Driver mutations found in more than half of adenosquamous lung carcinomas

By Joanna Lyford, Senior medwireNews Reporter

Analysis of a large cohort of Chinese patients with adenosquamous lung carcinoma (AdSqLC) has identified known mutant kinases in more than half of the tumours, researchers report in the Journal of Thoracic Oncology.

Genotyping identified mutations in the EGFR, KRAS, AKT1, ERBB2, and KIF5B-RET genes but none in BRAF.

Interestingly, mutational profiles and clinicopathological characteristics of AdSqLC – a subtype of cancer that encompasses both adenocarcinoma and squamous cell carcinoma – were “strikingly similar” to those of poorly differentiated adenocarcinoma, yet overall survival was worse in AdSqLC, report Haiquan Chen (Fudan University Shanghai Cancer Center, China) and fellow authors.

The team studied 76 patients with resected AdSqLC and 646 with lung adenocarcinoma. Known genetic alterations were identified in 56.6% of AdSqLC samples and 80.7% of adenocarcinomas.

In both groups, EGFR mutations were the most common, with a frequency of 31.6% among the AdSqLC cases and 61.6% in adenocarcinomas, followed by KRAS mutations, with frequencies of 10.5% and 7.4%, respectively.

Other driver mutations included PIK3CA mutation, ALK fusion, AKT1 mutation, ERBB2 insertion mutation, and KIF5B-RET fusion.

Mutation profiles were very similar between AdSqLC and poorly differentiated lung adenocarcinoma, state Chen and co-authors, with similar frequencies of EGFR and KRAS mutations.

The exception was the subtype of AdSqLC with a solid growth pattern, which accounted for 30.3% of cases. In these tumours, the frequency of fusion genes (RET and ALK) was much higher than in AdSqLCs with a classical glandular component, at 30.4% versus 0%. Conversely, EGFR mutations were significantly less frequent, at 4.3% versus 43.4%.

Finally, clinical outcomes for people with AdSqLC did not differ between those with EGFR mutations versus KRAS-mutant, ALK-mutant or wild-type tumours, but were worse for people with KRAS mutations than those with ALK rearrangements.

Also, people with AdSqLC had comparable recurrence-free survival but worse overall survival than people with moderately-to-well-differentiated adenocarcinomas.

This indicates that “relapsed classical AdSqLCs may have more aggressive behavior and respond poorly to current therapies” say the authors, adding: “[S]tudies with a much larger sample size and longer duration of follow-up are still necessary to confirm these results.”

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