Abstract

Tumor spread through air space (STAS) is proposed as a new factor of lung cancer invasion, according to the new World Health Organization (WHO) classification. The aim of this study is to elucidate the prognostic impact and conduct a histopathological evaluation of STAS in primary lung cancer patients who underwent limited resection. We retrospectively collected 508 samples from p-Stage I primary lung cancer patients who underwent limited resection between 2004 and 2013. Hematoxylin and eosin stained tumor slides were reviewed to evaluate pathological features, including the presence or absence of STAS, and the morphological pattern in cases with STAS. We defined the pattern of STAS as single cell (SG), small cluster (SM), or large cluster (LG). Clinicopathological characteristics and patient outcome data were collected from medical records. SPSS statistical software (IBM Corporation, Somers, NY, USA) was used for statistical analysis. Histological diagnoses were 440 adenocarcinomas (Ad) (including 107 Adenocarcinoma in situ and 144 minimally invasive adenocarcinoma), 44 squamous cell carcinomas (Sq), and 24 other types of cancer. Seventy-six cases (15.0%: 60 Ad, 9 Sq, and 7 other types of cancer) were positive for STAS. The morphological STAS patterns were 12 SG, 45 SM, and 19 LG, respectively. There was no significant relationship between recurrence rate and morphological STAS pattern. The STAS-positive group was associated with the presence of micropapillary and/or solid components in Ad, and with lymphovascular and pleural invasion, compared to the STAS-negative group (p < 0.01). The median follow-up was 51 months. Eight local recurrences (1.6%), 16 locoregional (lung parenchyma, hilum, mediastinum) recurrences (3.1%), and 10 distant recurrences (2.0%) were recorded. In multivariate analysis, the risk of local (hazard ratio [HR]: 12.75; p < 0.01) and locoregional (HR: 4.12; p = 0.01) recurrence was significantly higher in the STAS-positive group than in the STAS-negative group. However, in a multivariate Cox model the presence of STAS was not associated with distant recurrence (p = 0.58). Our results indicated that the presence of STAS is a significant risk factor for local and locoregional recurrence, but not distant recurrence, in p-Stage I lung cancer following limited resection.

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