Malignant pleural effusion cell blocks are substitutes for tissue in EML4-ALK rearrangement detection in patients with advanced non-small-cell lung cancer.

Abstract

OBJECTIVE:

To evaluate the feasibility of malignant pleural effusions (MPE) as surrogate samples for the detection of echinoderm microtubule-associated protein-like4 (EML4)-anaplastic lymphoma kinase (ALK) and to investigate the prognostic and predictive value of EML4-ALK in MPE of non-small-cell lung cancer (NSCLC).

METHODS:

One hundred and nine NSCLC patients were retrospectively analysed. EML4-ALK was identified using paraffin-embedded tumour cells in MPE samples by immunohistochemistry (IHC, Ventana) and confirmed by fluorescence using in situ hybridisation (FISH) and qRT-PCR. The EGFR mutation was determined by MPE, using denaturing high-performance liquid chromatography (DHPLC).

RESULTS:

A total of 5 out of 109 (4.58%) patients were identified as EML4-ALK rearrangement in MPE by IHC.; In addition to two metachronous samples, the consistency of MPE and tissue for EML4-ALK detection was 100% (21/21), and the sensitivity and specificity were 100% (2/2) and 100% (19/19), respectively. EML4-ALK rearrangement cases were confirmed by FISH and qRT-PCR; the sensitivity were both 100% (2/2) when compared with tissue, and it was 60% (3/5) and 100% (5/5), respectively, when compared with MPE by IHC. The overall response rate (ORR) was 100% (2/2) for patients with EML4-ALK in MPE. Moreover, the PFS of these patients appeared to be prolonged in chemotherapy (9.27 versus 6.53 and versus 4.67 months, P = 0.122), compared with the EGFR mutation and the EGFR/ALK double negative group, respectively.

CONCLUSION:

EML4-ALK rearrangement detection in malignant pleural effusions is a complementary method for EML4-ALK detection. VETANA and qRT-PCR are more appropriate for MPE detection. EML4-ALK rearrangement in pleural effusions has a predictive value for treatment.

• Authors: J Zhong, X Li, H Bai, J Zhao, Z Wang, J Duan, T An, M Wu, Y Wang, S Wang, J Wang
• Journal: Cytopathology : official journal of the British Society for Clinical Cytology (Cytopathology) Vol. 27 Issue 6 Pg. 433-443 (Dec 2016) ISSN: 1365-2303 [Electronic] England
• PMID: 27060609 (Publication Type: Journal Article)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• EML4-ALK fusion protein, human
• Oncogene Proteins, Fusion
• EGFR protein, human
• ErbB Receptors

Topics

• Adult
• Aged
• Carcinoma, Non-Small-Cell Lung (diagnosis, genetics, pathology)
• Cytodiagnosis
• ErbB Receptors (biosynthesis)
• Female
• Humans
• In Situ Hybridization, Fluorescence
• Male
• Middle Aged
• Oncogene Proteins, Fusion (genetics, isolation & purification)
• Pleural Effusion, Malignant (diagnosis, genetics, pathology)
• Prognosis