RESUMO
BACKGROUND: Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. Gastric cancer is characterized by high levels of invasion and metastasis. Increasing attention is being focused on discovering molecular markers for the diagnosis of gastric cancer and for predicting its prognosis. The objective of the present study was to evaluate Nurr1 expression in gastric cancer and to assess its correlation with clinicopathological parameters and prognosis in gastric cancer patients. METHODS: Tissue samples were obtained from 120 gastric cancer patients. We investigated Nurr1 expression in human normal and gastric cancer tissues using real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. We determined the association between Nurr1 and recurrence, prognosis and patient clinicopathological parameters. Univariate and multivariate survival analyses with a Cox's proportional hazards regression model were used to identify independent factors related to recurrence and prognosis. RESULTS: The immunohistochemical, qRT-PCR and western blot analyses revealed that Nurr1 expression was increased in gastric cancer tissues compared with normal gastric tissue (P < 0.05). Nurr1 expression was significantly correlated with the tumor size, depth of tumor invasion, lymph node metastasis, recurrence, and distant metastasis of gastric cancer (P < 0.05). Moreover, Nurr1-high patients also exhibited poorer overall survival (OS) and disease-free survival compared with Nurr1-low patients (P < 0.01). The univariate and multivariate survival analyses suggested that Nurr1 expression (P = 0.011), histology (P = 0.018), depth of tumor invasion (P = 0.037), and presence of lymph node metastasis (P = 0.031) were independent prognostic factors for recurrence. In addition, Nurr1 expression (P = 0.007), depth of tumor invasion (P = 0.014), lymph node metastasis (P = 0.044), distant metastasis (P = 0.023), and recurrence (P = 0.011) were independent prognostic factors of OS in gastric cancer patients. CONCLUSIONS: The Nurr1 protein may be useful as a marker of recurrence, metastasis, and poor prognosis following curative resection in patients with gastric cancer.
Assuntos
Adenocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Linfonodos/patologia , Recidiva Local de Neoplasia/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Neoplasias Gástricas/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Carcinoma de Células em Anel de Sinete/genética , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/patologia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Carga Tumoral , Adulto JovemRESUMO
BACKGROUNDS: A disintegrin and metalloproteinase (ADAM) 17 has been indicated to be an indispensable regulator of cellular events from proliferation to migration. Although prognostic importance of ADAM17 expression has been investigated in several tumours, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. In the current study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after curative gastrectomy. METHODS: The prognostic significance of ADAM17 expression was analysed immunohistochemically in 156 patients with gastric cancer who had undergone curative gastrectomy, and the relationship between its expression and clinicopathological factors was also evaluated. RESULTS: High ADAM17 expression was detected in 79 patients (51 %), whereas low expression was found in 77 cases (49 %). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression (p = 0.032). The median disease-free survival (DFS) time for patients with tumours with high ADAM17 expression was worse than that of patients with tumours with low ADAM17 expression (16.6 vs. 44.2 months, p = 0.004). In addition, patients with low ADAM17 expression had a higher median overall survival (OS) (49.6 vs. 26.9 months, p = 0.019) compared to those with high ADAM17 expression. Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to the already known important clinicopathological prognostic indicator. But the prognostic importance of ADAM17 expression could not be proved by multivariate analysis for OS. CONCLUSIONS: The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively; it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection.
Assuntos
Proteínas ADAM/metabolismo , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma/secundário , Carcinoma de Células em Anel de Sinete/secundário , Gastrectomia/mortalidade , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/patologia , Proteína ADAM17 , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/cirurgia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
PURPOSE: Y-box binding protein 1 (YB-1) expression in cancer cells is closely associated with malignant progression and poor prognosis in various cancers. Recently, we demonstrated that YB-1 expression in cancer cells is an immunomarker for patient prognosis and liver metastasis of gastric cancer (GC), and identified YB-1 as an excellent biomarker of angiogenic and proliferating endothelial cells in cancers. We further explored the expression patterns of YB-1 in gastric vasculature and the relationship with the clinical pathologic characteristics, as well as YB-1 phenotype in cancer cells. METHODS/PATIENTS: Immunohistochemical analysis of YB-1 was performed using 163 surgically resected primary GC specimens. RESULTS: YB-1 expression in cancer cells significantly differed with respect to Lauren type, JGCA classification, vascular invasion (VI), and microvessel density (MVD) of cancers (P = 0.018, P = 0.002, P < 0.001, and P < 0.001, respectively). No correlation was found between cancer-cell YB-1 expression and TNM stage or lymphatic invasion. However, YB-1 expression in vascular endothelial cells significantly correlated with N stage, M stage, TNM stage, and MVD of cancers (P < 0.001, P = 0.013, P < 0.001, and P < 0.001, respectively). Notably, cases with YB-1 expression in cancer vasculature also demonstrated YB-1 expression in cancer cells (P = 0.040). CONCLUSIONS: YB-1 may promote GC development through its function in both cancer cells and cancer vascular cells, and thus represent a potential biomarker in this disease.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células em Anel de Sinete/secundário , Endotélio Vascular/patologia , Neovascularização Patológica/metabolismo , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Proteína 1 de Ligação a Y-Box/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/irrigação sanguínea , Carcinoma de Células em Anel de Sinete/metabolismo , Progressão da Doença , Endotélio Vascular/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neovascularização Patológica/patologia , Prognóstico , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/metabolismoRESUMO
AIMS: Signet-ring cell (SRC) change has not been reported in adenoid cystic carcinoma (ACC). The aim of this study was to describe the clinicopathological and immunohistochemical findings in four cases of ACC with SRCs (ACC-SRC), in which the relative proportion of the SRC component ranged from 25% to 50%. METHODS AND RESULTS: The median age was 58 years (range: 48-81 years), and all patients were women. The involved sites were sinonasal, lip, and submandibular. Two patients developed lung metastasis, and one died of disease 63 months after tumour resection. Neither mucinous nor lipid substances were detected in the SRCs. These showed positive staining for AE1/AE3, cytokeratin 14, and epithelial membrane antigen, which highlighted the intracytoplasmic vacuole borders. The SRC nests were surrounded by myoepithelial cells positive for α-smooth muscle actin and p63. The SRCs showed similar p53 positivity but lower Ki67 and mitotic indices than the conventional component. SRCs were c-Myb-negative. Ultrastructural examination revealed that the intracytoplasmic vacuoles were lumina lined by microvilli. CONCLUSIONS: ACC-SRC is a non-mucin-producing and non-lipid-producing phenomenon, possibly related to disturbed differentiation of ductal/luminal cells. This cellular modification in ACC apparently does not change the biological behaviour of the tumour, but it may cause significant diagnostic problems, particularly in incisional biopsies.