High frequency of promoter hypermethylation of the death-associated protein-kinase gene in nasopharyngeal carcinoma and its detection in the peripheral blood of patients.

PURPOSE: Death-associated protein (DAP)-kinase gene is frequently inactivated by promoter hypermethylation in cancer. The aim of this study was to evaluate the promoter methylation status of the DAP-kinase gene in nasopharyngeal carcinoma (NPC). EXPERIMENTAL DESIGN: The methylation status was evaluated by methylation-specific PCR (MSP). Thirty-two NPC biopsy specimens, plasma and buffy coat of 12 patients, 5 NPC cell lines, 3 normal nasopharyngeal biopsy tissues, and 2 normal nasopharyngeal epithelial primary cultures were included in this study. RESULTS: There was no promoter hypermethylation in all 3 normal nasopharyngeal tissues and 2 normal nasopharyngeal primary cultures. Hypermethylation was found in 24 (75%) NPC primary tumor biopsies and 4 (80%) NPC cell lines. Of the 24 patients with hypermethylation of DAP-kinase promoter in the primary tumors, 12 patients had their plasma and buffy coat DNA available for MSP study. Hypermethylated DAP-kinase promoter was detectable in 5 patients in the plasma but not in the buffy coat, 2 patients in the buffy coat but not in the plasma, and 1 patient in both plasma and buffy coat. Four patients had no detectable hypermethylated DAP-kinase promoter in both plasma and buffy coat. Hypermethylation of DAP-kinase promoter was found in both early- and late-stage NPC. CONCLUSIONS: Our results show that hypermethylation of the DAP-kinase promoter is a common early event in NPC. The high frequency of identification of hypermethylated DAP-kinase promoter in plasma and buffy coat of NPC patients illustrates its potential clinical application as tumor marker for the diagnosis and monitoring of treatment result.

Differential gene methylation in undifferentiated nasopharyngeal carcinoma.

Differential gene methylation is observed in a variety of human malignancies. The study of the pattern of methylated genes helps to understand carcinogenesis and to identify potential marker tumor genes for clinical use. The differential methylated genes in undifferentiated nasopharyngeal carcinoma (NPC) of Chinese were studied by methylation-specific polymerase chain reaction (MSP). Methylation status of 11 tumor-associated genes (ARF, caspase-8, CDH1, CDKN2A, CDKN2B, MGMT, MLH1, RASSF1A, THBS1, TP73 and VHL) was studied in 30 primary undifferentiated NPC and paired peripheral blood of 12 patients. The methylation profile of NPC in order of frequency was CDH1 (50%), CDKN2B (50%), THBS1 (50%), RASSF1A (46%), MLH1 (40%), MGMT (28%), CDKN2A (23%), TP73 (20%), caspase-8 (7%), ARF (3%) and VHL (0%). Methylation of at least 1 gene was observed in 93% of primary NPC. Of the 12 patients with at least 1 methylated gene in the primary tumor, all 12 (100%) patients had at least 1 of the methylated gene promoter detectable in their peripheral blood. The results show high frequency of methylation in NPC and the potential of using methylation as peripheral blood tumor marker in screening NPC.

Time course in the relief of nasal blockage after septal and turbinate surgery: a prospective study.

OBJECTIVE: To evaluate prospectively the time course of the change in efficacy of septal and turbinate surgery in relieving nasal obstruction. DESIGN: Interventional study, before-after trial. SETTING: Referral center, institutional practice, hospitalized care. PATIENTS: Thirty-four consecutive patients undergoing septal and turbinate surgery were recruited. Seven patients were unwilling to complete the follow-up after surgery. No patient withdrawal was because of adverse effects. Twenty-five normal subjects with no nasal obstruction were included as control subjects. INTERVENTION: Functional nasal septal and turbinate surgery was performed to relieve nasal obstruction. MAIN OUTCOME MEASURE: Patient assessment of severity of nasal blockage on a 0-mm (no blockage) to 100-mm (maximum blockage) visual analog scale before surgery and at fixed intervals after surgery. RESULTS: The mean nasal blockage scores significantly decreased from the preoperative values at all intervals of follow-up. For the whole group, the nasal blockage score was on average 52% of the preoperative value at the last follow-up. The probability of having at least a 50% reduction in blockage decreased from 73%, to 60%, to 41%, and then to 27% at 3 months, 6 months, 1 year, and 2(1/2) years, respectively. CONCLUSIONS: Improvement in nasal blockage was found in patients after functional septal and turbinate surgery. However, the probability of substantial relief gradually decreased with time. Patients should be followed up after septal and turbinate surgery for possible recurring symptoms.