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1.
Histopathology ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985086

RESUMO

AIMS: We sought to determine Non-terminal respiratory unit (TRU) type adenocarcinoma of lung with invasive mucinous adenocarcinoma (IMA) morphology shows gastric differentiation. METHODS AND RESULTS: We reviewed whole section images of 489 cases of lung adenocarcinoma from the Cancer Genome Atlas (TCGA). TCGA data were classified into 426 of TRU type adenocarcinoma, 49 of IMA, and 14 of unclassifiable. Their RNA sequencing data was analyzed by DESeq2 and WGCNA R packages. Gene expression in patients' samples were measured by NanoString assay. Overexpression of genes including REG4, TFF2, MUCL3, FER1L6, B3GALT5, ANXA10, and so on was observed by TCGA analysis in IMA compared to TRU type adenocarcinoma. Many of these genes are those expressed in normal gastric glands and selected for NanoString experiment on 14 IMA and 10 TRU type adenocarcinoma cases. The expression of genes including ANXA10, FER1L6, HNF4a, MUC5AC, REG4, TFF1, TFF2, and VSIGI was increased > 15 fold in IMA. Immunohistochemistry of ANXA10, TFF2, and FER1L6 performed on 31 IMA and 135 TRU type adenocarcinomas showed their predominant expression in IMA while they are not in TRU type adenocarcinoma. CONCLUSION: Our results showed the level of genes expressed in stomach mucosa were increased in IMA compared to TRU type adenocarcinoma, supporting gastric differentiation of IMA. This finding may help to understand the pathogenesis of IMA and find therapeutic targets.

2.
Histopathology ; 73(5): 758-766, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29968390

RESUMO

AIMS: Since Xp11.2 translocation-associated renal cell carcinoma (TRCC) was first recognised, its morphological features and the clinical significance of TFE3 expression, frequency of gene translocation and diagnostic criteria have been the subject of limited studies. The present retrospective analysis aimed to evaluate the correlation between TFE3 immunoreactivity and its gene translocation status using fluorescence in-situ hybridisation (FISH) and determine how TFE3 translocation and expression affect patient prognosis differently. METHODS AND RESULTS: We enrolled 303 consecutive renal cell carcinoma cases. Immunohistochemical staining for TFE3 was performed in 303 cases, and FISH analysis was performed for molecular testing. The TCGA data set of renal cell carcinoma was evaluated to validate TFE3 expression and survival analysis. TFE3 expression was associated significantly with the nested alveolar pattern, papillary pattern, eosinophilic cytoplasm, voluminous expansile cytoplasm, nuclear grade, tumour necrosis, sarcomatoid pattern and picket fence appearance. FISH analysis showed break-apart signals in 26 of 32 (81.25%) cases expressing strong or moderate nuclear TFE3 immunoreactivity. Thirteen of 56 samples that showed no or weak TFE3 expression with morphologically suspicious cases were translocation-positive in the FISH assay. The TFE3-translocation group (harbouring TFE3 translocation regardless of TFE3 expression) showed the poorest progression-free survival (PFS), and the TFE3-expressing group (expressing TFE3 but negative for translocation) was correlated significantly with decreased PFS. CONCLUSION: Increased TFE3 expression in RCC was associated with poor PFS regardless of the gene translocation status. Moreover, morphological analysis should help to select candidates who would benefit from TFE3 staining and FISH analysis.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Translocação Genética
3.
World J Surg Oncol ; 15(1): 72, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28351362

RESUMO

BACKGROUND: Brenner tumors almost always develop in the ovary. Exceptionally, extraovarian Brenner tumors have been reported in the lower abdomen or pelvic organs. Here, we introduce a peculiar case of an extraovarian Brenner tumor arising in the omentum. CASE PRESENTATION: A 43-year-old woman presented with a palpable abdominal mass. Computed tomography (CT) scan revealed a 9.0-cm solid mass in the omentum. The tumor was not associated with pelvic structures, including the ovaries. It was excised under the clinical impression of an extragastrointestinal stromal tumor or neurogenic tumor. Grossly, the mass was a well-circumscribed solid tumor, with yellow-tan cut surface and minute cystic spaces. Microscopically, the tumor showed well-defined epithelial nests with variable cystic changes embedded in an abundant fibrous stroma. The cells within the nests were reminiscent of benign urothelial cells in that they had oval, frequently grooved nuclei. The epithelial cells focally showed a gradual transition into the surrounding stromal cells with short spindled features. The urothelium-like cells were positive for pancytokeratin, WT-1, p63, CK7, uroplakin-III, and GATA-3 but were negative for CD34, CD10, CK20, c-KIT, DOG-1, PAX-8, and calretinin. Morphological and immunohistochemical features of the tumor were the same as an ovarian Brenner tumor, and so it was diagnosed as an extraovarian Brenner tumor. CONCLUSIONS: Although the location of the tumor was very unusual, we could diagnose the tumor as an extraovarian Brenner tumor on the basis of the histologic and immunohistochemical findings. This is the first case of extraovarian Brenner tumor arising in the omentum near the stomach ever reported in the English literature.


Assuntos
Tumor de Brenner/patologia , Omento/patologia , Neoplasias Ovarianas/patologia , Células Estromais/patologia , Adulto , Tumor de Brenner/cirurgia , Feminino , Humanos , Omento/cirurgia , Neoplasias Ovarianas/cirurgia , Prognóstico
4.
Oncol Lett ; 12(2): 1287-1292, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27446428

RESUMO

Leiomyomas and schwannomas of the gastrointestinal tract (GIT) are mainly comprised of spindle-shaped tumor cells and should always be differentiated from gastrointestinal stromal tumors (GISTs). Mast/stem cell growth factor receptor Kit (KIT) and discovered on GIST-1 (DOG1) are well-known diagnostic markers for the detection of a GIST by immunohistochemical staining. The aim of the present study was to assess the prevalence and significance of spindle cell tumors of the GIT with KIT- or DOG1-positive spindle-shaped cells, presumed to be interstitial cells of Cajal (ICCs), other than GISTs. A total of 71 leiomyomas and 35 schwannomas were examined and clinicopathological information was obtained. KIT and DOG1 immunostaining was performed to determine the proportions of positive cells. Mutation screening of KIT exons 9, 11, 13 and 17, and platelet-derived growth factor receptor α (PDGFRA) exons 12 and 18 was performed in cases with a relatively high proportion of either KIT- or DOG1-positive cells. The frequency of leiomyomas and schwannomas with KIT- and DOG1-positive ICCs was 35.2% (25/71 cases) and 5.7% (2/35 cases), respectively. Among the esophageal leiomyomas with KIT- and DOG-positive ICCs (14/25; 56.0%), 5 leiomyomas involved the muscularis mucosa and 9 leiomyomas involved the muscularis propria. All gastric leiomyomas with KIT- and DOG1-positive ICCs (11/25; 44%) involved the muscularis propria. All schwannomas with an increased proportion of KIT- or DOG1-positive ICCs were of gastric origin. No KIT or PDGFRA mutations were detected in 7 leiomyomas and 2 schwannomas. In conclusion, the majority of leiomyomas and the minority of schwannomas in the GIT had a significant portion of KIT- and DOG1-positive cells. All of the tumors were located in the upper GIT, and could be present in the muscularis propria or muscularis mucosa. The tumors represented a non-neoplastic proliferation of KIT- and DOG1-positive cells in the GIT. Careful evaluation of KIT- or DOG1-positive cells in spindle cell tumors of the GIT can assist in forming the correct diagnosis by differentiation from a GIST.

5.
World J Gastroenterol ; 22(15): 4020-6, 2016 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-27099445

RESUMO

AIM: To predict the rate of lymph node (LN) metastasis in diffuse- and mixed-type early gastric cancers (EGC) for guidelines of the treatment. METHODS: We reviewed 550 cases of EGC with diffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type (diffuse > intestinal type), mixed-predominantly intestinal type (intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components. RESULTS: LN metastasis was observed in 12.9% (71/550) of early gastric cancers cases [15/288 mucosal EGCs (5.2%) and 56/262 submucosal EGCs (21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis (20.2%) than cases of pure diffuse type (9.3%) and predominantly intestinal type (12.2%) histology. We measured the dimensions of each component (intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not. CONCLUSION: We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment.


Assuntos
Carcinoma de Células em Anel de Sinete/secundário , Diferenciação Celular , Neoplasias Complexas Mistas/patologia , Neoplasias Gástricas/patologia , Biópsia , Carcinoma de Células em Anel de Sinete/cirurgia , Feminino , Gastrectomia/métodos , Gastroscopia , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Complexas Mistas/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/cirurgia , Carga Tumoral
6.
Oncotarget ; 7(16): 21454-68, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-26894977

RESUMO

Gastric adenocarcinoma is a common form of cancer associated with a poor prognosis. We analyzed microarray profiling data from 48 patients with gastric adenocarcinoma to characterize gastric cancer subtypes and identify biomarkers associated with prognosis. We identified two major subtypes of gastric adenocarcinoma differentially associated with overall survival (P = 0.025). Genes that were differentially expressed were identified using specific criteria (P < 0.001 and >1.5-fold); expression of 294 and 116 genes was enriched in good and poor prognosis subtypes, respectively. Genes related to translational elongation and cell cycle were upregulated in the poor prognosis group. Of these genes, upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. PSMB8 or PBK knockdown had no effect on gastric cancer cell proliferation but suppressed cell migration and invasion, respectively. Furthermore, immunohistochemistry analysis of 385 gastric cancer patients revealed that increased nuclear expression of PSMB8 and PBK was correlated with depth of invasion, lymph node metastasis, and lower survival rates. Taken together, two gastric adenocarcinoma subtypes were predictive of prognosis. PSMB8 and PBK were predictive of gastric cancer prognosis and could be potential gastric cancer subtype-specific biomarkers.


Assuntos
Biomarcadores Tumorais/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Complexo de Endopeptidases do Proteassoma/genética , Neoplasias Gástricas/genética , Idoso , Biomarcadores Tumorais/metabolismo , Western Blotting , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Prognóstico , Complexo de Endopeptidases do Proteassoma/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Regulação para Cima
8.
Korean J Pathol ; 48(5): 366-70, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25366072

RESUMO

It is difficult to distinguish nodular fasciitis (NF) from other neoplasm of the parotid gland, especially pleomorphic adenoma (PA) by fine needle aspiration cytology. A 39-year-old female noticed a mass in the parotid region. The aspirate material showed cohesive parts composed of the cells that had oval or spindle-shaped nuclei and relatively abundant cytoplasm and some cells with plasmacytoid features. The background substance was fibromyxoid. PA was diagnosed based on the cytologic findings. Subsequently, parotidectomy was performed and NF was diagnosed based on histologic and immunohistochemical findings. NF in the parotid region is rare and may be misdiagnosed as other benign or malignant tumors of the parotid gland. The clinical history of rapid growth and the presence of mitoses and inflammatory cells help to distinguish NF from PA. In addition, immunohistochemical stains for smooth muscle actin and CD68 are useful to confirm the diagnosis of NF.

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