Richard S. Fraser

Canadian Anaplastic Lymphoma Kinase Study: A Model for Multicenter Standardization and Optimization of ALK Testing in Lung Cancer

Introduction: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals. Methods: Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study samples. Thirteen laboratories performed IHC using locally developed staining protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score. Twelve centers conducted FISH using protocols based on Vysis’ ALK break-apart FISH kit. Initial IHC results were used to optimize local IHC protocols, followed by a repeat IHC study to assess the results of standardization. Three laboratories conducted a prospective parallel IHC and FISH analysis on 411 consecutive clinical samples using post-validation optimized assays. Results: Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68, respectively. IHC optimization improved the intraclass correlation coefficients to 0.94. Factors affecting FISH scoring and outliers were identified. Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100% sensitivity and specificity for IHC versus FISH. Conclusions: Multicenter standardization study may accelerate the implementation of ALK testing protocols across a country/region. Our data support the use of an appropriately validated IHC assay to screen for ALK+ lung cancers.

Review of Thoracic Imaging Findings Unique to Women.

Purpose Traditionally, indications for imaging studies of women are considered to be related to screening for and evaluation of disease of the female breast and pelvis. However, a number of chest diseases and associated intrathoracic imaging findings are unique to women and should be recognized by general radiologists, as well as chest and women-imaging specialists. Conclusions The sex-specific findings unique to women include normal anatomical variants, primary lung disease, complications of breast and gynaecological disease, and pregnancy-related conditions. Classification, description, and illustration of gender-specific chest imaging findings are the objective of this article.