Molecular profiling of malignant pleural effusion in metastatic non-small-cell lung carcinoma the effect of preanalytical factors

Jamal H. Carter, James Adam Miller, David Feller-Kopman, David Ettinger, David Sidransky, Zahra Maleki

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Rationale: Non-small-cell lung cancer (NSCLC)-associated malignant pleural effusions (MPEs) are sometimes the only available specimens for molecular analysis. Objectives: This study evaluatesdiagnostic yield of NSCLC-associated MPE, its adequacy for molecular profiling and the potential influence of MPE volume/cellularity on the analytic sensitivity of our assays. Methods: Molecular results of 50 NSCLC-associated MPE cases during a 5-year period were evaluated. Molecular profiling was performed on cell blocks and consisted of fluorescent in situ hybridization (FISH) forALKgene rearrangements and the following sequencing platforms: Sanger sequencing (for EGFR) and highthroughput pyrosequencing (for KRAS and BRAF) during the first 4 years of the study period, and targeted next-generation sequencing performed thereafter. Results: A total of 50 NSCLC-associated MPE cases were identified wheremolecular testingwas requested. Of these, 17 cases were excluded: 14 cases (28%) due to inadequate tumor cellularity and 3 cases due to unavailability of the slides to review. A total of 27 out of 50MPE cases (54%) underwent at least EGFR and KRAS sequencing and FISH for ALK rearrangement. Of the 27 cases with molecular testing results available, a genetic abnormality was detected in 16 cases (59%). The most common genetic aberrations identified involved EGFR (9) and KRAS (7). Six cases had ALK FISH only, of which one showed rearrangement.MPE volume was not associated with overall cellularity or tumor cellularity (P=0.360). Conclusions: Molecular profiling of MPE is a viable alternative to testing solid tissue in NSCLC. This study shows successful detection of genetic aberrations in59%of sampleswithminimal risk of falsenegative.

Original languageEnglish (US)
Pages (from-to)1169-1176
Number of pages8
JournalAnnals of the American Thoracic Society
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

Fingerprint

Malignant Pleural Effusion
Non-Small Cell Lung Carcinoma
Fluorescence In Situ Hybridization
Neoplasms

Keywords

  • Lung adenocarcinoma
  • Malignant pleural effusion
  • Molecular profiling
  • Non-small-cell lung carcinoma
  • Preanalytical factors

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Molecular profiling of malignant pleural effusion in metastatic non-small-cell lung carcinoma the effect of preanalytical factors. / Carter, Jamal H.; Miller, James Adam; Feller-Kopman, David; Ettinger, David; Sidransky, David; Maleki, Zahra.

In: Annals of the American Thoracic Society, Vol. 14, No. 7, 01.07.2017, p. 1169-1176.

Research output: Contribution to journalArticle

Carter, Jamal H. ; Miller, James Adam ; Feller-Kopman, David ; Ettinger, David ; Sidransky, David ; Maleki, Zahra. / Molecular profiling of malignant pleural effusion in metastatic non-small-cell lung carcinoma the effect of preanalytical factors. In: Annals of the American Thoracic Society. 2017 ; Vol. 14, No. 7. pp. 1169-1176.
@article{f36d58c4fd894d0595d1e68ae006c37b,
title = "Molecular profiling of malignant pleural effusion in metastatic non-small-cell lung carcinoma the effect of preanalytical factors",
abstract = "Rationale: Non-small-cell lung cancer (NSCLC)-associated malignant pleural effusions (MPEs) are sometimes the only available specimens for molecular analysis. Objectives: This study evaluatesdiagnostic yield of NSCLC-associated MPE, its adequacy for molecular profiling and the potential influence of MPE volume/cellularity on the analytic sensitivity of our assays. Methods: Molecular results of 50 NSCLC-associated MPE cases during a 5-year period were evaluated. Molecular profiling was performed on cell blocks and consisted of fluorescent in situ hybridization (FISH) forALKgene rearrangements and the following sequencing platforms: Sanger sequencing (for EGFR) and highthroughput pyrosequencing (for KRAS and BRAF) during the first 4 years of the study period, and targeted next-generation sequencing performed thereafter. Results: A total of 50 NSCLC-associated MPE cases were identified wheremolecular testingwas requested. Of these, 17 cases were excluded: 14 cases (28{\%}) due to inadequate tumor cellularity and 3 cases due to unavailability of the slides to review. A total of 27 out of 50MPE cases (54{\%}) underwent at least EGFR and KRAS sequencing and FISH for ALK rearrangement. Of the 27 cases with molecular testing results available, a genetic abnormality was detected in 16 cases (59{\%}). The most common genetic aberrations identified involved EGFR (9) and KRAS (7). Six cases had ALK FISH only, of which one showed rearrangement.MPE volume was not associated with overall cellularity or tumor cellularity (P=0.360). Conclusions: Molecular profiling of MPE is a viable alternative to testing solid tissue in NSCLC. This study shows successful detection of genetic aberrations in59{\%}of sampleswithminimal risk of falsenegative.",
keywords = "Lung adenocarcinoma, Malignant pleural effusion, Molecular profiling, Non-small-cell lung carcinoma, Preanalytical factors",
author = "Carter, {Jamal H.} and Miller, {James Adam} and David Feller-Kopman and David Ettinger and David Sidransky and Zahra Maleki",
year = "2017",
month = "7",
day = "1",
doi = "10.1513/AnnalsATS.201609-709OC",
language = "English (US)",
volume = "14",
pages = "1169--1176",
journal = "Annals of the American Thoracic Society",
issn = "2325-6621",
publisher = "American Thoracic Society",
number = "7",

}

TY - JOUR

T1 - Molecular profiling of malignant pleural effusion in metastatic non-small-cell lung carcinoma the effect of preanalytical factors

AU - Carter, Jamal H.

AU - Miller, James Adam

AU - Feller-Kopman, David

AU - Ettinger, David

AU - Sidransky, David

AU - Maleki, Zahra

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Rationale: Non-small-cell lung cancer (NSCLC)-associated malignant pleural effusions (MPEs) are sometimes the only available specimens for molecular analysis. Objectives: This study evaluatesdiagnostic yield of NSCLC-associated MPE, its adequacy for molecular profiling and the potential influence of MPE volume/cellularity on the analytic sensitivity of our assays. Methods: Molecular results of 50 NSCLC-associated MPE cases during a 5-year period were evaluated. Molecular profiling was performed on cell blocks and consisted of fluorescent in situ hybridization (FISH) forALKgene rearrangements and the following sequencing platforms: Sanger sequencing (for EGFR) and highthroughput pyrosequencing (for KRAS and BRAF) during the first 4 years of the study period, and targeted next-generation sequencing performed thereafter. Results: A total of 50 NSCLC-associated MPE cases were identified wheremolecular testingwas requested. Of these, 17 cases were excluded: 14 cases (28%) due to inadequate tumor cellularity and 3 cases due to unavailability of the slides to review. A total of 27 out of 50MPE cases (54%) underwent at least EGFR and KRAS sequencing and FISH for ALK rearrangement. Of the 27 cases with molecular testing results available, a genetic abnormality was detected in 16 cases (59%). The most common genetic aberrations identified involved EGFR (9) and KRAS (7). Six cases had ALK FISH only, of which one showed rearrangement.MPE volume was not associated with overall cellularity or tumor cellularity (P=0.360). Conclusions: Molecular profiling of MPE is a viable alternative to testing solid tissue in NSCLC. This study shows successful detection of genetic aberrations in59%of sampleswithminimal risk of falsenegative.

AB - Rationale: Non-small-cell lung cancer (NSCLC)-associated malignant pleural effusions (MPEs) are sometimes the only available specimens for molecular analysis. Objectives: This study evaluatesdiagnostic yield of NSCLC-associated MPE, its adequacy for molecular profiling and the potential influence of MPE volume/cellularity on the analytic sensitivity of our assays. Methods: Molecular results of 50 NSCLC-associated MPE cases during a 5-year period were evaluated. Molecular profiling was performed on cell blocks and consisted of fluorescent in situ hybridization (FISH) forALKgene rearrangements and the following sequencing platforms: Sanger sequencing (for EGFR) and highthroughput pyrosequencing (for KRAS and BRAF) during the first 4 years of the study period, and targeted next-generation sequencing performed thereafter. Results: A total of 50 NSCLC-associated MPE cases were identified wheremolecular testingwas requested. Of these, 17 cases were excluded: 14 cases (28%) due to inadequate tumor cellularity and 3 cases due to unavailability of the slides to review. A total of 27 out of 50MPE cases (54%) underwent at least EGFR and KRAS sequencing and FISH for ALK rearrangement. Of the 27 cases with molecular testing results available, a genetic abnormality was detected in 16 cases (59%). The most common genetic aberrations identified involved EGFR (9) and KRAS (7). Six cases had ALK FISH only, of which one showed rearrangement.MPE volume was not associated with overall cellularity or tumor cellularity (P=0.360). Conclusions: Molecular profiling of MPE is a viable alternative to testing solid tissue in NSCLC. This study shows successful detection of genetic aberrations in59%of sampleswithminimal risk of falsenegative.

KW - Lung adenocarcinoma

KW - Malignant pleural effusion

KW - Molecular profiling

KW - Non-small-cell lung carcinoma

KW - Preanalytical factors

UR - http://www.scopus.com/inward/record.url?scp=85021785317&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021785317&partnerID=8YFLogxK

U2 - 10.1513/AnnalsATS.201609-709OC

DO - 10.1513/AnnalsATS.201609-709OC

M3 - Article

C2 - 28557526

AN - SCOPUS:85021785317

VL - 14

SP - 1169

EP - 1176

JO - Annals of the American Thoracic Society

JF - Annals of the American Thoracic Society

SN - 2325-6621

IS - 7

ER -