Tumor spread through air spaces (STAS) is a newly recognized pattern of invasion in lung adenocarcinoma. However, clinical significance of STAS has not yet been characterized in lung squamous cell carcinoma. In this study, we investigated whether STAS could determine clinical outcome in Japanese patients with lung squamous cell carcinoma. We reviewed tumor slides from surgically resected lung squamous cell carcinomas (n=216). STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. Tumors were evaluated for histologic subtypes, tumor budding, and nuclear diameter. Recurrence-free survival (RFS) was analyzed using the log-rank test and the Cox proportional hazards model. Tumor STAS was observed in 87 patients (40%), increasing incidence with lymph node metastasis (P=0.037), higher pathologic stage (P=0.026), and lymphatic invasion (P=0.033). All cases with STAS showed a solid nest pattern. The 5-year RFS for patients with STAS was significantly lower than it was for patients without STAS in all patients (P=0.001) and in stage I patients (n=134; P=0.041). On multivariate analysis, STAS was an independent prognostic factor of a worse RFS (hazard ratio=1.61; P=0.023). Patients with STAS had a significantly increased risk of developing locoregional and distant recurrences (P=0.012 and 0.001, respectively). We found that tumor STAS was an independent predictor of RFS in patients with resected lung squamous cell carcinoma, and it was associated with aggressive tumor behavior.

A growing number of independent studies have validated spread through air spaces (STAS) to be a predictor of worse prognosis in lung adenocarcinoma. To investigate the prognostic significance of STAS according to types of surgery and locations of recurrence, and the association between STAS and anti-anaplastic lymphoma kinase (ALK) expression, we analyzed a series of 735 Japanese patients with resected lung adenocarcinoma, which was restaged according to the 8th edition of TNM staging system. STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. Tumors were classified according to the 2015 WHO lung tumor classification. Recurrence-free probability and overall survival were analyzed using the log-rank test and the Cox proportional hazards model. STAS was observed in 247 patients. STAS was more frequently identified in ALK-positive tumors (P=0.020). STAS was an independent prognostic factor of a worse recurrence-free probability in all patients (hazard ratio [HR]=5.33, P<0.001) and in stage I patients (HR=6.87, P<0.001). STAS was an independent prognostic factor of a worse overall survival in all patients (HR=2.32, P<0.001) and in stage I patients (HR=2.85, P<0.001). In stage I patients with STAS, compared with lobectomy, limited resection was associated with a significantly higher risk of any recurrence (P=0.010) and locoregional recurrence (P=0.002). We have demonstrated that, in lung adenocarcinoma with STAS, limited resection was associated with a significantly higher risk of recurrence (especially locoregional recurrence) than lobectomy was.

Introduction: At present, cribriform arrangements are regarded as a pattern of acinar adenocarcinoma. However, recent studies have indicated that clinical outcomes for lung adenocarcinoma patients with cribriform subtype are unfavorable. To validate the prognostic significance of the cribriform pattern, we analyzed a series of 735 Japanese patients with resected lung adenocarcinoma, which was restaged according to the eighth edition of the TNM staging system.

Tomato wilt, caused by the soilborne fungus Fusarium oxysporum f. sp. lycopersici, is effectively controlled by a foliar spray of validamycin A (VMA) or validoxylamine A (VAA) (>/=10 mug/ml); however, neither VMA nor VAA is antifungal in vitro. In pot tests, the effect of a foliar application of VMA or VAA at 100 mug/ml lasted for 64 days. Plants sprayed with VMA or VAA accumulated salicylic acid and had elevated expression of the systemic acquired resistance (SAR) marker genes P4 (PR-1), Tag (PR-2), and NP24 (PR-5). Foliar spray of VMA also controlled late blight and powdery mildew of tomato. The disease control by VMA and VAA lasted up to 64 days after treatment, was broad spectrum, and induced the expression of PR genes, all essential indicators of SAR, suggesting that VMA and VAA are plant activators. The foliar application of plant activators is a novel control method for soilborne diseases and may provide an economically feasible alternative to soil fumigants such as methyl bromide.

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