Ariel I, Sughayer M, Fellig Y, Pizov G, Ayesh S, Podeh D, Libdeh B A, Levy C, Birman T, Tykocinski M L, de Groot N, Hochberg A
Department of Pathology and the Quantitative Molecular Pathology Unit, Hadassah Medical Centre and the Hebrew University-Hadassah Medical School, PO Box 24035, il-91240, Israel.
Mol Pathol. 2000 Dec;53(6):320-3. doi: 10.1136/mp.53.6.320.
To investigate the expression of the imprinted oncofetal H19 gene in human bladder carcinoma and to examine the possibility of using it as a tumour marker, similar to other oncofetal gene products.
In situ hybridisation for H19 RNA was performed on 61 first biopsies of bladder carcinoma from Hadassah Medical Centre in Jerusalem. The intensity of the reaction and the number of tumour cells expressing H19 in each biopsy were evaluated in 56 patients, excluding biopsies with carcinoma in situ. The medical files were searched for demographic data and disease free survival.
More than 5% of cells expressed H19 in 47 of the 56 (84%) biopsies. There was a decrease in the number of cells expressing H19 with increasing tumour grade (loss of differentiation) (p = 0.03). Disease free survival from the first biopsy to first recurrence was significantly shorter in patients with tumours having a larger fraction of H19 expressing cells, controlling for tumour grade. This was also supported by the selective analysis of tumour recurrence in patients with grade I tumours.
It might be possible to use H19 as a prognostic tumour marker for the early recurrence of bladder cancer. In addition, for the gene therapy of bladder carcinoma that is based on the transcriptional regulatory sequences of H19, the expression of H19 in an individual biopsy could be considered a predictive tumour marker for selecting those patients who would benefit from this form of treatment.
研究印记癌胚基因H19在人膀胱癌中的表达情况,并探讨将其作为肿瘤标志物的可能性,类似于其他癌胚基因产物。
对耶路撒冷哈达萨医疗中心的61例原发性膀胱癌活检组织进行H19 RNA的原位杂交。在56例患者中评估每次活检中H19反应的强度和表达H19的肿瘤细胞数量,不包括原位癌活检。查阅病历以获取人口统计学数据和无病生存期。
56例活检中有47例(84%)超过5%的细胞表达H19。随着肿瘤分级增加(分化丧失),表达H19的细胞数量减少(p = 0.03)。在控制肿瘤分级的情况下,H19表达细胞比例较大的肿瘤患者从首次活检到首次复发的无病生存期明显较短。I级肿瘤患者肿瘤复发的选择性分析也支持了这一点。
H19有可能作为膀胱癌早期复发的预后肿瘤标志物。此外,对于基于H19转录调控序列的膀胱癌基因治疗,个体活检中H19的表达可被视为选择那些将从这种治疗形式中受益的患者的预测性肿瘤标志物。