[375] EGFR and KRas Mutation Analysis in Lung Adenocarcinoma: Adequacy of Cytology Samples

Jonas J Heymann, Jad Saab, Joby Zachariah, Rana S Hoda. Weill Cornell Medical College, New York, NY

Background: Availability of targeted therapies for lung adenocarcinoma (ADCA) with epidermal growth factor receptor gene (EGFR) or Kirsten rat sarcoma virus oncogene homolog (KRas) mutation compels early testing for tumor mutations. Although cytologic specimens are increasingly being used for molecular testing (MT), adequacy of these samples for evaluation of EGFR and KRas mutation is controversial. In this study, cytologic sample adequacy for MT is assessed in a lung ADCA series.
Design: Lung ADCA cytology specimens on which MT was performed were identified retrospectively. All MT was performed on cell block (CB) sections prepared using either CytoLyt™ or CytoRich™ Red. Total number of tumor cells (“cellularity”) and percentage of nucleated cells that are tumor cells (“proportion”) for each CB were independently evaluated by 3 cytologists and compared to MT results. EGFR and KRas were evaluated by PCR-based methods by a reference laboratory with tumor microdissection where necessary.
Results: Nineteen lung ADCA cytology samples were identified. Of these, EGFR was evaluated on 18, KRas on 4, and both on 3. A majority contained more than 400 tumor cells (11/19, 58%) and greater than 50% tumor proportion (13/19, 68%). Only samples containing fewer than 400 tumor cells were insufficient (QNS) for MT, and a majority of such samples had less than 50% tumor proportion. Rate of mutation detection was compatible with that in the general population (Couraud. Eur J Cancer. 2012;48:1299). CBs from all EGFR positive (+) samples contained high tumor cellularity and proportion; one CB from a KRas (+) sample contained low tumor cellularity and proportion.

Molecular Testing Results by Tumor Cellularity and Proportion (# of cases)
 EGFRKRas
 +-QNS+-
Tumor Cells (#)<5000110
 50-40003401
 >40037002
Tumor Proportion (%)<5002410
 >5038103


For 3 cases, a negative EGFR MT result was concordant between cytology CB and corresponding tissue section. One tissue section corresponding to a QNS cytology sample was EGFR (+).
Conclusions: This study demonstrates that 13/18 (72%) lung ADCA cytology samples had sufficient material for EGFR testing, and all 4 were sufficient for KRas testing. All EGFR (+) cytology samples were highly cellular, suggesting the possibility of false negative MT in samples of low tumor cellularity and proportion. However, KRas mutation was successfully detected in a sample of low tumor cellularity and proportion.
Category: Cytopathology

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 68, Tuesday Afternoon

 

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