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Background: Although spread through air spaces (STAS) is a robust biomarker in surgically resected lung cancer, its application to biopsies is challenging. Moreover, limited resection is not an effective treatment for STAS-positive lung adenocarcinoma. This study aimed to identify histologic features from preoperative percutaneous transthoracic needle biopsies (PTNBs) to predict STAS status in the subsequently resected specimens, and thus help in selecting the surgical extent.Methods: Between January 2014 and December 2015, 111 PTNB specimens and subsequent resection specimens from consecutive lung adenocarcinoma patients were retrospectively examined. Histopathologic features of PTNB specimens and presence of STAS in subsequent resection specimens were evaluated and correlations between them were analyzed statistically.Results: The study participants had a mean age of 59 years (range, 35-81) and included 50 men and 61 women. Thirty-six patients were positive for STAS whereas 75 were negative. The micropapillary/solid histologic subtypes of lung adenocarcinoma (26 of 39; 66.7%; P <  0.001), necrotic/tumor debris (31 of 42; 73.8%; P <  0.001), intratumoral budding (ITB) (20 of 33; 60.6%; P <  0.001), desmoplasia (35 of 41; 85.4%; P <  0.001), and grade 3 nuclei (12 of 14; 85.7%; P <  0.001) were more common in STAS-positive tumors. Micropapillary/solid histologic subtype (OR, 1.35; 95% CI: 1.06, 1.67), ITB (OR, 1.64; 95% CI: 1.09, 2.83), desmoplasia (OR, 1.83; 95% CI: 1.36, 3.12), and N stage (N1 stage: OR, 1.37; 95% CI: 1.19, 1.87) (N2 stage: OR, 1.29; 95% CI: 1.07, 1.73) were independent predictors of STAS.Conclusions: Micropapillary/solid histologic subtype, ITB, and desmoplasia in preoperative PTNB specimens were independently associated with STAS in the subsequent resection specimens. Therefore, these can predict STAS and may help to optimize therapeutic planning. [ABSTRACT FROM AUTHOR]

Background: Spread through air spaces (STAS) is a spreading phenomenon of lung cancers, which is defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. To date, several articles have reviewed the studies concerning the significance of STAS; however, most articles focused on the prognosis without summarizing the significance of STAS on other aspects. In this review, we comprehensively summarized the current literature related to STAS, so as to explore the clinical significance of STAS from multiple perspectives. Main Body: This section provided a comprehensive overview of the significance of STAS from multiple perspectives and summarized current controversies and challenges in the diagnosis and clinical application. Conclusion: STAS is a conspicuous spreading phenomenon of lung cancers indicating worse prognosis; nevertheless, the treatment strategy for patients with STAS remains to be discussed. Further studies are needed to elaborate whether a STAS-positive patient who underwent limited resection needs a second operation or postoperative adjuvant treatment. Meanwhile, the internal mechanism of STAS formation is largely undiscovered. Whether the capability of detachment-migration-reattachment in STAS tumor cells is achieved at the time of primary tumorigenesis or in the progress of tumor development needs to be studied, and the related signal pathways or genetic alterations need to be explored. With this information, it may be possible to improve the prognosis of patients with STAS-positive lung cancers. [ABSTRACT FROM AUTHOR]

Objectives ROS1 rearrangement has been found in a subset of lung cancer and ROS1- rearranged tumors are sensitive to ALK kinase inhibitors. This study sought to evaluate the clinicopathological implications and histomorphological characteristics of ROS1 -rearranged tumors, especially micropapillary and aerogenous spread growth and to investigate the usefulness of ROS1 immunohistochemistry as a diagnostic test for ROS1 rearrangement. Materials and methods ROS1 rearrangement characterizations by fluorescence in situ hybridization and ROS1 protein and E-cadherin expression by immunohistochemistry were performed using 754 non-small cell lung cancer surgical specimens. Results ROS1 rearrangement was identified in 10 samples. Histologically, all 10 ROS1 -rearranged tumors harbored an adenocarcinoma component. Significantly, we noted a high association between ROS1 rearrangement with a micropapillary component ( p < 0.001), aerogenous spread ( p = 0.002), and E-cadherin loss ( p = 0.049). Survival analysis showed that ROS1 rearrangement was significantly associated with a higher risk of tumor recurrence ( p = 0.024). The best criterion to detect ROS1 -rearrangement by immunohistochemistry was an H-score of ≥100, with a sensitivity and specificity of 90% and 93.5%, respectively. Conclusions ROS1 -rearranged adenocarcinoma exhibited distinct morphological and clinicopathological features. Decreased membranous E-cadherin expression and aerogenous spread may be associated with worse disease-free survival. ROS1 immunohistochemistry correlated well with ROS1 gene rearrangement. [ABSTRACT FROM AUTHOR]

BACKGROUND Activating mutations in the epidermal growth factor receptor ( EGFR) in non-small cell lung carcinoma (NSCLC) are associated significantly with responsiveness to EGFR tyrosine kinase inhibitors. The objective of this study was to investigate the suitability of cytologic specimens for assessing EGFR mutations in lung adenocarcinomas. METHODS Sixty paired histologic and cytologic specimens of lung adenocarcinoma were collected. Exons 18 through 21 of the EGFR gene were amplified using polymerase chain reaction, and the mutation status of each sample was analyzed by pyrosequencing. A comparison of EGFR mutation status between histologic specimens and cytologic specimens was performed. RESULTS The overall EGFR mutation concordance rate between histologic specimens and corresponding cytologic specimens was 91.7%. No significant difference was observed in the concordance rate between cytologic specimens from primary lesions and specimens from metastatic lesions ( P = .63). The following parameters were correlated with the most reliable EGFR mutation results using the pyrosequencing method (100% concordance with the corresponding histologic specimens) in cytologic samples: a DNA concentration >25 ng/μL, content of >30 tumor cells, or a tumor percentage >30%. CONCLUSIONS In this study, routinely prepared cytologic specimens were reliable sources for assessing EGFR mutation status. The authors concluded that cytologic specimens from metastatic lesions and primary tumors are suitable for the successful assessment of EGFR mutation status. Cancer (Cancer Cytopathol) 2013;121:311-9. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Aims: The anaplastic lymphoma kinase gene ( ALK) has attracted considerable attention as a potential molecular target in non-small-cell lung cancer (NSCLC). However, it is unclear whether ALK alterations are acquired during the metastatic progression of NSCLC. Methods and results: ALK status and ALK expression were evaluated in a series of 67 primary NSCLCs and their corresponding metastatic lesions using fluorescence in-situ hybridization and immunohistochemistry. ALK rearrangement was detected in 7.5% (5/67) of the primary tumours and in 9.0% (6/67) of the metastases ( P < 0.001). ALK copy number gain (CNG) was detected in 1.5% (1/67) of the primary tumours and in 35.8% (24/67) of the metastases. Whereas ALK rearrangement was detected only in adenocarcinomas, CNG was identified in various histological subtypes of NSCLC. ALK expression was detected in 11.9% (8/67) of the primary tumours and in 25.4% (17/67) of the metastatic lesions. Conclusions: ALK alteration and ALK expression can be acquired during metastatic progression in NSCLC, and ALK CNG is associated with ALK expression. [ABSTRACT FROM AUTHOR]