To determine the chronology of oncogenes in gastric carcinogenesis, we studied oncoproteins of c-Ha/Ki/N-ras, c-erbB-2, and pan-myc in gastric malignant and premalignant lesions of Wistar rats induced by MNNG using im-munohistochemistry. c-ras p21 cytoplasmic staining was seen in 7/23 (30.4%) of gastric adenocarcinomas and found to correlate with the staging of lesions. c-erbB-2 p185 cellular membrance staining was observed in 17/33 (51.5%) and pan-myc p62, in 33/39 (84.6%) chronic atrophic gastritis. The highest positive rate of the concomitant expression of these genes was observed in adenocarcinomas (17.4%). Higher expression level of these three oncoproteins were found in the antral area than those in the fundic area, expression of the three oncogenes was found in adenocarcinomas (17.4%) (P

Objective:To investigate the possibility for human papillomavirus (HPV)infection to be a predictable signal for the carcinogenesis of oral mucosa by comparing the prevalences of HPV in each stage of oral mucosal carcinogenesis and to compare the sensitivity differences of the two methods in de-tecting HPV infection in oral cavity.Methods:The hybrid capture (HC-Ⅱ)was used to detect infection of HPV in 255 samples taken from 1 2 cases of healthy oral mucosa,21 1 cases of patients with pathologi-cal diagnosis and 32 cases of patients with clinical diagnosis.The diagnosed cases included 8 cases of be-nign lesions of the oral mucosa,precancerous lesions [74 cases of oral leukoplakia (OLK)with hyper-plasia and 42 cases of OLK with oral epithelial dysplasia (OED)],91 cases of precancerous condition
[oral lichen planus (OLP)]and 28 cases of oral squamous cell carcinoma (OSCC).And in situ hybri-dization (ISH)was used to detect infection of HPV in 33 cases of OSCC and 76 cases of OLK,including 30 cases of hyperplasia,1 5 cases of mild OED,1 5 cases of moderate OED and 1 6 cases of severe OED. Results:The prevalence of HPV in OLP samples was higher (1 2.1 2%,8/66 )than that of OLK (2.59%,3/1 1 6)(χ2 =4.666,P=0.031 )and OSCC(7.1 4%,2/28,χ2 =0.51 3,P=0.474).The prevalence of HPV in OSCC (7.1 4%,2/28)was higher than that of OLK (2.59%,3/1 1 6),and no significant difference was found.There was only one case of smoke spot and statistical analysis was not carried out.ISH was used to detect type 1 6/1 8 and type 31 /33 HPV DNA in 1 09 cases of oral mucosal lesions in paraffin sections and only one case of OSCC was HPV positive.Thirty-seven cases were detec-ted by HC-Ⅱ and ISH methods at the same time.The same negative results by the two methods were found in 94.6% samples (35/37).In the other two samples,one was OSCC with early infiltration and the other was OLK with hyperplasia,The HC-Ⅱ results were positive while the ISH results were nega-tive.The patients with OLP and HPV testing results were followed up and the average follow-up period was (36.2 ±1 0.5)months.It was found that three of them had a malignant transformation,and the ma-lignant transformation rate of HPV positive patients was 1 2.50% (1 /8),which was higher than that of HPV negative patients (3.45%,2/58),and the difference was not statistically significant,P=0.249. Conclusion:HC-Ⅱ assay was more sensitive in detecting HPV infection of oral mucosal lesions than ISH.The results of this study showed that there was insufficient evidence for taking HPV infection as a predictor of OLK carcinogenesis.Patients suffering from OLP were in a precancerous condition.The pre-valence of HPV in OLP patients of this study was higher than that in OLK and OSCC patients,suggesting that for some reason,OLP patients were susceptible to HPV.HPV testing can be considered as routine in patients with OLP,and HC-Ⅱassay was recommended.And patients with OLP and HPV positive should be followed up regularly.

Objective: To study the association between the AKAP12 promoter methylation and recurrence of hepatocellular carcinoma. Methods: A total of 142 primary liver cancer patients underwent surgery in department of Hepatobiliary surgery in Peking University Cancer Hospital from 2003 to 2009 were selected as subjects in the survey; with the inclusion criteria as hepatocellular carcinoma, no cancer cells were observed in the surgical margin(SM) samples. All patients had neither lymph nor distant metastasis at the time of surgery, and receiving complete follow-up data for at least 3 years. By the end of May 2014, a total of 75 patients had relapsed of whom 71 died and there were no lost. All samples were acquired from the frozen surgical tissues. Genomic DNA was extracted using phenol/chloroform method and performed bisulfite modification following with polymerase chain reaction (PCR). AKAP12 methylation in hepatoma and the corresponding SM samples from 142 patients was determined by denature high-performance liquid chromatography (DHPLC) and bisulfite clone sequencing. Kaplan-Meier and Cox proportion hazard regression model were used to identify the factors related to the survival time. Results: In 142 cases, 125 patients (88.0%) were male and 17 (12.0%) cases were female. The median age was 52.5 years, ranging from 34 years to 76 years. AKAP12 methylation-positive rate was significantly higher in hepatomas than SMs (54.9% vs. 10.2%, P<0.001). Patients with AKAP12 methylation-positive had less risk of the recurrence (HR=0.62, 95%CI: 0.39-0.99); with tumor diameter more than 5 cm (HR=1.53, 95%CI: 1.00-2.50),portal vein invasion(HR=4.53, 95% CI:2.69-7.64) increased the recurrence risk. Moreover, portal vein invasion had a higher risk of death (HR=2.98, 95% CI: 1.73-4.98). Conclusion There was significant association between AKAP12 DNA methylation and low risk of recurrence and long progression-free survival of hepatocellular carcinoma patients.