ABSTRACT
Methylation of cysteine dioxygenase type 1 (CDO1) gene, a tumor suppressor gene, has been studied in various cancers; however, there is no information regarding Barrett esophagus cancer. In this study, the clinical significance of CDO1 methylation in Barrett esophagus adenocarcinoma (BEA) was clarified. CDO1 gene promoter methylation was analyzed for DNA from the patient's specimens using quantitative methylation-specific polymerase chain reaction. Thirty-eight BEA patients who underwent resection were identified between 2000 and 2014. Hypermethylation of CDO1 gene was demonstrated to be frequently recognized even at early stage in BEA by quantitative methylation-specific polymerase chain reaction. In BEA, there is a robust prognostic difference between stage I and stage II/III/IV with regard to 5-year relapse-free survival (P = 0.0016) and 5-year overall survival (P = 0.0024), and the tumor size separated by 7 cm was also a prognostic factor. There was significant difference in CDO1 gene methylation according to the tumor size (P = 0.036). BEA patients with CDO1 gene methylation were shown marginally significantly poorer prognosis (P = 0.054) than otherwise patients. In conclusion, higher CDO1 gene methylation was seen in BEA at earlier stage than in squamous cell carcinoma, and it may account for aggressive phenotype of BEA.
Subject(s)
Adenocarcinoma/genetics , Barrett Esophagus/genetics , Cysteine Dioxygenase/genetics , DNA Methylation/genetics , Esophageal Neoplasms/genetics , Genetic Predisposition to Disease/epidemiology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Barrett Esophagus/pathology , Barrett Esophagus/surgery , Cell Transformation, Neoplastic/genetics , Cohort Studies , Disease-Free Survival , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagectomy/mortality , Esophagoscopy/methods , Female , Humans , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Polymerase Chain Reaction/methods , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival AnalysisABSTRACT
BACKGROUND: Peritoneal lavage cytology cancer-positive (CY1) is a critical prognostic factor and is taken as representing stage IV in gastric cancer. There is no consensus treatment strategy for CY1-gastric cancer, and the detailed clinicopathological features remain obscure. PATIENTS AND METHODS: Among 790 gastric cancer patients between 2005 and 2009, 52 cases of CY1 were identified (6.6%). A multivariate prognostic model was applied to the univariate prognostic factors to identify independent prognostic factors and factors associated with long-term survival in CY1-gastric cancer. RESULTS: (1) Five-year overall survival (OS) was 17.6% in CY1-gastric cancer as compared with 93.9% in CYX and 77.7% in CY0 (77.7%), where tumors with pT2 or beyond were included in 11% of CYX, 73% of CY0, and 98% of CY1 cases. (2) On univariate analysis, factors associated with a negative prognosis were the presence of peritoneal dissemination (p = 0.029) and high preoperative serum albumin (p = 0.011) in CY1-gastric cancer. The multivariate Cox proportional hazards and logistic regression model using propensity score identified preoperative albumin as a critical independent prognostic indicator. (3) Long-term survivors were identified and, were often characterized by long-term postoperative adjuvant treatment. CONCLUSION: Reduced preoperative serum albumin and absence of peritoneal dissemination may be predictive factors for long-term survival in patients with advanced gastric cancer with positive cytology test. Long-term postoperative adjuvant therapy might improve survival of patients with CY1.
Subject(s)
Hypoalbuminemia/blood , Peritoneal Neoplasms/secondary , Serum Albumin/metabolism , Stomach Neoplasms/blood , Stomach Neoplasms/mortality , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Disease-Free Survival , Docetaxel , Drug Combinations , Female , Gastrectomy , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Oxonic Acid/administration & dosage , Peritoneal Lavage , Peritoneal Neoplasms/mortality , Preoperative Period , Prognosis , Proportional Hazards Models , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Taxoids/administration & dosage , Tegafur/administration & dosageABSTRACT
Three neonates born to three mothers with primary myxedema who have thyrotropin-binding inhibitor immunoglobulin (TBII) were continually examined after birth. One neonate showed a high TSH level in mass-screening for congenital hypothyroidism and developed transient hypothyroidism. Her TBII disappeared at 114 days of age, and she remained euthyroid after discontinuation of thyroxin replacement at 146 days of age. The other two neonates were euthyroid, though they had positive TBII. In three mothers, the doses of IgGs that inhibited 125I-TSH binding to the level of 50% were compared. The potency of IgG from the mother whose neonate developed hypothyroidism was stronger than that of IgG from the other two mothers. And the elevation of cAMP induced by bovine TSH in suspension culture with porcine thyroid follicles was significantly reduced in the presence of IgG from the three mothers when compared with normal IgG. The thyroid-stimulation blocking activity was more potent in the mother whose neonate developed hypothyroidism than in the other two mothers. This study suggests that the thyroid function of neonates born to primary myxedema with blocking type TBII is influenced by the potency of TSH-binding inhibitor and thyroid-stimulation blocking activity of the mother.
