The clinical relevance of pathologic subtypes in metastatic lung adenocarcinoma.
BACKGROUND
The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma recommends identification of pathologic patterns in metastatic samples where possible. We investigated the clinical relevance of these patterns.


METHODS
Patients with a surgical biopsy of lung adenocarcinoma from a metastatic site were included. Slides were reviewed by an anatomical pathologist identifying the histologic patterns of solid with mucin, acinar, micropapillary, papillary, and assigning a major adenocarcinoma subtype according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. EGFR and KRAS mutation testing were performed on formalin-fixed, paraffin-embedded blocks. Mutations were detected by high resolution melting assay with high resolution melting-positive samples confirmed by Sanger sequencing.


RESULTS
One-hundred patients were included. The major histologic subtype prevalence was as follows: solid (50), acinar (29), micropapillary (20), and papillary (1). Of 100 patients, 45 received no systemic therapy with no overall survival differences seen by histologic subtype and 55 received systemic therapy (chemoradiotherapy with curative intent or palliative chemotherapy). Worse survival was seen in the major solid histologic subtype compared with major acinar (hazard ratio 0.32 [95% confidence interval 0.15-0.68], p = 0.003) and micropapillary subtypes (hazard ratio 0.34 [95% confidence interval, 0.17-0.69], p = 0.003). The major solid histologic subtype was less likely to harbor EGFR mutations (p = 0.006) and was less frequent in never smokers (p = 0.010) compared with other histologic subtypes.


CONCLUSIONS
The major solid histologic subtype of lung adenocarcinoma at metastatic sites is associated with shorter overall survival on systemic anticancer therapy. Furthermore, the major solid histologic subtype is less likely to harbor EGFR mutations. These results require validation in larger cohorts.
*Department of Medical Oncology, St. Vincent's Hospital, Melbourne; †Department of Medicine, University of Melbourne; ‡Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Cancer Research, Olivia Newton John Cancer and Wellness Centre, Heidelberg; §Department of Pathology, University of Melbourne; ‖Department of Medicine, Eastern Hill Academic Centre, Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne; ¶Department of Respiratory Medicine, St. Vincent's Hospital; #Department of Thoracic Surgery, St. Vincent's Hospital, Melbourne; **Department of Surgery, University of Melbourne; and ††Department of Anatomical Pathology, St. Vincent's Hospital, Melbourne, Australia.
Timothy D
TD
Clay
Hongdo
H
Do
Vijaya
V
Sundararajan
Melissa M
MM
Moore
Matthew
M
Conron
Gavin M
GM
Wright
Sue-Anne
SA
McLachlan
Alexander
A
Dobrovic
Prudence A
PA
Russell
D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary* / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins