Abstract
BackgroundVentana ALK (D5F3) screening of anaplastic lymphoma kinase (ALK) gene rearrangement in tissue specimens has been approved by US FDA (Food and Drug Administration) to select treatment for non–small-cell lung carcinoma (NSCLC). However, tumor tissues are often not readily obtainable, and cytology specimens and may be the only tumor material available for diagnosis and molecular marker analysis. In this study, we evaluated the feasibility of ALK immunocytochemistry (ICC) on ThinPrep slides and determined a suitable scoring system for interpretation of the results.MethodsOne hundred twenty-one fine-needle aspirate (FNA) specimens from metastatic lesions of NSCLC were analyzed. ALK rearrangement was detected on ThinPrep cytology slides using the Ventana immunocytochemistry ALK-D5F3 system, which adopts two scoring systems for interpretation of the ICC results. The results were subsequently confirmed by reverse transcription polymerase chain reaction (RT-PCR) analysis and fluorescence in situ hybridization (FISH).ResultsAmong the 121 ICC specimens, 16 that were considered ALK-positive by either scoring system were referred for PCR analysis. Among the ALK ICC-negative cases, 33 had correlated FISH ALK results. A total of 49 specimens that exhibited either a positive or negative ICC result with a correlated ALK status were analyzed statistically. ICC results showed a high concordance rate with the results of PCR/FISH analysis. The sensitivity and specificity of ALK ICC by the binary scoring algorithm were 68.75 and 96.97%, respectively. These values increased to 93.75 and 96.97%, respectively, when interpreted by the semiquantified interpretation system.ConclusionsALK ICC analysis on ThinPrep slides is a reliable ALK testing method, and the semiquantified interpretation system on cytology specimens is recommended rather than the binary scoring algorithm on tissue specimens.
Highlights
Ventana ALK (D5F3) screening of anaplastic lymphoma kinase (ALK) gene rearrangement in tissue specimens has been approved by US FDA (Food and Drug Administration) to select treatment for non–small-cell lung carcinoma (NSCLC)
Specimens from the patients were selected for analysis on the following basis: (1) fine-needle aspirate (FNA) specimens were able to be obtained from metastatic lesions; (2) at least 15 mL of PreservCyt solution (Hologic Inc., Marlborough, MA, USA) was left in the specimen bottles; and (3) more than tumor cells were present in Papanicolaou-stained ThinPrep slides (Hologic Inc, Marlborough, MA, USA) [17]
Detection of ALK rearrangements Among the 121 specimens analyzed, 16 that were considered ALK-positive by ICC analysis were referred for PCR analysis, which confirmed an ALK-positive result in 15 cases
Summary
Ventana ALK (D5F3) screening of anaplastic lymphoma kinase (ALK) gene rearrangement in tissue specimens has been approved by US FDA (Food and Drug Administration) to select treatment for non–small-cell lung carcinoma (NSCLC). For the treatment of patients with NSCLC harboring anaplastic lymphoma kinase (ALK) gene fusions, crizotinib, ceritinib, and alectinib have all been approved. 3 methods of detecting ALK rearrangements are generally used: fluorescence in situ hybridization (FISH), reverse-transcription polymerase chain reaction (RT-PCR) assays, and immunohistochemistry (IHC) analysis. IHC is practicable and less costly, and has been approved by the US FDA as a screening assay for detecting ALK rearrangements [6,7,8,9]. Most studies of IHC have used tissue sections and only a few have focused on the feasibility of IHC using cytology specimens [10]
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