Parallel FISH and immunohistochemical studies of ALK status in 3244 non-small-cell lung cancers reveal major discordances.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangements occur in 1% to 7% of non-small-cell lung cancers (NSCLCs). Crizotinib, an ALK inhibitor, has been demonstrated to provide dramatic clinical benefits in ALK-positive advanced-stage NSCLC. Fluorescent in situ hybridization (FISH) has been established in clinical trials as the standard procedure method for detecting ALK rearrangements. Although the detection of ALK by immunohistochemistry (IHC) has been proposed for the screening of patients, large-scale studies are warranted to validate such a hierarchical approach. METHODS: In this article, we report the largest series thus far of parallel FISH and IHC ALK testing in 3244 consecutive NSCLC cases analyzed at two independent French centers. RESULTS: FISH-positive and/or IHC-positive results were demonstrated in 150 of 3244 cases (4.6%). An imbalanced sex ratio was detected, with women exhibiting a 2.2-fold relative risk for an alteration. Strikingly, only 80 of 150 specimens were classified as ALK positive by both techniques. The specimens with discordant FISH/IHC analyses were FISH-positive/IHC-negative (36), FISH-negative/IHC-positive (19), or FISH-noncontributive/IHC-positive (15). Thus, a single FISH or IHC analysis performed alone would have failed to detect approximately one-fourth of the ALK-positive cases with similar findings in our two centers. CONCLUSIONS: This study highlights the feasibility of systematic NSCLC testing by both FISH and IHC in routine practice. Many preanalytical factors may account for the apparent discrepancies between both methods, suggesting that hierarchical screening may underscore ALK-positive cases. This significant level of discrepancy supports the need of combined testing to optimize the detection of ALK-inhibitor-eligible patients given that some patients with discordant testing were found to respond to crizotinib.

[Pediatric lymphomas diagnosis after needle biopsy in Abidjan: value of cytology versus MYC translocation examination]. / Diagnostic des lymphomes pédiatriques après cytoponction à Abidjan : évaluation de la fiabilité de l'examen cytologique en comparaison avec l'étude du réarrangement de MYC.

OBJECTIVES: In Africa, lymphomas are widely represented by pediatric Burkitt lymphomas. In Abidjan, cytology performed after needle biopsy may be an examination of choice for pediatric lymphomas because of its low cost. We evaluated the value of this cytological examination in comparison with MYC rearrangement assessment. PATIENTS AND METHODS: A cytological examination was performed after needle biopsy of masses suspected for lymphoma. The reliability of this cytological examination was assessed versus a cytogenetic technique of fluorescence in situ hybridization with a probe targeting locus 8q24 (MYC) which is recurrently rearranged in Burkitt lymphomas. RESULTS: Thirty-four patients were enrolled in this study. The median age was 8 years old. The main locations of the suspicious masses were maxillofacial and abdominal. Thirty cytological examinations identified cytological aspects of Burkitt lymphoma. Among these cases, the cytogenetic technique identified 24 cytogenetic rearrangements compatible with a translocation involving MYC as described in Burkitt lymphoma. Six cytological examinations identified cytological aspects of Burkitt lymphoma without MYC translocation. Two cytological examinations were not compatible with Burkitt lymphoma and a normal MYC status was observed. Two cytological examinations were technically not contributive. CONCLUSIONS: The cytological examination showed good performance, notably with excellent sensitivity. The cytological examinations compatible with a Burkitt lymphoma without MYC translocation (6/30=20.0%) could be explained by the absence of translocation involving locus 8q24 (MYC) in some endemic Burkitt lymphomas.