Bergshoeff Verona E, Van der Heijden Stijn J A, Haesevoets Annick, Litjens Sophie G H, Bot Fredrik J, Voogd Adri C, Chenault Michelene N, Hopman Anton H N, Schuuring Ed, Van der Wal Jacqueline M, Manni Johannes J, Ramaekers Frans C S, Kremer Bernd, Speel Ernst-Jan M
1Department of Otorhinolaryngology and Head and Neck Surgery, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Centre 2Department of Otorhinolaryngology and Head and Neck Surgery, Atrium Medical Centre, Heerlen 3Departments of Molecular Cell Biology 4Pathology 5Epidemiology 6School for Mental Health and Neuroscience 7Department of Methodology and Statistics, Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Centre 8Department of Pathology, University Medical Centre Groningen, The University of Groningen, The Netherlands.
Pathology. 2014 Apr;46(3):216-24. doi: 10.1097/PAT.0000000000000068.
The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7. Additionally, immunostainings for p53, Cyclin D1 and (p)FADD expression were evaluated. Malignant progression was recorded. Eighteen patients with carcinoma in situ (CIS) were treated after diagnosis and excluded from follow-up. Chromosome instability was strongly associated with a high risk of malignant transformation, especially in lower grade lesions (hyperplasia, mild and moderate dysplasia; odds ratio = 8.4, p = 0.004). Patients with lesions containing chromosome instability showed a significantly worse 5-year progression-free survival than those with premalignancies without chromosome instability (p = 0.002). Neither histopathology nor the protein markers predicted progression in univariate analysis, although histopathological diagnosis, p53 and FADD contributed positively to chromosome instability in multivariate analysis. Chromosome instability is associated with malignant progression of laryngeal premalignancies, especially in lower grade lesions. These results may contribute to better risk counselling, provided that they can be validated in a larger patient set.
喉癌前病变的组织病理学无法提供有关恶性转化风险的可靠信息，因此我们研究了可在临床实践中轻松应用的新分子标志物。对69例患者喉癌前病变的组织切片进行了1号和7号染色体着丝粒的双靶点荧光原位杂交（FISH）。1号和7号染色体的数目失衡和/或多体性表明存在染色体不稳定。此外，还评估了p53、细胞周期蛋白D1和（p）FADD表达的免疫染色。记录恶性进展情况。18例原位癌（CIS）患者在诊断后接受治疗并被排除在随访之外。染色体不稳定与恶性转化的高风险密切相关，尤其是在低级别病变（增生、轻度和中度发育异常；优势比=8.4，p=0.004）中。与无染色体不稳定的癌前病变患者相比，存在染色体不稳定病变的患者5年无进展生存率显著更差（p=0.002）。在单变量分析中，组织病理学和蛋白质标志物均未预测进展情况，尽管在多变量分析中，组织病理学诊断、p53和FADD对染色体不稳定有正向贡献。染色体不稳定与喉癌前病变的恶性进展相关，尤其是在低级别病变中。如果这些结果能够在更大的患者群体中得到验证，可能有助于更好地进行风险咨询。
