Original Articles
The Clinical Relevance of Pathologic Subtypes in Metastatic Lung Adenocarcinoma

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Introduction:

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.

Conclusion:

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.

Key words

Metastatic lung adenocarcinoma
Histopathology
EGFR
KRAS

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Disclosure: T.D.C. has received support to attend the World Conference on Lung Cancer 2013 from Boehringer Ingelheim. H.D. has received a Postdoctoral Cancer Research Fellowship from the Cancer Council of Victoria. V.S. reports her institution received funding to pay for statistical advice related to this manuscript and has provided consultancy services to the Victorian Department of Health. M.M.M. received a grant from the St. Vincent’s Hospital research endowment fund. G.M.W. reports his institution receives funding from Covidien for educational presentations, his institution has previously received a grant from Covidien, and he has previously received funding for meeting expenses from Karl Storz. Funding for this study was provided by St. Vincent’s Hospital research endowment fund. T.D.C. was supported by Australian Postgraduate Award from the University of Melbourne. G.M.W. was supported by National Health and Medical Research Council Scholarship GNT 1038699 and University of Melbourne Medical Postgraduate Committee Gordon-Taylor Scholarship. All other authors declare no conflict of interest.