Silva de Araujo Bruno Eduardo, Markgraf Mona, de Santana Almeida Araujo Isabela Karoline, Velleuer Eunike, Dietrich Ralf, Pomjanski Natalia, Schramm Martin
Department of Cytopathology, Heinrich Heine University, 40225 Düsseldorf, Germany.
Centre for Child and Adolescent Health, HELIOS Klinikum, 47805 Krefeld, Germany.
Cancers (Basel). 2022 Jul 17;14(14):3468. doi: 10.3390/cancers14143468.
Fanconi anemia (FA) is a rare inherited DNA instability disorder with a remarkably elevated risk of oral squamous cell carcinoma. These cancers can be detected with oral brush biopsy-based cytology even at early stages. This study aims to determine the diagnostic accuracy of a new multi-color fluorescent in situ hybridization (FISH) assay consisting of probes for , , and centromere of chromosome 6, as well as a 9p21 FISH assay consisting of probes for and centromere of chromosome 9 for the detection of oral (pre) malignant lesions in FA.
(I) Cutoffs for the dichotomization of positive or negative multi-color FISH results are determined and (II) retrospectively validated by using archived oral brush biopsy specimens from individuals with Fanconi anemia. In addition, the specimens for cutoff determination were re-hybridized with the 9p21 FISH assay.
A cutoff of six or more chromosomal aneuploid cells for a positive FISH result was determined in the cutoff study on 160 biopsy specimens. The validating of this cutoff on 152 specimens showed at best a sensitivity of 87% and a specificity of 82.9%.
Multi-color FISH is a sufficient tool to detect chromosomal aneuploidy in oral (pre) malignant lesions of individuals with Fanconi anemia. However, some false positive results may hamper the application as an adjuvant method to oral brush biopsy-based cytology in an oral cancer surveillance program.
范可尼贫血（FA）是一种罕见的遗传性DNA不稳定疾病，患口腔鳞状细胞癌的风险显著升高。即使在早期阶段，这些癌症也可以通过基于口腔刷检活检的细胞学检查检测出来。本研究旨在确定一种新的多色荧光原位杂交（FISH）检测方法的诊断准确性，该方法由针对染色体6的 、 、 和着丝粒的探针组成，以及一种由针对染色体9的 和着丝粒的探针组成的9p21 FISH检测方法，用于检测FA患者的口腔（癌前）恶性病变。
（I）确定多色FISH结果二分法的阳性或阴性临界值，（II）通过使用来自范可尼贫血患者的存档口腔刷检活检标本进行回顾性验证。此外，用于确定临界值的标本用9p21 FISH检测方法重新杂交。
在对160个活检标本进行的临界值研究中，确定FISH结果阳性的临界值为六个或更多染色体非整倍体细胞。在152个标本上对该临界值进行验证，结果显示敏感性最高为87%，特异性为82.9%。
多色FISH是检测范可尼贫血患者口腔（癌前）恶性病变中染色体非整倍体的一种有效工具。然而，一些假阳性结果可能会妨碍其作为口腔癌监测计划中基于口腔刷检活检的细胞学辅助方法的应用。
