Predictive EGFR gene analyses in cytology
2009
Bubendorf, L | Savic, S
EGFR mutations and EGFR gene copy number are considered as predictive markers for response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). NSCLC are often diagnosed by cytology alone. The isolation or selection of a pure tumour cell population is critical for mutation analysis by PCR and sequencing in order to avoid an admixture of tumour DNA with normal DNA of adjacent benign cells. The collection of tumour cells is easily possible by laser microdissection (LMD). EGFR FISH analysis on cytological specimens with a high proportion of benign respiratory cells should be performed after automated relocation of carcinoma cells. The only hitherto established EGFR-FISH criteria were developed using histological specimens and cannot be applied to cytological specimens as such. The cell nuclei in cytological specimens are intact, while they are often truncated in histological specimens. Therefore, when applying the Colorado criteria, the rate of FISH positive results is higher in cytological than in histological specimens and in fact represents false positive results in cytology. Cytological specimens are equally well suited for EGFR gene analyses and FISH analysis as histological specimens. At present, the value of EGFR-FISH analysis is limited by the lack of validated criteria for FISH positivity.
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