title: Prognostic impact of vascular invasion and standardization of its evaluation in stage I non-small cell lung cancer.
abstract: BACKGROUND
  Patients with pathologic stage (p-Stage) IA non-small cell lung cancer (NSCLC) have a good survival rate because of possible curative resection. However, up to 10% of these patients relapse postoperatively. To identify unfavorable prognostic factors, we retrospectively analyzed the clinicopathological features of p-Stage IA disease, focusing on vascular invasion.
  
  
  METHODS
  Of 467 patients with p-Stage I NSCLC, 335 were diagnosed with p-Stage IA or IB disease based on a lesion size ≤3 cm and the presence of pleural invasion (PL). Univariate and multivariate analyses of recurrence-free survival (RFS) were performed with age, sex, PL, and vascular invasion (blood vessel invasion [v] and lymphatic vessel invasion [ly]) as variables. To examine vascular invasion, hematoxylin-eosin (HE), Elastica van Gieson staining, and immunostaining with anti-podoplanin antibody were performed. The presence or absence of v and ly was recorded; the number of involved vessels was counted. Survival rates were obtained using the Kaplan-Meier method and log-rank test. Multivariate analyses were performed using the Cox proportional hazards model.
  
  
  RESULTS
  RFS differed significantly between patients with no or one involved blood vessel (0 v or 1 v) and those with ≥2 involved vessels (≥2 v). Similarly, RFS differed significantly between patients with no lymphatic vessel involvement (0 ly) and those with one involved lymphatic vessel (1 ly). Thus, BVI(+) and BVI(-) were defined as ≥2 v and 0 v + 1 v, and LVI(+) and LVI(-) as ≥1 ly and 0 ly, respectively. BVI and LVI together represented tumor vessel invasion (TVI). On multivariate analyses, PL and TVI were independently associated with recurrence. Additionally, patients with p-Stage IA TVI(+) disease had a comparable recurrence rate to those with p-Stage IB disease.
  
  
  CONCLUSIONS
  Similar to PL, TVI is an important factor increasing the likelihood of recurrence. As HE staining alone is insufficient for evaluating vascular invasion, specific staining is necessary. Moreover, patients with p-Stage IA TVI(+) disease had a recurrence rate comparable to those with p-Stage IB disease; therefore, further studies should aim to elucidate whether patients with p-Stage IA TVI(+) disease should be administered postoperative chemotherapy similar to that received by p-Stage IB patients.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5213064891369688.
authors.affiliation: Department of Thoracic Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan. rurika.hamanaka@gmail.com.|Division of General Thoracic Surgery, Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. rurika.hamanaka@gmail.com.
authors.forename: Rurika
authors.initials: R
authors.lastname: Hamanaka
authors.affiliation: Department of Pathology, Kanagawa Cancer Center Hospital, 2-3-2 Nakao, Asahi-Ku, Yokohama, Kanagawa, 241-8515, Japan. yokose-t@kcch.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.affiliation: Department of Pathology, Kanagawa Cancer Center Hospital, 2-3-2 Nakao, Asahi-Ku, Yokohama, Kanagawa, 241-8515, Japan. sakuma@sapmed.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakuma
authors.affiliation: Division of Thoracic Surgery, Respiratory Disease Center Yokohama City University Medical Center, 4-57 Urafune, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan. mtsuboi@east.ncc.go.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuboi
authors.affiliation: Department of Thoracic Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan. h-ito@kcch.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Thoracic Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan. nakayama-h@kcch.jp.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Thoracic Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan. yamadak@kcch.jp.
authors.forename: Kouzo
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. masudar@is.icc.u-tokai.ac.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Masuda
authors.affiliation: Division of General Thoracic Surgery, Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. Iwasaki@is.icc.u-tokai.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iwazaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010994:Pleura / Q000473:pathology; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D013194:Staining and Labeling / Q000592:standards*; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor