Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid, Large Cell Neuroendocrine Carcinoma, and Small Cell Carcinoma of the Lung

Aly, Rania G.; Rekhtman, Natasha; Li, Xiaoyü; Takahashi, Yusuke; Eguchi, Takashi; Tan, Kay See; Rudin, Charles M.; Adusumilli, Prasad S.; Travis, William D.

doi:10.1016/j.jtho.2019.05.009

Cited by 69 publications

(65 citation statements)

References 35 publications

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“…Histological review showed that 26% of these patients had evidence of STAS, which was associated with distant metastasis, higher CIR and lung cancer-specific cumulative incidence of death overall (independently of histological subtype). 13 In fact, in patients with LCNEC and SCNEC, STAS was found to be an independent poor prognostic factor.…”

Section: Evolution Of the Concept Of Stas In Adenocarcinomamentioning

confidence: 95%

Updates on spread through air spaces (STAS) in lung cancer

Shih

Mino‐Kenudson

2020

Histopathology

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Air space invasion of tumours, particularly spread through air spaces (STAS), is a relatively recent concept that has been identified as a novel mechanism of invasion. It has predominantly been described in lung adenocarcinoma, although it may be seen in other primary lung malignancies as well. STAS in lung cancer has been reported to have numerous associations with poor survival. The objective of this article was to review the concept of air space invasion, update findings regarding its clinical impact, and discuss controversies in the field. With this aim, we performed a PubMed search of the English‐language literature. STAS has been introduced as a novel mechanism of invasion that is important for pathologists to recognise. There is a compelling body of evidence associating the presence of STAS with lower survival and suggesting that STAS is an independent prognostic factor, regardless of the stage of tumour. The standard of care for lung adenocarcinomas with STAS irrespective of size of tumour and nodal metastasis may be lobectomy rather than sublobar resection, owing to the risk of locoregional recurrence. Emerging data suggest that more work should be performed to improve consensus on and identification of STAS, including at frozen section.

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Section: Evolution Of the Concept Of Stas In Adenocarcinomamentioning

confidence: 95%

Updates on spread through air spaces (STAS) in lung cancer

Shih

Mino‐Kenudson

2020

Histopathology

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“…In another report, however, STAS was found to impact the cumulative incidence of recurrence (CIR) and to be an independent risk factor for lung cancerspecific cumulative incidence of death (LC-CID) in SCLC. 9 In large cell neuroendocrine carcinoma, the incidence of STAS was reported to be 43.0%, and STAS was also found to be an independent risk factor for CIR and LC-CID. In typical carcinoid, the incidence of STAS was from 16.0% to 20.5%, while in atypical carcinoid, this incidence was from 37.0% to 48.0%.…”

Section: Clinicopathologic Features and Prognosis Of Stasmentioning

confidence: 97%

“…1 STAS is defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. STAS was initially observed in adenocarcinomas (ADC) ( Figure 1A and B); however, with recent in-depth studies, STAS was identified in other types of lung cancer including squamous cell carcinoma (SQCC) ( Figure 1C and D), [2][3][4] pleomorphic carcinoma, 5 invasive mucinous adenocarcinoma (IMA) ( Figure 1E and F), 6,7 neuroendocrine tumors 8,9 and lymphoepithelioma-like carcinoma. 10 To date, several articles have reviewed the studies concerning the significance of STAS; [11][12][13] however, most of these articles focused on the correlation between STAS and clinicopathologic features or prognosis, and few articles summarized the significance of STAS on other aspects.…”

Section: Introductionmentioning

confidence: 93%

“…9,31 STAS was reported to be associated with CIR in atypical carcinoid; meanwhile, prognostic analysis in typical carcinoid was not conducted due to the small number of events. 9 In lymphoepithelioma-like carcinoma, the incidence of STAS was reported to be 25.0%, and there seemed to be no significant difference in prognosis between patients with and without STAS. 10…”

Section: Clinicopathologic Features and Prognosis Of Stasmentioning

confidence: 98%

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<p>Spread Through Air Spaces (STAS) in Lung Cancer: A Multiple-Perspective and Update Review</p>

Meng¹,

Yu²,

Gao³

et al. 2020

CMAR

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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.

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“…Regarding the definition of STAS, STAS is a novel pathologic feature in lung cancer that includes three histomorphological characteristics: solid nests, micropapillary patterns and single cells . STAS is also associated with recurrence and survival in squamous cell carcinoma, lung large cell neuroendocrine carcinoma, and lung small cell carcinoma, even lung pleomorphic carcinoma . STAS has been reported to be related with an aggressive tumor behavior, such as a larger tumor size, a high pathologic stage, lymphatic or vascular invasion, pleural invasion, tumor budding and increased micropapillary or solid structures in lung adenocarcinomas .…”

Section: Discussionmentioning

confidence: 99%

Relevance and prognostic ability of Twist, Slug and tumor spread through air spaces in lung adenocarcinoma

Liu

Sun

et al. 2020

Cancer Medicine

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Background Tumor spread through air spaces (STAS) is a novel pathologic characteristic in lung adenocarcinomas that indicates invasive tumor behavior. We aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial‐mesenchymal transition (EMT) and STAS. Materials and methods Our study retrospectively analyzed 115 patients with resected lung adenocarcinomas to evaluate the relationship between Twist, Slug and STAS. STAS was diagnosed using hematoxylin‐eosin (H&E) staining. Immunohistochemistry was used to evaluate the expression levels of Slug and Twist. Results In this study, 56 (48.7%) patients had STAS, 40 (34.8%) patients had Slug overexpression, and 28 (24.3%) patients had Twist overexpression. Patients with either STAS or Slug and Twist overexpression experienced poor recurrence‐free survival (RFS) and overall survival (OS). There were significant associations between Twist overexpression, Slug overexpression and the presence of STAS. The logistic model further revealed that pathological stage, Twist overexpression and Slug overexpression were independent risk factors for STAS. A multivariate analysis that contained Twist, Slug, pathologic stage and STAS, showed that pathologic stage and STAS were independent prognostic factors for poor RFS and OS. Another multivariate model that contained Twist, Slug and pathologic stage, showed that pathologic stage, Twist overexpression and Slug overexpression were independent risk factors for poor RFS and OS. In the cohort with STAS, the multivariate analysis showed that pathologic stage and Twist overexpression were independent risk factors for poor survival. The subgroup analysis showed that patients with both Slug overexpression and Twist overexpression with STAS received a poor prognosis. Conclusions STAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS.

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Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid, Large Cell Neuroendocrine Carcinoma, and Small Cell Carcinoma of the Lung

Cited by 69 publications

References 35 publications

Updates on spread through air spaces (STAS) in lung cancer

Updates on spread through air spaces (STAS) in lung cancer

<p>Spread Through Air Spaces (STAS) in Lung Cancer: A Multiple-Perspective and Update Review</p>

Relevance and prognostic ability of Twist, Slug and tumor spread through air spaces in lung adenocarcinoma

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