Reduced Fhit expression in cervical carcinoma: correlation with tumor progression and poor prognosis
Reduced Fhit expression in cervical carcinoma: correlation with tumor progression and poor prognosis
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DOI：
10.1016/s0090-8258(03)00318-4
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发表时间：
2003-08-01
影响因子：
4.7
通讯作者：
Chen, TJ
中科院分区：
文献类型：
--
作者：
Huang, LW;Chao, SL;Chen, TJ
Objective.脆性组氨酸三联体（FHIT）基因位于染色体3p14.2，包括共同的脆性位点FRA3B，这可能有助于染色体断裂和癌细胞重排。FHIT基因的异常蛋白表达和失活已经在多种癌前病变和癌性病变中被鉴定。为了确定FHIT基因在宫颈癌发展中的潜在意义，并探讨基因表达变化的临床意义，我们评估了宫颈癌前病变和宫颈癌中Fhit蛋白的水平。在我们的研究中，15例低度鳞状上皮内病变（LSIL），35例高度鳞状上皮内病变（HSIL），12例微浸润癌和103例浸润癌进行了评估。免疫组化法检测Fhit蛋白的表达。正常上皮和LSIL的所有样品均表现出中等至强的Fhit免疫染色。103例浸润性癌中30例（29.1%）、12例微浸润性癌中1例（8.3%）和35例HISL中3例（8.6%）Fhit蛋白表达降低。与正常上皮和不典型增生相比，微浸润癌和浸润癌的Fhit表达显著降低。Fhit表达与临床病理状态相关。Fhit表达降低与淋巴结转移显著相关（P = 0.005）。子宫旁浸润（P = 0.023）和阴道受累（P = 0.016）。在单因素分析中，Fhit表达是一个显著的生存预测因子（相对危险度2.54，P = 0.0091）：Fbit表达降低的患者死于宫颈癌的风险比表达相反的患者高154%。我们的研究结果表明，Fhit表达的免疫染色有可能作为宫颈癌管理的预后标志物。在微侵袭性和侵袭性癌中Fhit表达降低的趋势表明Fbit的下调与癌症进展密切相关。此外，Fhit表达的缺失与宫颈癌的淋巴结转移、宫旁浸润和阴道受累有关。这些结果表明，Fhit蛋白的丢失与宫颈癌的高侵袭性表型相关。(C)2003年爱思唯尔公司All rights reserved.
Objective. The fragile histidine triad (FHIT) gene is located at chromosome 3p14.2 and encompasses the common fragile site, FRA3B, which may contribute to chromosome breakage and rearrangement of cancer cells. Aberrant protein expression and inactivation of the FHIT gene have been identified in a variety of precancerous and cancerous lesions. To identify the potential implications of the FHIT gene in the development of cervical carcinoma and explore the clinical importance of change in gene expression, we assessed the level of Fhit protein in precancerous lesions and carcinomas of the cervix.Methods. In our study, 15 low-grade squamous intraepithelial lesions (LSIL), 35 high-grade squamous intraepithelial lesions (HSIL), 12 microinvasive carcinomas, and 103 invasive carcinomas were evaluated. The expression of Fhit was studied by immunohistochemistry using a polyclonal antibody specific for the protein.Results. All samples of normal epithelium and LSIL exhibited intermediate to strong immunostaining of Fhit. Reduced Fhit protein expression was observed in 30 of 103 (29.1%) invasive carcinomas, I of 12 (8.3%) microinvasive carcinomas, and 3 of 35 (8.6%) HISL. Compared with normal epithelium and dysplasia, microinvasive and invasive carcinomas showed significantly lower Fhit expression. Fhit expression was also correlated with clinicopathological status. Reduced Fhit expression was significantly associated with lymph node metastasis (P = 0.005). parametrial invasion (P = 0.023), and vaginal involvement of the tumor (P = 0.016). In univariate analysis, Fhit expression was found to be a significant predictor of survival (relative risk 2.54, P = 0.0091): the patient with reduced Fbit expression had a 154% higher risk of dying from cervical cancer than the patient with opposite values.Conclusions. Our results indicate that immunostaining of Fhit expression has potential as a prognostic marker in the management of cervical cancer. The trend of reduced Fhit expression in microinvasive and invasive carcinomas suggests that down-regulation of Fbit is strongly linked to cancer progression. Moreover, loss of Fhit expression was related to lymph node metastasis, parametrial invasion, and vaginal involvement in cervical carcinoma. These results imply that loss of Fhit protein is associated with highly aggressive phenotypes of cervical carcinoma. (C) 2003 Elsevier Inc. All rights reserved.