Micropapillary Predominance Is a Risk Factor for Brain Metastasis in Resected Lung Adenocarcinoma

Takao Shigenobu, Yusuke Takahashi, Yohei Masugi, Ryutaro Hanawa, Hirokazu Matsushita, Atsushi Tajima, Hiroaki Kuroda

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Background: Histologic subtyping offers some prognostic value in lung adenocarcinoma. We thus hypothesized that histologic subtypes may be useful for risk stratification of brain metastasis (BM). In this study, we aimed to investigate the impact of histologic subtypes on the risk for BM in patients with resected lung adenocarcinoma. Patients and Methods: Of 1099 consecutive patients who had undergone curative-intent surgery (2000-2014), 448 patients who had undergone complete resection for lung adenocarcinoma were included in this study. Correlated clinical variables and BM-free survival were analyzed. Results: Micropapillary predominance was significantly associated with higher risk of BM after complete resection in univariate analyses (P < .001). In addition, multivariate analyses showed that micropapillary predominance was an independent risk factor for BM (hazard ratio = 2.727; 95% confidence interval, 1.260-5.900; P = .011), along with younger age and advanced pathologic stage. Unlike the other subtypes, an increase in the percentage of the micropapillary subtype was positively correlated with an increase in BM frequency. Patients with micropapillary adenocarcinoma showed significantly poorer brain metastasis-free survival compared with those with non-micropapillary adenocarcinoma (3 years, 78.2% vs. 95.6%; 5 years, 67.3% vs. 94.3%; P < .001). Conclusion: The current study demonstrated a significant correlation between micropapillary subtype and higher risk of BM in patients with resected lung adenocarcinoma. This routine histologic evaluation of resected adenocarcinoma may provide useful information for the clinician when considering postoperative management in patients with lung adenocarcinoma. Histologic subtyping offer some prognostic value in lung adenocarcinoma. Because brain metastasis is critical and often refractory to systemic chemotherapy, early detection is clinically important to achieve effective local treatment. We retrospectively analyzed the association between histologic subtypes and occurrence of brain metastasis and found a significant association between micropapillary predominance and higher risk for brain metastasis. Our findings may be relevant when considering postoperative management.

Original languageEnglish
Pages (from-to)e820-e828
JournalClinical Lung Cancer
Issue number6
Publication statusPublished - 2021 Nov


  • Aggressiveness
  • Distant metastasis
  • High-grade histology
  • Prognosis
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


Dive into the research topics of 'Micropapillary Predominance Is a Risk Factor for Brain Metastasis in Resected Lung Adenocarcinoma'. Together they form a unique fingerprint.

Cite this