Bergshoeff Verona E, Balkenhol Maschenka C A, Haesevoets Annick, Ruland Andrea, Chenault Michelene N, Nelissen Rik C, Peutz Carine J, Clarijs Ruud, Van der Laak Jeroen A W M, Takes Robert P, Van den Brekel Michiel W, Van Velthuysen Marie-Louise F, Ramaekers Frans C S, Kremer Bernd, Speel Ernst-Jan M
Department of Otorhinolaryngology, Head and Neck Surgery, GROW-School for Oncology & Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
Department of Otorhinolaryngology and Head and Neck Surgery, Zuyderland Medical Center, 6419 PC Heerlen, The Netherlands.
Cancers (Basel). 2022 Jul 3;14(13):3260. doi: 10.3390/cancers14133260.
Background: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI. Methods: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/− 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%). Results: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%). Conclusions: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment.
为检测染色体不稳定性（CI），制定针对喉前体病变中FISH 1c/7c的客观、临床适用的评估标准。1号和7号染色体的拷贝数变异（CNV）反映了头颈部癌前病变的总体倍性状态，因此可用作CI的标志物。方法：我们对87例喉癌前病变的4μm福尔马林固定、石蜡包埋组织切片进行了1号和7号染色体着丝粒的双靶点FISH检测，以检测CNV。35例正常头颈部鳞状细胞样本用作对照。首先，评估每个病变的染色体7:1比率（CR）。CR的正常范围（≥0.84 ≤ 1.16）基于正常人群中发现的平均CR ± 3 x标准差。其次，确定含有超过2条1号和/或7号染色体的异常核百分比（PAN）（异常PAN的临界值≥10%）。结果：与CR相比，PAN与恶性进展的相关性更强（分别为OR 5.6，p = 0.001和OR 3.8，p = 0.009）。PAN与组织病理学相结合产生了一个预后模型，ROC曲线下面积（AUC）为0.75（标准误0.061，敏感性71%，特异性70%）。结论：与基于CR的标准相比，基于PAN≥10%的FISH 1c/7c评估标准为喉癌前病变恶性进展风险提供了最佳预后信息。FISH 1c/7c检测可与组织病理学评估联合应用。
