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In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.
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Neoplasias Colorrectales , Genes p53 , Neoplasias Colorrectales/genética , Humanos , Inmunohistoquímica , Mutación , Pronóstico , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVES: To evaluate radiologic and histologic correlations for interstitial lung abnormalities (ILAs) and to investigate radiologic or pathologic features contributing to disease progression and mortality. METHODS: From 268 patients who underwent surgical lung biopsy between January 2004 and April 2019, 45 patients with incidentally detected ILA and normal pulmonary function were retrospectively included. CT features were classified as subpleural fibrotic or non-fibrotic, and changes in ILA over at least 2 years of follow-up were evaluated. Histologic findings were categorized as definite, probable, indeterminate, or alternative diagnosis for usual interstitial pneumonia (UIP) patterns. Overall and progression-free survival were calculated using the Kaplan-Meier method, and the Cox proportional hazard method was used to examine predictors for ILA progression and survival. RESULTS: Among 36 subpleural fibrotic ILA subjects, 25 (69%) showed definite or probable UIP patterns, and 89% (8/9) of subpleural non-fibrotic ILA subjects showed an indeterminate or alternative diagnosis for UIP pattern on histopathology. On the radiologic-pathologic correlation, reticular opacity of fibrotic ILA was correlated with patchy involvement of fibrosis, and ground-glass attenuation of non-fibrotic ILA corresponded to diffuse interstitial thickening. The median progression time of ILA was 54 months, and fibrotic ILA increased the likelihood of progression (hazard ratio, 2.42; p = 0.017). The median survival time of ILA subjects was 123 months, and fibrotic ILA was associated with an increased risk of death (hazard ratio, 9.22; p = 0.025). CONCLUSIONS: Subpleural fibrotic ILAs are associated with pathologic UIP patterns, and it is important to recognize subpleural fibrotic ILA on CT to predict disease progression and mortality. KEY POINTS: ⢠In total, 69% of subpleural fibrotic ILA showed definite or probable UIP patterns, while 11% of subpleural non-fibrotic ILA showed definite or probable UIP patterns. ⢠Subpleural fibrotic ILA was associated with an increased rate of progression (hazard ratio, 2.42; p = 0.017), and the median progression-free time was 40 months. ⢠Subpleural fibrotic ILA had an increased risk of death (hazard ratio, 9.22; p = 0.025), and the median survival time was 86 months.
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Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Humanos , Fibrosis Pulmonar Idiopática/patología , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray. METHODS: We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression. RESULTS: Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients. CONCLUSIONS: Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients.
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Carcinoma de Células Transicionales/mortalidad , Nectinas/fisiología , Proteínas/fisiología , Neoplasias de la Vejiga Urinaria/mortalidad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Oxidative stress induces various intracellular damage, which might be correlated with tumorigenesis. Accumulated oxidative stresses might inactivate protein tyrosine phosphatase (PTP) by oxidizing it, and inducing the phosphorylation of H2AX (γH2AX) in response to DNA damage. METHODS: We evaluated the clinical significance of the expression of oxidized-PTP and γH2AX in 169 gastric carcinomas. RESULTS: Immunohistochemical expression of nuclear oxidized-PTP, cytoplasmic oxidized-PTP, and γH2AX expression were significantly associated with each other, and their expressions predicted shorter survival of gastric carcinoma patients. In multivariate analysis, nuclear oxidized-PTP (overall survival; p < 0.001, relapse-free survival; P < 0.001) was an independent indicator of poor prognosis of gastric carcinoma patients. In addition, co-expression patterns of nuclear oxidized-PTP and γH2AX were independent indicators of poor prognosis of gastric carcinoma patients (overall survival; P < 0.001, relapse-free survival; P < 0.001). CONCLUSIONS: This study suggests that oxidative stress-mediated oxidation of PTP might be involved in the progression of gastric carcinomas. In addition, this study suggests that individual and co-expression pattern of nuclear oxidized-PTP and γH2AX might be used as a prognostic marker of gastric carcinomas.
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Carcinoma/genética , Histonas/genética , Proteínas Tirosina Fosfatasas/genética , Neoplasias Gástricas/genética , Adulto , Anciano , Carcinogénesis/genética , Carcinoma/patología , Daño del ADN/genética , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/genética , Pronóstico , Neoplasias Gástricas/patologíaRESUMEN
CK2α has diverse effects on the tumorigenesis owing to its kinase activity, which phosphorylates various proteins involved in tumorigenesis. We, therefore, investigated the expression and role of CK2α in the phosphorylation of deleted in breast cancer 1 (DBC1) in gastric carcinomas. We used 187 gastric carcinomas and human gastric cancer cells to investigate the roles and relationship between CK2α and DBC1 in gastric carcinomas. Positive expression of CK2α and phospho-DBC1 predicted shorter overall survival and relapse-free survival by univariate analysis. Especially, CK2α expression was an independent prognostic indicator for gastric carcinoma patients. In gastric carcinoma cells, CK2α was bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2α was evidenced by co-immunoprecipitation of CK2α and DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. Inhibition of both CK2α and DBC1 decreased proliferation and invasive activity of cancer cells. Decreased migration and invasive activity was associated with a downregulation of MMP2, MMP9 and the epithelial-mesenchymal transition. A mutation at the phosphorylation site of DBC1 also downregulated the signals related with the epithelial-mesenchymal transition. Our study demonstrated that CK2α is an independent prognostic indicator for gastric carcinoma patients and is involved in tumorigenesis by regulating the phosphorylation of DBC1. In addition, the blocking of CK2α and DBC1 inhibited the proliferation and invasive potential of gastric cancer cells. Therefore, our study suggests that CK2α-DBC1 pathway might be a new therapeutic target for the treatment of gastric carcinoma.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma/enzimología , Quinasa de la Caseína II/fisiología , Neoplasias Gástricas/enzimología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Fosforilación , Pronóstico , Procesamiento Proteico-Postraduccional , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patologíaAsunto(s)
Aneurisma/cirugía , Arterias Bronquiales/anomalías , Arterias Bronquiales/cirugía , Enfermedades Bronquiales/complicaciones , Enfermedades Bronquiales/cirugía , Embolización Terapéutica/efectos adversos , Complicaciones Posoperatorias/etiología , Arterias Bronquiales/fisiopatología , Enfermedades Bronquiales/fisiopatología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient's father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.
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RATIONALE: Adenomatous polyposis (AP) is a genetic disorder characterized by the occurrence of numerous adenomatous polyps in the colon and rectum and can be classified into classical AP and attenuated AP (AAP). AAP is diagnosed when the number of observed adenomas is between 10 and 99. The detection of AAP is significantly increasing mainly due to the improvement of the imaging technique and application of the screening program for colorectal cancer detection. Currently, the germline variations of the APC and MUTYH genes are reported as the main cause of classical AP. However, the underlying genetic basis of AAP is not well understood. In this study, we report 2 cases of AAP with MSH6 variations. PATIENT CONCERNS: Both patients visited the hospital after multiple polyps were detected during colonoscopies conducted as part of their health checkups. DIAGNOSES: The 2 patients were diagnosed with AAP through colonoscopic examination at our hospital. INTERVENTIONS: The 2 received genetic consultation; and, for follow-up purposes, both patients agreed to be tested for an underlying genetic condition through next generation sequencing. And germline MSH6 variations were detected in both AAP patients. OUTCOMES: There was no recurrence for both patients for 3 years follow-up. LESSONS: Minor portion of AAP can cause by genetic mutation in MSH6, and further research is needed.
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Poliposis Adenomatosa del Colon , Proteínas de Unión al ADN , Humanos , Masculino , Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/diagnóstico , Persona de Mediana Edad , Femenino , Proteínas de Unión al ADN/genética , Adulto , Colonoscopía , Mutación de Línea GerminalRESUMEN
ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.
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Neoplasias Pulmonares , Humanos , Interferones/metabolismo , Neoplasias Pulmonares/genética , Sirtuina 1/genéticaRESUMEN
BACKGROUND: Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. METHODS: We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. RESULTS: Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. CONCLUSIONS: This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Hemo-Oxigenasa 1/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Adulto , Anciano , Neoplasias de la Mama/genética , Femenino , Expresión Génica , Hemo-Oxigenasa 1/genética , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Factor de Crecimiento Nervioso/genética , Pronóstico , Adulto JovenRESUMEN
Found in inflammatory zone (FIZZ) 2, also known as resistin-like molecule (RELM)-ß, belongs to a novel cysteine-rich secreted protein family named FIZZ/RELM. Its function is unclear, but a closely related family member, FIZZ1, has profibrotic activities. The human ortholog of rodent FIZZ1 has not been identified, but human FIZZ2 has significant sequence homology to both rodent FIZZ2 (59%) and FIZZ1 (50%). Given the greater homology to rodent FIZZ2, analyzing the role of FIZZ2 in a rodent model of bleomycin-induced pulmonary fibrosis would be of greater potential relevance to human fibrotic lung disease. The results showed that FIZZ2 was highly induced in lungs of rodents with bleomycin-induced pulmonary fibrosis and of human patients with idiopathic pulmonary fibrosis. FIZZ2 expression was induced in rodent and human lung epithelial cells by Th2 cytokines, which was mediated via STAT6 signaling. The FIZZ2 induction in murine lungs was found to be essential for pulmonary fibrosis, as FIZZ2 deficiency significantly suppressed pulmonary fibrosis and associated enhanced extracellular matrix and cytokine gene expression. In vitro analysis indicated that FIZZ2 could stimulate type I collagen and α-smooth muscle actin expression in lung fibroblasts. Furthermore, FIZZ2 was shown to have chemoattractant activity for bone marrow (BM) cells, especially BM-derived CD11c(+) dendritic cells. Notably, lung recruitment of BM-derived cells was impaired in FIZZ2 knockout mice. These findings suggest that FIZZ2 is a Th2-associated multifunctional mediator with potentially important roles in the pathogenesis of fibrotic lung diseases.
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Hormonas Ectópicas/biosíntesis , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/metabolismo , Animales , Células de la Médula Ósea/patología , Movimiento Celular/inmunología , Proliferación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Fibroblastos/patología , Hormonas Ectópicas/genética , Hormonas Ectópicas/fisiología , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Noqueados , Ratones Transgénicos , Miofibroblastos/patología , Fibrosis Pulmonar/patología , Ratas , Ratas Endogámicas F344 , Células Th2/inmunología , Células Th2/metabolismo , Células Th2/patologíaAsunto(s)
Eosinofilia/etiología , Eosinofilia Pulmonar/etiología , Fumar/efectos adversos , Traqueítis/etiología , Enfermedad Aguda , Broncoscopía , Eosinofilia/diagnóstico por imagen , Eosinofilia/tratamiento farmacológico , Eosinofilia/patología , Glucocorticoides/uso terapéutico , Humanos , Masculino , Prednisolona/uso terapéutico , Eosinofilia Pulmonar/diagnóstico por imagen , Eosinofilia Pulmonar/tratamiento farmacológico , Eosinofilia Pulmonar/patología , Radiografía Torácica , Tomografía Computarizada por Rayos X , Traqueítis/diagnóstico por imagen , Traqueítis/tratamiento farmacológico , Traqueítis/patología , Adulto JovenRESUMEN
Myoid angioendothelioma of the spleen is an uncommon, benign vascular tumor that is morphologically characterized by a composite of vascular spaces and stromal cells with myoid feature. Herein, we report a case of the myoid angioendothelioma of the spleen, concurrent with rectal adenocarcinoma. A 41-year-old woman presented with hematochezia for several weeks. Grossly, the rectal mass was a 2.5 × 2-cm ulcerative fungating lesion. The splenic mass was a 2.2 × 2-cm well-circumscribed lesion. Microscopically, the rectal mass was a well-differentiated adenocarcinoma that invaded into the pericolic adipose tissue. The splenic mass was composed of slit-like vascular spaces and fascicles of elongated stromal cells. Vascular endothelial cells were immunopositive for CD31, factor VIII-related antigen, and CD34 but negative for CD8. Stromal cells were immunopositive for smooth muscle actin but negative for desmin.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Hemangioendotelioma/diagnóstico , Hemangioendotelioma/patología , Neoplasias del Recto/patología , Neoplasias del Bazo/diagnóstico , Adenocarcinoma/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Femenino , Hemangioendotelioma/diagnóstico por imagen , Humanos , Hallazgos Incidentales , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Radiografía , Neoplasias del Bazo/patología , Neoplasias del Bazo/secundarioRESUMEN
Primary small cell thyroid carcinomas are extremely rare and there is still debate about their classification as a distinct disease entity. The present case report reports a small cell carcinoma (SCC) combined with poorly differentiated thyroid carcinoma (PDTC) in a 34 year old man. The tumor consisted of ~80% PDTC and ~20% SCC. The PDTC component was positive for cytokeratin and thyroid transcription factor-1 (TTF-1), and negative for calcitonin, chromogranin and synaptophysin. The SCC component was positive for synaptophysin and CD56, and negative for calcitonin, chromogranin and TTF-1. Seven months after thyroid surgery, two new lung nodules were detected. Histologically and immunohistochemically, the lung tumors were similar to the SCC component of the thyroid carcinoma. The mutational status of cancer-related genes was assessed using targeted next-generation sequencing in both the thyroid and lung, which identified similar genetic alterations. The histogenesis of SCC was evaluated through NGS analysis of the two cancer components.
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BACKGROUND: FAM83H has been implicated in cancer progression, and PD1 is an important target for anti-cancer immune checkpoint therapy. Recent studies suggest an association between FAM83H expression and immune infiltration. However, studies on the roles of FAM83H and its relationship with PD1 in breast carcinomas have been limited. METHODS: Immunohistochemical expression of FAM83H and PD1 and their prognostic significance were evaluated in 198 breast carcinomas. RESULTS: The expression of FAM83H in cancer cells was significantly associated with the presence of PD1-positive lymphoid cells within breast carcinoma tissue. Individual and co-expression patterns of nuclear FAM83H and PD1 were significantly associated with shorter survival of breast carcinomas in univariate analysis. In multivariate analysis, the expression of nuclear FAM83H (overall survival, p < 0.001; relapse-free survival, p = 0.003), PD1 (overall survival, p < 0.001; relapse-free survival, p = 0.003), and co-expression patterns of nuclear FAM83H and PD1 (overall survival, p < 0.001; relapse-free survival, p < 0.001) were the independent indicators of overall survival and relapse-free survival of breast carcinoma patients. CONCLUSIONS: This study suggests a close association between FAM83H expression and the infiltration of PD1-positive lymphoid cells in breast carcinomas and their expression as the prognostic indicators for breast carcinoma patients, and further studies are needed to clarify this relationship.
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Stress that impairs endoplasmic reticulum (ER) function leads to an accumulation of unfolded or misfolded proteins in the ER (ER stress) and triggers the unfolded protein response (UPR). Recent studies suggest that ER stress is involved in idiopathic pulmonary fibrosis (IPF). The present study was undertaken to determine the role of ER stress on myofibroblastic differentiation of fibroblasts. Fibroblasts in fibroblastic foci of IPF showed immunoreactivity for GRP78. To determine the role of ER stress on α-smooth muscle actin (α-SMA) and collagen type I expression in fibroblasts, mouse and human lung fibroblasts were treated with TGF-ß1, and expression of ER stress-related proteins, α-SMA, and collagen type I was analyzed by Western blotting. TGF-ß1 significantly increased expression of GRP78, XBP-1, and ATF6α, which was accompanied by increases in α-SMA and collagen type I expression in mouse and human fibroblasts. A chemical chaperone, 4-PBA, suppressed TGF-ß1-induced UPR and α-SMA and collagen type I induction. We also showed that TGF-ß1-induced UPR was mediated through the reactive oxygen species generation. Our study provides the first evidence implicating the UPR in myofibroblastic differentiation during fibrosis. These findings of the role of ER stress and chemical chaperones in pulmonary fibrosis may improve our understanding of the pathogenesis of IPF.
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Diferenciación Celular , Retículo Endoplásmico/metabolismo , Fibroblastos/citología , Pulmón/metabolismo , Animales , Chaperón BiP del Retículo Endoplásmico , Femenino , Humanos , Pulmón/citología , Ratones , Ratones Endogámicos C57BL , Estrés OxidativoRESUMEN
Stress that impairs endoplasmic reticulum (ER) function leads to an accumulation of unfolded or misfolded proteins in the ER (ER stress). Autophagy is a lysosomal pathway involved in the turnover of cellular macromolecules and organelles, which emerging data indicate that ER stress is also a potent inducer of autophagy. ER stress and autophagy are involved in human cancer. We examined the expression of ER stress-related proteins [GRP78 and C/EBP homologous protein (CHOP)] and autophagic proteins (Beclin-1 and LC3) in non-small cell lung carcinomas (NSCLCs), bronchioloalveolar carcinomas (BACs) and atypical adenomatous hyperplasias (AAHs) to understand their role in the NSCLC pathogenesis. The expression of GRP78 and CHOP, Beclin-1 and LC3 were analyzed using immunohistochemistry on tissue sections from 133 NSCLC (69 squamous cell carcinomas, 56 adenocarcinomas (AC) and eight other NSCLCs), 21 BAC and 9 AAH. Expression of GRP78 and Beclin-1 was correlated with low tumor stage (p < 0.001 and p = 0.019, respectively) and longer survival (p = 0.007 and p <0.001, respectively) by Kaplan-Meier analysis. However, CHOP was correlated with high tumor stage (p = 0.038) and shorter survival (p = 0.012). Expression of GRP78 and Beclin-1 was positively correlated (p = 0.006). Our study showed that the expression of GRP78, CHOP, Beclin-1 and LC3 in lung cancer and its relation with clinicopathologic factors and patients survival. These results suggest that GRP78, CHOP and Beclin-1 may play an important role in tumorigenesis of lung AC and may serve as new prognostic indicators for outcome of the patients with NSCLC.
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Autofagia , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Retículo Endoplásmico/metabolismo , Neoplasias Pulmonares/metabolismo , Lesiones Precancerosas/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Beclina-1 , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Chaperón BiP del Retículo Endoplásmico , Proteínas de Choque Térmico/metabolismo , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Proteínas de la Membrana/metabolismo , Invasividad Neoplásica , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/patología , Factor de Transcripción CHOP/metabolismoRESUMEN
BACKGROUND: The objectives of this study were to examine trends in mesothelioma incidence over a decade and to identify histories of asbestos exposure among cases in Korea. METHODS: In 2001, The Korea Occupational Safety and Health Agency organized a nationwide cardiopulmonary pathology group and established a malignant mesothelioma surveillance system covering all general hospitals in Korea. Mesothelioma cases were reported to this surveillance system with information about age, gender, location, occupational history, asbestos exposure environment, date of diagnosis, diagnostic method, histopathologic subtype, occurrence site, and other clinical information. Additionally, an epidemiological survey was conducted using a structured verbal questionnaire to allow further evaluation of asbestos exposures. RESULTS: A total of 399 cases of malignant mesothelioma were reported in the last decade, translating to approximately 40 annual cases, and an annual average incidence rate of 0.83 cases per million. Of the 152 patients interviewed by occupational physicians, 56 had occupational asbestos exposure histories (36.8%). Their occupations and industries included construction (19.7%), automobile repair (5.9%), asbestos textile, shipbuilding and repair, refinery work, boiler making, and asbestos cement work. Another 31 patients had environmental asbestos exposure histories. CONCLUSIONS: Surveillance data indicate that malignant mesothelioma incidence in Korea is, thus far, lower than that of other developed countries, and that construction and environmental asbestos exposure were the main identifiable causes of malignant mesothelioma.
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Amianto/toxicidad , Mesotelioma/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Vigilancia de la Población/métodos , Adolescente , Adulto , Anciano , Estudios Epidemiológicos , Femenino , Encuestas Epidemiológicas , Humanos , Incidencia , Masculino , Mesotelioma/etiología , Persona de Mediana Edad , Enfermedades Profesionales/etiología , República de Corea/epidemiología , Medición de Riesgo/métodos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Hyalinizing trabecular adenoma (HTA) is a rare benign epithelial tumor of the thyroid which shows a prominent trabecular growth pattern and stromal hyalinization. On fine-needle aspiration cytology, HTA is frequently misdiagnosed as either papillary thyroid carcinoma (PTC) or medullary carcinoma. We present both the cytologic and the histopathologic features of HTA in a patient with Hashimoto's thyroiditis. CASE: Cytologically, the tumor cells showed a low nucleocytoplasmic ratio and eccentrically located nuclei, nuclear grooves, and eosinophilic pseudoinclusions. Lymphocyte-dominant inflammatory cells were present in the background, raising the possibility of thyroiditis. Histologically, the tumor was a 0.5 × 0.4 cm-sized mass and showed a trabecular and nested pattern of tumor cells separated by scant hyaline material in the background of Hashimoto's thyroiditis. Tumor cells showed abundant eosinophilic granular cytoplasms, nuclear grooves, and pseudoinclusions, as well as immunoreactivity for MIB-1 on the cell membrane. We diagnosed this lesion as HTA in a patient with Hashimoto's thyroiditis. CONCLUSION: Although distinction of HTA from PTC in the cytologic specimen is difficult, especially in cases associated with Hashimoto's thyroiditis, cohesive cell aggregates with a low nucleocytoplasmic ratio and eccentrically located nuclei may be helpful to consider the possibility of HTA.
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Adenoma/complicaciones , Adenoma/patología , Enfermedad de Hashimoto/complicaciones , Nódulo Tiroideo/complicaciones , Nódulo Tiroideo/patología , Anciano , Biopsia con Aguja Fina , Femenino , HumanosRESUMEN
In the wake of the COVID-19 pandemic, lung disorders have become a major health concern for humans. Allergic asthma is the most prevalent form of asthma, and its treatments target the inflammation process. Despite significant developments in the diagnosis and management of allergic asthma, side effects are a major concern. Additionally, its extreme heterogeneity impedes the efficacy of the majority of treatments. Thus, newer, safer therapeutic substances, such as natural products, are desired. Citrus junos Tanaka has traditionally been utilized as an anti-inflammatory, sedative, antipyretic, and antitoxic substance. In this study, the protective effects of Citrus junos Tanaka peel extract (B215) against lung inflammation were examined, and efforts were made to understand the underlying protective mechanism using an HDM-induced lung inflammation murine model. The administration of B215 reduced immune cell infiltration in the lungs, plasma IgE levels, airway resistance, mucus hypersecretions, and cytokine production. These favorable effects alleviated HDM-induced lung inflammation by modulating the NF-κB signaling pathway. Hence, B215 might be a promising functional food to treat lung inflammation without adverse effects.