Analysis of major known driver mutations and prognosis in resected adenosquamous lung carcinomas.
BACKGROUND
Genotyping for driver mutations is now routinely used to guide clinical care of patients with lung cancer. Adenosquamous lung carcinoma (AdSqLC) is a subtype of cancer that contains both adenocarcinoma and squamous cell carcinoma. However, the incidence, clinicopathologic characteristics, and prognostic implications of major driver mutations in AdSqLCs are not well established.


METHODS
Seventy-six resected AdSqLCs and 646 lung adenocarcinomas were screened for known genetic alterations involving EGFR, ERBB2, KRAS, BRAF, PIK3CA, AKT1, RET, and ALK. Tumors showing acinar, lepidic, micropapillary, or papillary growth in glandular component were classified as classical AdSqLC.


RESULTS
Of the 76 AdSqLCs, 43 (56.6%) harbored known mutant kinases, including 24 (31.6%) with EGFR mutations, eight (10.5%) with KRAS mutations, two (2.6%) with AKT1 (2.6%) mutations, one (1.3%) with ERBB2 insertion mutation, one (1.3%) with PIK3CA mutation, four (5.3%) with ALK fusions, and three (4%) with KIF5B-RET fusions. No mutation was found in BRAF. The mutational profiles and clinicopathologic characteristics of classical AdSqLC were strikingly similar to that of poorly differentiated adenocarcinoma. However, AdSqLCs with solid growth pattern in glandular component had high frequency of ALK or RET fusions and low EGFR mutation rate.


CONCLUSIONS
To our knowledge, this is the first comprehensive study investigating major oncogenic driver mutations in a large cohort of AdSqLC patients in a Chinese population. The findings suggest that it will be clinically valuable to investigate the growth pattern of glandular component in AdSqLCs.
Departments of *Thoracic Surgery, ‖Pathology, †Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, China; ‡Department of Thoracic Surgery, Fudan University Hua Dong Hospital, Shanghai, China; §Promed Cancer Centers, Shanghai, China; ¶Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
Rui
R
Wang
Yunjian
Y
Pan
Chenguang
C
Li
Huibiao
H
Zhang
David
D
Garfield
Yuan
Y
Li
Ting
T
Ye
Haichuan
H
Hu
Xiaoyang
X
Luo
Hang
H
Li
Yang
Y
Zhang
Jie
J
Zhang
Xiaoyan
X
Zhou
Lei
L
Shen
William
W
Pao
Yihua
Y
Sun
Haiquan
H
Chen
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D018196:Carcinoma, Adenosquamous / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics
D000077548:Anaplastic Lymphoma Kinase; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D015514:Oncogene Proteins, Fusion; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D051096:Proto-Oncogene Proteins c-ret; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C573239:KIF5B-RET fusion protein, human; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C000626173:ALK protein, human; C508053:ERBB2 protein, human; C099282:RET protein, human; C494918:AKT1 protein, human; C482119:BRAF protein, human