Epidermal growth factor receptor (EGFR) status and prognosis in Japanese patients can be predicted by a recently developed lung adenocarcinoma (ADC) classification system, say researchers.
The International Multidisciplinary Lung Adenocarcinoma Classification was published in 2011 following collaboration between the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society (IASLC/ATS/ERS).
Naoki Yanagawa and colleagues, from Yamagata Prefectural Central Hospital in Japan, tested the IASLC/ATS/ERS classification in 486 Japanese patients who underwent lung resection for ADC between 2002 and 2004 and were followed up regularly for an average of 40.5 months.
Using the 2004 World Health Organization guidelines, 84.6% of the patients were classified as having mixed ADC subtypes, the team writes in the Annals of Thoracic Surgery.
By contrast, according to the collaboration guidelines, 8.4% of tumours were classified as ADC in situ, 9.2% as minimally invasive ADC, 18.3% as lepidic predominant, 20.4% as acinar predominant and 28.0% as papillary predominant. A further 10.5% of tumours were solid predominant, 2.3% micropapillary predominant and 2.9% invasive mucinous ADC.
Overall, 131 of 241 tumours tested were positive for EGFR mutations, most commonly the missense L858R mutation in exon 21 (61.1%) or the in-frame deletion in exon 19 (36.6%).
And the frequency of EGFR mutation varied significantly between the different histopathological classifications, from 0% of invasive mucinous ADCs to 28% of solid predominant tumours, 43% of micropapillary predominant tumours, and 49% of acinar and 50% of papillary predominant tumours.
EGFR mutations were even more common in patients with minimally invasive ADC (60%), ADC in situ (62%) and lepidic predominant ADC (77%).
Survival analysis revealed three patterns of overall survival, so that patients with ADC in situ or minimally invasive ADC were considered to have low-grade tumours, patients with lepidic, papillary or acinar predominant disease or invasive mucinous ADC had intermediate-grade tumours, and patients with solid or micropapillary predominant disease had high-grade tumours.
In multivariate analysis, patients with high-grade tumours were 2.27 times more likely to die than patients with low- or intermediate-grade tumours after adjusting for age, gender, smoking status and other factors.
Age 68 years or older, stage II/III disease and lymphovascular invasion were also significant predictors of poor survival, observe Yanagawa et al.
“On the basis of these results, we believe that the new IASLC/ATS/ERS classification is a very useful predictive marker to plan and determine a therapeutic strategy for patients with lung ADC”, the team summarises.
The authors suggest that the correlation between EGFR status and tumour histopathology may be helpful in predicting whether a tumour will have a mutation and be likely to respond to EGFR-tyrosine kinase inhibitors.
Nevertheless, they conclude: “Further extensive studies will be needed to explore the association between these pathologic and molecular features.”
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