Bozzetti Cecilia, Nizzoli Rita, Tiseo Marcello, Squadrilli Anna, Lagrasta Costanza, Buti Sebastiano, Gasparro Donatello, Zanoni Daniele, Majori Maria, De Filippo Massimo, Mazzoni Francesca, Maddau Cristina, Naldi Nadia, Sammarelli Gabriella, Frati Caterina, Pinto Carmine, Ardizzoni Andrea
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Department of Biomedical, Biotechnological and Translational Sciences, University Hospital of Parma, Parma, Italy.
Diagn Cytopathol. 2015 Nov;43(11):941-6. doi: 10.1002/dc.23318. Epub 2015 Jul 7.
The identification of ALK and ROS1 rearrangements and the availability of an effective target therapy, such as crizotinib, represent a new option in the treatment of advanced non-small cell lung cancer (NSCLC) patients. In light of recent advances in non-invasive diagnostic procedures, we aimed to demonstrate that direct cytological smears are suitable for assessing ALK and ROS1 rearrangements in patients with NSCLC.
Fifty-five patients with a cytological diagnosis of lung adenocarcinoma (ADC) were evaluated for ALK rearrangements by fluorescence in situ hybridization (FISH) and 12 patients for ROS1 FISH rearrangements. Seventeen of the 55 cytological samples tested for ALK were obtained from the primary tumor and 38 from metastatic lesions. Ten of 12 samples evaluated for ROS1 were obtained from metastatic sites and two from the primary tumor.
ALK FISH was successful in 49/55 (89%) cytological ADC samples and ROS1 FISH in all 12 cytological samples. ALK rearrangements were found in 3/13 (23%) primary tumors and 7/36 (19%) metastatic sites. ROS1 rearrangements were found in one of the two primary tumors and in two of the 10 metastases. Two of the three rearranged cases were tested on cytology after knowing that they were rearranged on histology in order to increase representativeness of ROS1 rearranged cases in this study.
Whenever cytology represents the only available material for diagnosis and biological characterization of NSCLC, minimally invasive procedures may provide an additional important source of cellular material for FISH assessment of ALK and ROS1 rearrangements.
间变性淋巴瘤激酶（ALK）和ROS1重排的鉴定以及有效的靶向治疗药物（如克唑替尼）的出现，为晚期非小细胞肺癌（NSCLC）患者的治疗提供了新的选择。鉴于非侵入性诊断程序的最新进展，我们旨在证明直接细胞学涂片适用于评估NSCLC患者的ALK和ROS1重排。
通过荧光原位杂交（FISH）对55例经细胞学诊断为肺腺癌（ADC）的患者进行ALK重排评估，对12例患者进行ROS1 FISH重排评估。检测ALK的55份细胞学样本中，17份来自原发性肿瘤，38份来自转移灶。评估ROS1的12份样本中，10份来自转移部位，2份来自原发性肿瘤。
49/55（89%）的细胞学ADC样本ALK FISH检测成功，所有12份细胞学样本ROS1 FISH检测均成功。在13份原发性肿瘤中有3份（23%）发现ALK重排，在36份转移灶中有7份（19%）发现ALK重排。在2份原发性肿瘤中的1份以及10份转移灶中的2份发现ROS1重排。在已知3例重排病例的组织学重排情况后，对其中2例进行了细胞学检测，以增加本研究中ROS1重排病例的代表性。
当细胞学是NSCLC诊断和生物学特征分析的唯一可用材料时，微创程序可能为ALK和ROS1重排的FISH评估提供额外重要的细胞材料来源。
