Wolf Christina, Flechtenmacher Christa, Dietz Andreas, Weidauer Hagen, Abel Ulrich, Maier Heinz, Bosch Franz X
Molecular Biology Laboratory, Department of Otorhinolaryngology, University Hospital, School of Medicine, Heidelberg, Germany.
Laryngoscope. 2004 Apr;114(4):698-704. doi: 10.1097/00005537-200404000-00019.
OBJECTIVES/HYPOTHESIS: The progression of clinically manifest premalignant lesions in the head and neck region to primary or second primary cancer is characterized by numerical and structural chromosomal aberrations. However, many tumors arise from histologically inconspicuous mucosal sites. The objective was to investigate whether chromosomal aberrations can be detected in tumor-distant mucosa and whether they can help predict the risk of second primary malignancy.
A retrospective series of 72 clinically healthy, arbitrarily taken mucosal samples from 53 patients with squamous cell carcinoma of the head and neck was studied. A previous analysis of the p53 protein status had revealed both p53-positive and p53-negative samples.
The samples were analyzed by fluorescence in situ hybridization (FISH) using centromeric probes specific for the chromosomes 1, 10, 17, and 18.
Tumor-distant mucosa generally showed increased numerical chromosomal aberrations, which consisted mainly of monosomies. In the group of patients with p53-positive epithelia, all aberrations including gains of chromosomes (trisomies, tetrasomies) were more frequent. Monosomy for chromosome 17 was most significantly and selectively enhanced in this group (Wilcoxon Scores [rank sum] test, P =.0002).
Detectable chromosomal aberrations occur in clinically healthy epithelia in patients at risk for secondary head and neck cancer. Specifically, unbalanced chromosome 17 monosomy in conjunction with p53 protein overexpression may constitute a valuable biomarker for progressive "field cancerization."
目的/假设：头颈部临床上明显的癌前病变进展为原发性或第二原发性癌症的特征是染色体数目和结构异常。然而，许多肿瘤起源于组织学上不明显的黏膜部位。目的是研究是否能在远离肿瘤的黏膜中检测到染色体异常，以及它们是否有助于预测第二原发性恶性肿瘤的风险。
对53名头颈部鳞状细胞癌患者的72份临床健康、随机采集的黏膜样本进行回顾性研究。先前对p53蛋白状态的分析显示既有p53阳性样本也有p53阴性样本。
使用针对1、10、17和18号染色体的着丝粒探针，通过荧光原位杂交（FISH）对样本进行分析。
远离肿瘤的黏膜通常显示染色体数目异常增加，主要由单体组成。在p53阳性上皮患者组中，所有异常包括染色体增加（三体、四体）都更频繁。该组中17号染色体单体最为显著且有选择性地增加（Wilcoxon分数[秩和]检验，P = 0.0002）。
在有继发性头颈部癌风险的患者中，临床上健康的上皮中可检测到染色体异常。具体而言，17号染色体不平衡单体与p53蛋白过表达可能构成进行性“场癌化”的有价值生物标志物。
