Prognostic impact of vascular invasion and standardization of its evaluation in stage I non-small cell lung cancer

Diagn Pathol. 2015 Apr 2:10:17. doi: 10.1186/s13000-015-0249-5.

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.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5213064891369688.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Blood Vessels / chemistry
  • Blood Vessels / pathology*
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry / standards*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Lymphatic Vessels / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Pleura / pathology
  • Pneumonectomy
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Staining and Labeling / standards*
  • Time Factors
  • Treatment Outcome
  • Tumor Burden

Substances

  • Biomarkers, Tumor