Abstract
Tumor spread, in general, is the most important factor determining outcome in almost all malignant tumors. Lung tumors are unique with respect to potential routes for tumor dissemination, as apart from vascular, nodal, and distant spread of tumor cells, tumor spread through air spaces (STAS) might also occur. However, morphologic criteria for STAS and its prognostic impact have not been defined yet. We evaluated a series of 569 resected pulmonary adenocarcinomas (ADCs) for predefined morphologic criteria of limited and extensive STAS and correlated our findings with clinical, morphologic, molecular, and outcome data. Limited (21.6%) or extensive (29%) STAS was present in roughly half of all ADCs. The presence and type of STAS was tightly linked to specific growth patterns (P<0.001). STAS was much more prevalent in high-stage (P<0.001), nodal-positive (P<0.001) ADC with distant metastasis (P=0.010). STAS was associated with lower rates of EGFR (P=0.009) but higher rates of BRAF (P=0.016) mutations. Furthermore, STAS was associated with significantly reduced overall (P=0.020) and disease-free survival (P=0.004), which was growth pattern but not stage independent. We analyzed morphologic characteristics of a yet underestimated type of tumor spread of pulmonary ADC through air spaces. STAS is a novel morphologic prognosticator, which should be further validated and considered for implementation in routine diagnostic evaluation and reporting.
摘要
一般来说,肿瘤扩散是几乎所有恶性肿瘤最重要的预后决定因素。而肺肿瘤,肿瘤播散的潜在路径很独特,肿瘤细胞除了血管浸润、淋巴结转移和远处扩散外,还可发生沿气道扩散转移(STAS)。然而,STAS的形态学诊断标准和它对预后的影响仍不明确。
我们评估了569例肺腺癌(ADCs)切除标本,预先设定局限或广泛STAS的形态学标准,分析STAS与临床、病理形态学、分子及预后的相关性。
所有ADCs中大约有一半的病例发现局限性STAS(21.6%)或广泛性STAS(29%)。STAS的存在及其类型与特定的生长方式有紧密联系(P<0.001),stas更普遍见于adc中分期晚(p<0.001)、有淋巴结转移(p<0.001)、远处转移(p=0.010)的病例,stas与egfr突变率低(p=0.009)和braf突变率高(p=0.016)相关。而且,STAS与总体生存率显著降低(P=0.020)及无病生存率显著降低(P=0.004)相关。它是一种生长方式,而无分期意义。我们分析了肺ADC通过气道扩散(STAS)这种被低估的肿瘤扩散方式的形态学特征。
STAS是一个新的形态学预后因子,应该进一步验证,并在平常诊断和病理报告中实施运用。
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