Study On The Relationship Between The Deletion Of 1p / 19q And The Expression Of VEGF MRNA In Gliomas

Part One: The Expression and Significance Of 1p/19 q LOH in GliomasObjective To detect the frequencies of combining loss of heterozygosity(LOH) of chromosome 1p/19 q in patients with gliomas and investigate the relationship between 1p/19 q LOH and the clinical features including age, sex, side, pathological type and pathological grade. Methods Fluorescence in situ hybridization(FISH) was used to detect 1p/19 q LOH in 128 cases with newly diagnosed gliomas in Affiliated Hospital of Weifang Medical College and Affiliated Hospital of Qingdao University. Clinical data was retrospectively reviewed. The relationship between 1p/19 q LOH and other clinical features including age, sex, side, pathological type and pathological grade was analyzed by Chi-square test. P <0.05 was considered statistically significant. Results Among 128 patients, 71 were male and 57 were female. They aged from 21 to 83, the mean age was 46.2±10.8 years. 72 tumors located in left side, 56 tumors located in right side. 59 cases were astrocytic tumors, 40 cases were oligoastrocytic tumors, 29 cases were oligodendroglial tumors. 4 cases were Grade Ⅰ, 66 cases were Grade Ⅱ, 25 cases were Grade Ⅲ, 33 cases were Grade Ⅳ. 70 cases were low grade gliomas(Grade Ⅰ-Ⅱ), 58 cases were high grade gliomas(Grade Ⅲ-Ⅳ). 1p/19 q LOH in 61 cases(47.66%) was positive, 1p/19 q LOH in 67 cases(52.34%) was negative. There were no statistical differences in sex, age and side between glioma patients with and without 1p/19 q LOH(P>0.05). 1p/19 q LOH, in an descend order, was detected in oligodendroglioma(23/29, 79.31%), oligoastrocytoma(22/40, 55%), astrocytoma(16/59, 27.12%) and low grade glioma(40/70, 57.14%), high grade glioma(21/58, 36.21%). There were statistical differences in distribution of 1p/19 q LOH in different pathological types and pathological grades(P<0.05). Conclusions 1p/19 q LOH has a higher proportion in gliomas. Sex, age and side have nothing to do with 1p/19 q LOH. 1p/19 q LOH is associated with pathological type and pathological grade. Oligodendroglioma has the highest positive rate, followed by oligoastrocytoma, astrocytoma is the lowest one. With increasing of pathological grade, 1p/19 q LOH positive rate declined. 1p/19 q LOH may provide support to pathological diagnosis and tumor grade.Part Two: The Relationship Between 1p/19 q LOH, VEGF m RNA Expression And Prognosis in GliomasObjective To investigate the relationship between 1p/19 q LOH, VEGF m RNA expression and clinical prognosis in gliomas. Methods Realtime fluorescence quantitative PCR(RTFQ-PCR) was used to detect VEGF m RNA expression in 128 cases of newly diagnosed gliomas and 10 cases of brain tissues in Affiliated Hospital of Weifang Medical College and Affiliated Hospital of Qingdao University. Long-term follow-up was performed for all the patients. The potential relationship between 1p/19 q LOH, VEGF m RNA expression and pathological grade was analyzed by Chi-square test and t test, overall survival was evaluated by Kaplan-Meier method and log-rank test. Multivariate cox regression model was conducted to determine the independent prognostic factors for gliomas. P <0.05 was considered statistically significant. Results The relative quantity of VEGF m RNA expression in gliomas was significantly higher than in brain tissue(8.36±2.35 vs 1.41±0.53). The trend shows that the higher grade of glioma the more intense expression of VEGF m RNA(P<0.05). VEGF m RNA expression in non-1p/19 q LOH group was significantly higher than in 1p/19 q LOH group(P<0.05). Survival analysis showed that the survival time of patients with 1p/19 q LOH and VEGF m RNA low expression was significantly longer than that of patients with non-1p/19 q LOH and VEGF m RNA high expression, regardless of low grade gliomas and high grade gliomas. The Cox multivariate analysis showed that the WHO grade(HR=5.561, P<0.05) and VEGF m RNA expression levels(HR=3.649, P<0.05) were independent risk factors for gliomas. Although the 1p/19 q status was not associated with overall survival in the multivariate Cox regression model, a borderline significance was achieved(HR=2.158, P=0.058). Conclusions There is correlation among 1p/19 q LOH, VEGF m RNA expression, pathological grade and overall survival in gliomas. Combined detection can provide valuable assistance to pathological type, histological grade and prognosis in gliomas.