title: Prognostic significance of vascular invasion in intermediate-grade subtype of lung adenocarcinoma.
abstract: OBJECTIVE
  Although the recent reclassification of histological subtypes of lung adenocarcinoma reflects disease prognosis better, the prognosis of papillary and acinar-predominant adenocarcinoma, which are highly prevalent, is heterogeneity. The present study aimed to identify the prognostic indicators for papillary and acinar-predominant adenocarcinoma.
  
  
  METHODS
  This retrospective study included 315 consecutive patients with completely resected pathological N0 lung adenocarcinoma tumors ≤3 cm from two institutions. Tumors were classified according to histologically predominant subtypes as low-grade (adenocarcinoma in situ, minimally invasive adenocarcinoma or lepidic predominant), intermediate-grade (papillary or acinar predominant) or high-grade (solid or micropapillary predominant). Prognostic factors in intermediate-grade group were assessed among clinicopathological factors of age, gender, surgical procedure, tumor size, pleural, lymphatic and vascular invasion using Cox proportion hazards analyses.
  
  
  RESULTS
  There were 174 patients in the low-grade group, 109 in the intermediate-grade group and 32 in the high-grade group. The 3-year recurrence-free survival rates were 98.1%, 86.3% and 74.8% for these groups, respectively (P < 0.001). In the intermediate-grade group, the presence of vascular invasion was an independent prognostic factor on multivariate Cox regression analysis of recurrence-free survival (hazard ratio, 3.48; 95% confidence interval, 1.26-9.57, P = 0.01). Classification of intermediate-grade group based on vascular invasion revealed a clear division into favorable and unfavorable prognostic subgroups.
  
  
  CONCLUSIONS
  Consideration of the vascular invasion status in addition to the predominant subtype could provide a more accurate assessment of malignant aggressiveness and prognosis of patients with early-stage lung adenocarcinoma.
authors: Department of Surgical Oncology, Hiroshima University, Hiroshima.
authors: Norifumi
authors: N
authors: Tsubokawa
authors: Department of Surgical Oncology, Hiroshima University, Hiroshima.
authors: Takahiro
authors: T
authors: Mimae
authors: Department of Surgical Oncology, Hiroshima University, Hiroshima.
authors: Yoshihiro
authors: Y
authors: Miyata
authors: Department of Surgical Oncology, Hiroshima University, Hiroshima.
authors: Shinsuke
authors: S
authors: Sasada
authors: Department of Surgical Oncology, Hiroshima University, Hiroshima.
authors: Tomoharu
authors: T
authors: Yoshiya
authors: Department of Pathology, Hiroshima University, Hiroshima.
authors: Kei
authors: K
authors: Kushitani
authors: Department of Pathology, Hiroshima University, Hiroshima.
authors: Yukio
authors: Y
authors: Takeshima
authors: Department of Respiratory Medicine, Kanagawa Cancer Center, Yokohama.
authors: Shuji
authors: S
authors: Murakami
authors: Department of Pathology, Kanagawa Cancer Center, Yokohama.
authors: Tomoyuki
authors: T
authors: Yokose
authors: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
authors: Hiroyuki
authors: H
authors: Ito
authors: Department of Thoracic Surgery, Kanagawa Cancer Center, Yokohama, Japan.
authors: Haruhiko
authors: H
authors: Nakayama
authors: Department of Surgical Oncology, Hiroshima University, Hiroshima.
authors: Morihito
authors: M
authors: Okada
keywords: adenocarcinoma; predominant subtype; prognostic factor; vascular invasion