Capouillez Aurélie, Debauve Gael, Decaestecker Christine, Filleul Olivier, Chevalier Dominique, Mortuaire Geoffrey, Coppée Frederic, Leroy Xavier, Belayew Alexandra, Saussez Sven
Laboratories of Anatomy, Faculty of Medicine and Pharmacy, University of Mons-Hainaut, Mons, Belgium.
Histopathology. 2009 Jul;55(1):77-90. doi: 10.1111/j.1365-2559.2009.03330.x.
To examine the immunohistochemical expression of helicase-like transcription factor (HLTF) in relation to the prognosis of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas, and to characterize the HLTF protein variants expressed in biopsy specimens of head and neck squamous cell carcinoma (HNSCC) as well as the HeLa cell line.
HLTF expression was determined by immunohistochemistry on a series of 100 hypopharyngeal (stage IV) and 56 laryngeal SCCs (stages I, II and IV). The HLTF variants were defined using reverse transcriptase-polymerase chain reaction and Western blots in 13 fresh HNSCC biopsies and in HeLa cells. High levels of HLTF expression were associated with rapid recurrence rates in a subgroup of 81 stage IV hypopharyngeal SCCs (with complete follow-up). A 95-kDa HLTF variant truncated at the carboxyl-terminal domain was detected in addition to the 115-kDa full-size protein in HNSCC biopsies, while six variants were observed in HeLa cells.
Our results demonstrate, for the first time, that hypopharyngeal SCCs presenting high levels of HLTF have a worse prognosis. The quantitative determination of HLTF in hypopharyngeal SCCs was an independent prognostic marker alongside tumour node metastasis staging. HNSCCs expressed the truncated HLTF variant lacking the domains involved in DNA repair.
研究解旋酶样转录因子(HLTF)的免疫组化表达与下咽鳞状细胞癌(HSCCs)和喉鳞状细胞癌(LSCCs)预后的关系,并鉴定在头颈部鳞状细胞癌(HNSCC)活检标本以及HeLa细胞系中表达的HLTF蛋白变体。
通过免疫组化对100例下咽癌(IV期)和56例喉鳞状细胞癌(I、II和IV期)进行HLTF表达检测。利用逆转录聚合酶链反应和蛋白质免疫印迹法对13例新鲜HNSCC活检标本和HeLa细胞中的HLTF变体进行鉴定。在81例IV期下咽鳞状细胞癌亚组(有完整随访)中,HLTF高表达与快速复发率相关。在HNSCC活检标本中,除了115 kDa的全长蛋白外,还检测到一种在羧基末端结构域截短的95 kDa的HLTF变体,而在HeLa细胞中观察到六种变体。
我们的结果首次表明,HLTF高表达的下咽鳞状细胞癌预后较差。下咽鳞状细胞癌中HLTF的定量测定是肿瘤淋巴结转移分期之外的一个独立预后标志物。HNSCC表达缺乏参与DNA修复结构域的截短型HLTF变体。