent global mortality-inducing cancer. CRC carcinogenesis is a multifactorial process involving internal genetic mutations and the external environment. In addition, non-neoplastic cell activities within tumor microenvironments for CRC development have been established. However, interleukin (IL)-33, secreted by such cell types, plays a pivotal role in cancer progression due to interaction with cellular constituents within the tumor-inflammation microenvironment. IL-33 belongs to the IL-1 cytokine family and acts as binding attachments for the suppressor of tumorigenicity (ST)2 receptor. Therefore, how to coordinate tumor microenvironment, design and optimize treatment strategies suitable for CRC, based on IL-33/ST2 signal is a challenge. Even though it has established influences upon immunity-linked conditions, IL-33 effects on CRC progression and prevention and related mechanisms are still controversial. Our review depicts controversial activities for IL-33/ST2 within carcinogenesis and cancer prevention. Moreover, IL-33/ST2 signaling is a potential therapeutic target for CRC.
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BACKGROUND: Soft tissue perineurioma of the kidney is rare, with only a few reported cases. We report two additional cases with histologic, immunohistochemical and genetic analyses. CASE PRESENTATION: Both tumors were from adults (1 female aged 49 years and 1 male aged 42 years) and grossly had maximum diameters of 6.5 and 10 cm, respectively. The tumors were overall well circumscribed but unencapsulated, with focally entrapped benign native renal tubules in one case; both tumors seemed to arise in the capsular areas. The tumors had histologic and immunohistochemical profiles consistent with soft tissue perineurioma. Fluorescence in situ hybridization analyses demonstrated that the tumors were negative for amplification of MDM2 and rearrangements of ESWR1, FUS, and KMT2A. Targeted next-generation sequencing revealed a low tumor mutation burden and likely pathogenic mutations (CYP2B6 and FLT1 mutations for 1 each). Follow-up data were available for both patients; neither had tumor recurrence or metastasis. CONCLUSIONS: In conclusion, renal perineurioma is rare, usually arises in the capsular areas, and is cured by resection. Low-grade dedifferentiated liposarcoma and low-grade fibromyxoid sarcoma as well as other spindle cell lesions should be considered in the differential diagnosis.
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Neoplasias Renais/diagnóstico , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/diagnóstico , Neoplasias de Bainha Neural/diagnóstico , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Amplificação de Genes , Rearranjo Gênico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Renais/química , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/química , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Neoplasias de Bainha Neural/química , Neoplasias de Bainha Neural/genética , Neoplasias de Bainha Neural/patologia , Valor Preditivo dos TestesRESUMO
BACKGROUND: Urinary bladder lymphangioma is a rare and benign lesion that is often causes symptoms related to irritation and urinary tract obstruction. Because a lymphangioma may resemble a true neoplasm of the urinary bladder clinically, the lesion must be removed for accurate histologic diagnosis and to rule out malignancy. CASE PRESENTATION: We present a case of a 40-year-old female who was evaluated for painless gross hematuria. Clinical and diagnostic work up revealed a sharply defined mass involving the wall and bulging into the cavity on the dome of the bladder. Partial cystectomy was performed and histologic findings were compatible with cavernous lymphangioma. The symptom of hematuria relieved after the procedure and the patient was in good status without evidence of recurrence by cystoscopy at follow-up 6 months later. CONCLUSIONS: Lymphangioma of the urinary bladder is treated with surgical excision and seems to have no recurrence once completely resected, but long-time follow-up may be needed.
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Linfangioma/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Cistectomia , Feminino , Hematúria/etiologia , Humanos , Linfangioma/diagnóstico por imagem , Linfangioma/patologia , Linfangioma/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a superficial fibroblastic tumor characterized by high rate of local recurrence and low metastatic potential. Fibrosarcomatous transformation can rarely arise in DFSP either de novo or as recurrent, which represents a form of tumor progression and carries an increased risk of metastasis over classic DFSP. Cytogenetically, DFSP is characterized by a recurrent unbalanced chromosome translocation t (17;22)(q22;q13), leading to the formation of COL1A1-PDGFB fusion transcript that is present in more than 90% of cases. Alternative fusions involving the PDGFD with partners of COL6A3 or EMILIN2 have recently been documented in less than 2% of cases. Herein, we report a DFSP with fibrosarcomtous morphology harboring a novel TNC-PDGFD fusion. CASE PRESENTATION: A 54-year-old female presented with a slowly growing mass in the right thigh. Excision demonstrated a 2-cm ovoid, well-circumscribed, gray-white, mass. Microscopic examination revealed a partially encapsulated subcutaneous nodule without dermal connection. The neoplasm was composed of cellular and fairly uniform spindle cells with brisk mitoses, arranged in elongated fascicles and herringbone patterns, with focal collagenized stroma. The neoplastic cells were positive for CD34 and smooth muscle actin. Fluorescence in-situ hybridization analyses showed negative for COL1A1-PDGFB fusion as well as NTRK1/2/3 rearrangements. A subsequent RNA sequencing detected an in-frame fusion between exon 15 of TNC and exon 6 of PDGFD. This fusion was further confirmed by nested reverse transcription polymerase chain reaction amplification followed by Sanger sequencing. A diagnosis of fibrosarcomatous DFSP was rendered and the patient was in good status at a follow-up of 12 months after the operation. CONCLUSIONS: We report a fibrosarcomatous DFSP with novel TNC-PDGFD fusion, which adds to the pathologic and genetic spectrum of PDGFD-rearranged DFSP.
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Dermatofibrossarcoma/patologia , Fibrossarcoma/patologia , Neoplasias Cutâneas/patologia , Translocação Genética/genética , Biomarcadores Tumorais/genética , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/genética , Feminino , Fibrossarcoma/diagnóstico , Fibrossarcoma/genética , Rearranjo Gênico/genética , Humanos , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Fator de Crescimento Derivado de Plaquetas/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genéticaRESUMO
To investigate the significance of lymph node micrometastasis in T1N0 early gastric cancer. Lymph node micrometastasis may be a key mechanism in the recurrent T1N0 EGC patients after surgical treatment. It's unknow whether it is safe to leave the lymph nodes with micrometastasis untreated after ESD. A total of 106 T1N0 EGC patients were enrolled in this study. Immunohistochemical technique with CAM5.2 was employed to detect lymph node micrometastasis, and Immunohistochemical with D2-40 was used to detect the lymphatic vessels. Prognostic significance of lymph node micrometastasis and the relationship of lymph nodes micrometastasis with Clinicopathological features were analyzed. Twenty-two of the 106 T1N0 EGC cases were detected with lymph nodes micrometastasis, with the detection rate of 20.8%. The median survival time of the group with positive lymph nodes micrometastasis was lower than that of the group with negative micrometastasis, 48 vs 60 months. The incidence of lymph nodes micrometastasis in submucosal T1N0 EGC was 23.9%, while no micrometastasis was found in the mucosal T1N0 EGC. Of all the 30 cases according with the expanded ESD indications, six patients were found with lymph nodes micrometastasis. The occurrence of lymph node micrometastasis was common in T1N0 EGC. The cases with positive lymph nodes micrometastasis showed a lower median survival time than those with negative micrometastasis. lymph nodes micrometastasis incidence was higher in the submucosal ECG than in the mucosal ECG. lymph nodes micrometastasis was also found in the cases according to the expanded ESD indications.
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Neoplasias Gástricas , Gastrectomia , Humanos , Linfonodos , Metástase Linfática , Micrometástase de Neoplasia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgiaRESUMO
The role of forkhead box O3 (FOXO3) as a tumor suppressor gene and its association with the human lifespan is well documented. However, several studies have indicated that high expression of FOXO3 is also significantly associated with tumorigenesis. The aim of the present study was to determine the clinical significance of FOXO3 in the development and prognosis of hepatocellular carcinoma (HCC). mRNA expression data of FOXO3 from The Cancer Genome Atlas database was analyzed through the UALCAN online tool to compare the expression of FOXO3 between HCC and normal liver tissues. Subsequently, the expression of FOXO3 at the protein level was investigated via immunohistochemical staining of 314 HCC and 150 non-cancerous liver tissue samples. The association between protein expression and clinicopathological parameters was analyzed using the χ2 test, and the effect of FOXO3 expression on survival was assessed via Kaplan-Meier analysis. The expression of FOXO3 mRNA was significantly higher in HCC in comparison with healthy tissues. High FOXO3 protein expression was revealed in 43/150 non-cancerous liver tissues, and in 238/314 HCC samples. A significant association was demonstrated between FOXO3 expression and metastasis, Tumor-Node-Metastasis stage, Edmondson grade, α-fetoprotein level and overall survival. In conclusion, the high expression of FOXO3 predicts a poor prognosis in patients with HCC, indicating this protein as a potential therapeutic target in HCC.
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Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin-related protein (DC-SIGNR) is a transmembrane receptor primarily involved in pathogen recognition by the innate immune system, with particular importance for viral recognition. DC-SIGNR may also be associated with tumorigenesis. The aim of the present study was to investigate the association between DC-SIGNR expression, development of hepatocellular carcinoma (HCC), and clinicopathological features. Immunohistochemistry was used to assess DC-SIGNR protein expression in HCC and paired non-cancerous tissue samples. DC-SIGNR expression was lower in HCC tissues compared with adjacent non-tumor tissue samples. The expression of DC-SIGNR was associated with small tumor size, low Edmondson grade and high patient long term survival rates. Bioinformatics analyses were performed on several datasets to assess the potential function of DC-SIGNR and related genes; the data revealed that DC-SIGNR mRNA expression was lower in HCC tissues compared with non-cancerous controls, and analyses of ten-year survival rates indicated patients with low DC-SIGNR expression exhibited shorter average survival times. In conclusion, decreased DC-SIGNR expression in HCC tissues may be a relevant predictive biomarker of clinical prognosis, in addition to being a viable therapeutic target for HCC treatment.
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BACKGROUND: Citron kinase (CIT) is a protein related to cytokinesis and is an important abscission regulator. However, the relationship between CIT and hepatocellular carcinoma (HCC) is unclear. The aim of this study was to investigate the expression CIT in HCC tissues, and explore the connection between this expression and clinicopathological characteristics of HCC. METHODS: Immunohistochemistry staining on 235 HCC tissues and 96 non-tumorous liver tissues controls was performed to examine the CIT protein expression. We then analyzed the correlation between protein expression and clinicopathological parameters via χ2 tests, and we performed overall survival analyses via the Kaplan-Meier survival approach. Based on the online Oncomine Expression Array and UALCAN databases, we more broadly compared CIT mRNA expression between normal and HCC tissues. Finally, we compared CIT mRNA expression in these databases to protein expression in our study and explored potential sources for any observe differences. RESULTS: Compared to normal tissues, CIT expression was significantly lower in HCC tissues. Low CIT expression was found to be related to gender, tumor size, Edmondson Grade, Microvascular invasion, serum AFP levels and poor overall survival. Based on the online databases, CIT mRNA expression was found to be high in HCC tissues and decreased in normal tissues. We hypothesize that this unexpected result is due to a negative feedback loop whereby low protein CIT levels mediate increased CIT mRNA levels. CONCLUSIONS: Lower CIT protein levels are associated with a poorer prognosis in HCC patients, and lower CIT protein levels may mediate a negative feedback loop leading to increased CIT mRNA levels.
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Corticotropin releasing hormone binding protein (CRHBP) mediates the reaction between corticotropin releasing hormone (CRH) and corticotropin releasing hormone receptors (CRHRs). It is expressed in a number of organs, and the expression of CRHBP is associated with tumorigenesis and cancer progression. The aim of the present study was to investigate CRHBP expression levels in hepatocellular carcinoma (HCC) and its association with patient clinicopathological characteristics as well as prognosis. The expression of CRHBP was examined by immunohistochemistry in 169 HCC tissues and 151 adjacent non-tumorous tissues. The results were validated by western blotting using patient tissues and liver cancer cell lines. The association of CRHBP expression with clinicopathological patient characteristics and survival rate was analyzed statistically. Expression of CRHBP was detected in 142/151 (94.0%) non-tumorous liver tissues, and 84/169 (49.7%) HCC tissues (P<0.001). The expression of CRHBP was negatively associated with tumor size (P=0.013), Edmondson Grade (P=0.002), hepatitis B virus antigen (P=0.020), and α-fetoprotein levels (P=0.014). Patients exhibiting low CRHBP expression were associated with shorter survival time compared with those exhibiting high CRHBP expression (P=0.012). The results of western blotting analysis suggest that reduced CRHBP expression is frequently observable in patients with HCC. Low CRHBP expression in HCC tissues may be a predictor of clinical prognosis and a potential therapeutic target for HCC.
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BACKGROUND AND AIM: Hypercalcemia is a potentially fatal and not rare complication of hepatocellular carcinoma (HCC), and its underlying mechanism remains unclear. Parathyroid hormone (PTH) is the most important regulator of the concentrations of calcium and phosphate in blood; parathyroid hormone-related protein (PTHrP) was the most frequent cause of humoral hypercalcemia of malignancy; parathyroid hormone 1 receptor (PTH1R) is the common receptor for PTH and PTHrP. The aim of this study is to investigate the expression of PTH, PTHrP, and PTH1R in HCC tissues, and their relationship with clinical pathological characters in HCC. METHODS: First, a meta-analysis based on online Oncomine Expression Array database was conducted to compare the different mRNA expression of PTH1R, PTH and PTHrP between hepatocellular carcinoma and normal tissues. Then, the protein expression level of differentially expressed gene was examined by immunohistochemistry staining in 223 HCC tissues and 102 non-tumorous liver tissues controls. The relationship between the protein expression and clinicopathological parameters was analyzed by χ2 test, and overall survival analysis was performed using Kaplan-Meier survival analysis. RESULTS: PTH1R mRNA expression was significantly lower in HCC tissues compared with normal tissues, while the expression of PTH and PTHrP showed no significant difference between HCC tissues and normal tissues. High PTH1R protein expression was found in 90/102 cases of adjacent non-tumorous liver tissues, and in 91 of 223 cases of HCC tissues. PTH1R expression was significantly related to tumor size, Edmondson Grade, AFP, and overall survival. CONCLUSIONS: PTH1R may be the major cause of hypercalcemia in HCC, and the decreased PTH1R expression was a poor prognosis in HCC.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Receptor Tipo 1 de Hormônio Paratireóideo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Linhagem Celular Tumoral , Bases de Dados Genéticas , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
This study aims to investigate the prognostic power of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in gastric cancer (GC) and its potential role in cancer development and progression. Data mining results show that CEACAM6 is overexpressed in gastric cancer and is correlated with lymph node metastasis. Subsequently, immunohistochemical staining was performed to determine CEACAM6 protein levels in paraffin gastric tumor specimens. Real-time reverse-transcription-polymerase chain reaction (RT-PCR) was conducted to detect CEACAM6 mRNA levels in fresh GC samples. CEACAM6 protein and mRNA levels were significantly up regulated in GC compared with paired normal mucosa. The IHC staining intensity of CEACAM6 was positively correlated with tumor size, Lauren's classification, vascular invasion, lymph node metastasis, distant metastasis, and TNM stage. CEACAM6 expression was inversely correlated with the five-year survival rate of GC patients. Cox multivariate analysis results demonstrated that the overall survival was independently correlated with CEACAM6 expression. A significant association was observed between CEACAM6 and distant metastases. Network analysis of downstream gene signatures revealed several hub genes such as SRC and DNM1L etc. which may mediating tumor promoting functions of CEACAM6. Further data mining discovered that Tamoxifen etc. could be therapeutic alternatives for gastric patients with CEACAM6 overexpression. Collectively, CEACAM6 overexpression is a common characteristic of GC and is associated with poor 5 year survival rate in GC. Besides, potential molecular mechanisms and treatment options were also provided.
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BACKGROUND AND AIM: ZW10 interacting kinetochore protein 1 (Zwint-1), one of the major kinetochore proteins, is essential for kinetochore function, such as spindle assembly checkpoint function and kinetochore-microtubule attachment. Recently, it has been found over-expressed in some human cancers, including ovarian cancer, bladder cancer, and pulmonary adenocarcinoma. However, few studies of the expression of Zwint-1 in hepatocellular carcinoma (HCC) have been reported. This study is aimed to investigate the expression of Zwint-1 and its relationship with clinical pathological characters in HCC. METHODS: The expression of Zwint-1 protein was analyzed by immunohistochemistry staining on tissue microarrays containing 171 HCC tissues and 187 control non-tumorous liver tissues. The relationships between the Zwint-1 expression and the clinicopathological parameters, and survival analysis were investigated using SPSS software 13.0. RESULTS: Zwint-1 was found uniformly expressed in adjacent non-tumorous liver tissues (184/187, 98.40%), while was significantly decreased in HCC tissues, or even absent (150 of 171, 61.82%, P<0.001). The expression of Zwint-1 was negatively associated with age, tumor size, and Edmondson Grade. Besides, HCC patients with low Zwint-1 expression were also correlated with poor overall survival of the patients. CONCLUSIONS: Decreased expression of Zwint-1 was associated with poor prognosis in HCC.
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The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and critical factor for the efficacy of therapeutic strategies that employ the adenovirus. However, data on CAR expression levels in colorectal cancer are conflicting and its clinical relevance remains to be elucidated. Immunohistochemistry was performed on tissue microarrays containing 251 pairs of colon cancer and adjacent normal tissue samples from Chinese Han patients to assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR expression (40.6% vs. 95.6%; P<0.001) was observed in colorectal cancer samples. The CAR immunopositivity in tumor tissues was not significantly associated with gender, age, tumor size, differentiation, TNM stage, lymph node metastasis or distant metastasis in patients with colon cancer. However, expression of CAR is present in 83.3% of the tumor tissues from patient with colorectal liver metastasis, which was significantly higher than those without liver metastasis (39.6%; P=0.042). At the plasma membrane, CAR was observed in 29.5% normal mucosa samples, which was significantly higher than in colorectal cancer samples (4.0%; P<0.001). In addition, the survival analysis demonstrated that the expression level of CAR has no association with the prognosis of colorectal cancer. CAR expression was observed to be downregulated in colorectal cancer, and it exerts complex effects during colorectal carcinogenesis, potentially depending on the stage of the cancer development and progression. High CAR expression may promote liver metastasis. With regard to oncolytic therapy, CAR expression analysis should be performed prior to adenoviral oncolytic treatment to stratify Chinese Han patients for treatment.
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Neoplasias Colorretais/metabolismo , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/metabolismo , Adenoviridae/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus/genética , Feminino , Expressão Gênica , Terapia Genética , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Transdução Genética , Carga TumoralRESUMO
BACKGROUND: Epidemiologic evidence suggests that chronic inflammation and/or chronic infection is associated with cancer development, and the inflammatory process may play a crucial role in the carcinogenesis and prognosis of colorectal cancer (CRC). Substance P (SP) belongs to the family of tachykinins and acts as an immunomodulator, binding to the neurokinin-1 receptor (NK1R) to initiate tumor cell proliferation, angiogenesis, and migration, steps that are critical for tumor cell invasion and metastasis. It is suggested that SP/NK1R signaling may play an important role in cancer progression and metastasis. However, the exact involvement and significance of SP and NK1R in CRC pathologies remain to be adequately deciphered. PATIENTS AND METHODS: We performed immunohistochemistry staining on tissue microarrays containing 267 pairs of CRC and adjacent normal tissues to evaluate the clinical significance of SP or NK1R in the progression and prognosis of CRC. We also explored the potential correlation between SP and NK1R in CRC development. RESULTS: Expression levels of SP and NK1R were upregulated in CRC compared with their expressions in adjacent normal tissues (P<0.001). High expression of SP in CRC was significantly associated with lymph node metastasis (P<0.001). We also found that high expression of NK1R in CRC was significantly related to TNM (tumor node metastasis) stage (P=0.010) and lymph node metastasis (P=0.019). A high correlation between SP and NK1R expression was also observed (r=0.419, P<0.001). Survival analysis showed that CRC patients with high expression of SP or NK1R have a poor prognosis when compared to patients with low SP or NK1R expression (log rank test, P<0.05). Multivariate analysis using Cox regression model showed that survival was independently correlated with lymph node metastasis, distant metastasis, and SP expression (P<0.05). CONCLUSION: Upregulation of SP-NK1R may play a crucial role in CRC progression. Moreover, SP-NK1R expression may also be used as a predictor for CRC prognosis.
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The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high-grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article outlines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.
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The number of studies reporting lymphoma as a secondary tumor has gradually increased. However, few studies have reported that occurrence of lymphoma as a secondary tumor following treatment for penile carcinoma, particularly cases in which the lymphoma was diagnosed by fine-needle aspiration cytology and flow cytometry. The present study reports the case of a 62-year-old male patient who was troubled with frequent urination and repeated chest tightness for 5 years. The diagnosis upon admission was penile carcinoma. Two months subsequent to the tumor removal surgery, enlarged lymph nodes were extracted from the patient using fine-needle biopsy, to be analyzed using light microscopy and flow cytometry. Smear results indicated a large number of abnormal cells scattered in the right axillary lymph node. Flow cytometry immunophenotyping of fine-needle aspiration samples indicated the increased expression of cluster of differentiation (CD)79a, CD19, CD20, CD38, κ chain and human leukocyte antigen-DR, which supported a diagnosis of B-cell lymphoma. Thus, the patient was diagnosed with B-cell lymphoma based on the results of the fine-needle aspiration biopsy and flow cytometry. The method of diagnosis and causes of therapy-related leukemia are discussed in the present report.
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Mucinous tubular and spindle cell renal cell carcinoma is a rare, recently described variant of renal cell carcinoma characterized by an admixture of cuboidal cells in tubules and sheets of spindle cells, and variable amounts of mucinous stroma. It has been recognized as a distinct entity in the 2004 World Health Organization tumor classification. Since then, several dozen of these tumor have been reported with additional complementary morphologic characteristics, immunohistochemical profile, and molecular genetic features that have further clarified its clinicopathologic aspects. Although originally considered as a low grade renal cell carcinoma on the basis of its bland appearing nuclear features and indolent clinical course, mucinous tubular and spindle cell renal cell carcinoma has currently been proven to be a tumor that has a histological spectrum ranging from low to high grade that includes sarcomatoid differentiation. In this review, we present a detailed summary of the current knowledge regarding the clinicopathologic, immunohistochemical, molecular genetic, and prognostic characteristics, as well as differential diagnoses of mucinous tubular and spindle cell renal cell carcinoma.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/química , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/genética , Diferenciação Celular , Diagnóstico Diferencial , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Neoplasias Renais/química , Neoplasias Renais/classificação , Neoplasias Renais/genética , Técnicas de Diagnóstico Molecular , Gradação de Tumores , Neoplasias Císticas, Mucinosas e Serosas/química , Neoplasias Císticas, Mucinosas e Serosas/classificação , Neoplasias Císticas, Mucinosas e Serosas/genética , Fenótipo , Valor Preditivo dos Testes , Células Estromais/patologiaRESUMO
Liver metastasis is a common event at the advanced stage of pancreatic malignancies. Identification of effective therapeutic targets is crucial for the management of pancreatic cancer patients with liver metastases. In this study, we show that (A) AUTS2 is overexpressed in liver metastases of pancreatic cancer and could be a biomarker for defining cancer subtypes. (B) AUTS2 expression is positively correlated with Docetaxel resistance, TGF-beta pathway activation, HEDGEHOG and WNT signaling pathway. (C) By building an AUTS2 centered protein-drug interaction network, we show that AUTS2 might promote chemotherapeutic resistance and metastasis by exerting its effect on epithelial-mesenchymal transition and WNT signaling pathway. (D) Five drugs that could down regulate the expression of AUTS2 were also suggested. These drugs might help in the treatment of pancreatic cancer patients at the stage of liver metastasis. In summary, our results indicate that AUTS2 is a candidate biomarker for defining liver metastasis of pancreatic cancer and directing personalized therapies.
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Biomarcadores Tumorais/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Proteínas Nucleares/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Animais , Antineoplásicos/uso terapêutico , Proteínas do Citoesqueleto , Estudos de Viabilidade , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Modelos Biológicos , Terapia de Alvo Molecular/métodos , Fatores de TranscriçãoRESUMO
BACKGROUND: Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. METHODS: TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. RESULTS: TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. CONCLUSIONS: TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets.