Morphometric and cytomorphologic characterization of EGFR-mutated cancer cells-comparison between cultured lung cancer cell lines and lung adenocarcinoma clinical samples.
BACKGROUND
Recently molecular targeting therapies such as inhibition of enzyme activities associated with gene mutations responsible for lung carcinogenesis have been demonstrating promising outcomes, increasing the importance of gene analysis using clinical samples. Cytomorphologic findings with predictive value toward specific gene mutation such as EGFR mutation could be a useful tool to select appropriate gene analyses using limited clinical samples.


METHODS
Morphometrical and cytomorphological evaluations were performed in 7 cultured lung cancer cell lines and 51 lung adenocarcinoma clinical samples to identify specific cytomorphologic characterization of EGFR-mutated cancer cells compared to the wild type.


RESULTS
Morphometry demonstrated that the EGFR mutated cell lines had significantly smaller nuclear area and perimeter and more circular nuclei compared to the wild type. In contrast, EGFR-mutated clinical samples had significantly greater nuclear area and perimeter compared to the wild type EGFR samples. There were no clear differences in cytomorphologic parameters assessing nuclear atypicality between EGFR mutated cells and wild type EGFR cells in either cultured cell lines or clinical samples.


CONCLUSIONS
Although our study suggested that EGFR mutation may have specific effects on nuclear morphology, no consistent characteristics of EGFR-mutated cells were identified in the clinical samples, probably due to various factors such as different pathologic stages and various incidences of lepidic growth. Further assessment of morphological characterization of EGFR-mutated cells in lung adenocarcinoma is warranted, increasing the number of samples and considering the effects of polyploidy, other gene mutations, pathology stage and tumor subtypes such as lepidic growth. Diagn. Cytopathol. 2016;44:717-724. © 2016 Wiley Periodicals, Inc.
Department of Pathology, Kumamoto University Hospital, Kumamoto, Japan.|Department of Pathology, Clinical Division National Kyusyu Cancer Center, Fukuoka, Japan.
Naoko
N
Nishiyama
Department of Pathology, Clinical Division National Kyusyu Cancer Center, Fukuoka, Japan.
Kenichi
K
Taguchi
Department of Pathology, Kurume University Medical Center, Kurume, Fukuoka, Japan.
Toshihiro
T
Yokoyama
Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.
Yukito
Y
Ichinose
Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka, Japan.
Masayoshi
M
Kage
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation
C512478:EGFR protein, human; D066246:ErbB Receptors
EGFR mutation; cytomorphology; cytomorphometry; lepidic growth; lung cancer