The more the micropapillary pattern in stage I lung adenocarcinoma, the worse the prognosis—a retrospective study on digitalized slides

Zombori, Tamás; Nyári, Tibor; Tiszlavicz, László; Pálföldi, Regina; Csada, Edit; Géczi, Tibor; Ottlakán, Aurél; Pécsy, Balázs; Furák, József

doi:10.1007/s00428-018-2337-x

Cited by 15 publications

(14 citation statements)

References 35 publications

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“…is further demonstrates that segmentectomy with maximal lung tissue retention is more suitable for patients with group A adenocarcinomas. Group B is more invasive than group A and, thus, is not suitable for segmentectomy [21]. is is consistent with the results of our research.…”

Section: Discussionsupporting

confidence: 92%

Analysis of Segmental Lymph Node Metastasis and Clinical Features in cT1N0M0 Lung Adenocarcinoma

Sun

Zou

et al. 2020

BioMed Research International

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The progression of lung adenocarcinoma through lymph node metastasis has been well established; however, the process of segmental lymph node (LSN) metastasis in cT1N0M0 lung adenocarcinoma remains unclear. We aimed to elucidate the markers of lymph node metastasis to different segments in early-stage lung adenocarcinoma and identify new indications for segmentectomy. A total of 200 patients were enrolled in this study. These patients were diagnosed with cT1N0M0 lung adenocarcinoma after positron emission tomography/computed tomography and received lobectomy and lymph node dissection surgeries. Lymph nodes retrieved from each station were sorted. The metastatic status of the isolated (i) LSNs and several characteristics were analyzed. Patients with ground-glass nodules (GGNs) (P=0.025), AIS/MIA/lepidic adenocarcinoma (P=0.038), nodules with a maximum diameter ≤1 cm (P=0.017), maximum standardized uptake value (SUVmax) < 2.5 (P=0.029), serum carcinoembryonic antigen (CEA) levels ≤4.5 ng/ml (P=0.036), and no N1 lymph nodes metastasis (P=0.036) had significantly lower iLSN metastasis rates than those without these characteristics. Pure GGNs, CEA levels ≤4.5 ng/ml, SUVmax < 2.5, tumors with a maximum diameter of ≤1 cm, or those confirmed to be adenocarcinoma in situ, minimally invasive adenocarcinoma, or invasive lepidic-predominant adenocarcinoma by frozen section may indicate segmentectomy. However, segmentectomy is not suitable for patients with metastasis to the N1 lymph nodes.

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Section: Discussionsupporting

confidence: 92%

Analysis of Segmental Lymph Node Metastasis and Clinical Features in cT1N0M0 Lung Adenocarcinoma

Sun

Zou

et al. 2020

BioMed Research International

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“…4 ) which was enriched in HLA-DR+ cells. Three of these samples were LPS tumors classified as stage IA or 0 cancers with small nodule size based on their CT scans (Table E4 ), and their histology is mostly lepidic which is associated with a favorable prognosis 27 . Conversely, the one LPS sample that deviated from this profile is a stage IB cancer, presents a bigger nodule size compared to the other LPS samples and has a predominant lepidic pattern but it also has a micropapillary component which is typically associated with a worse prognosis 27 .…”

Section: Discussionmentioning

confidence: 99%

“…Three of these samples were LPS tumors classified as stage IA or 0 cancers with small nodule size based on their CT scans (Table E4 ), and their histology is mostly lepidic which is associated with a favorable prognosis 27 . Conversely, the one LPS sample that deviated from this profile is a stage IB cancer, presents a bigger nodule size compared to the other LPS samples and has a predominant lepidic pattern but it also has a micropapillary component which is typically associated with a worse prognosis 27 . Finally, we validated our CyTOF findings by immunofluorescence and spatial analysis, in which we confirmed that the T cell abundance was positively correlated with HLA-DR expression in pan-cytokeratin+ cells and that T cells in LPS samples were closer to the first tumor cell in the space compared to SPS samples (Fig.…”

Section: Discussionmentioning

confidence: 99%

HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior

Senosain

Zou

Novitskaya

et al. 2021

Sci Rep

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Lung adenocarcinoma (ADC) is a heterogeneous group of tumors associated with different survival rates, even when detected at an early stage. Here, we aim to investigate whether CyTOF identifies cellular and molecular predictors of tumor behavior. We developed and validated a CyTOF panel of 34 antibodies in four ADC cell lines and PBMC. We tested our panel in a set of 10 ADCs, classified into long- (LPS) (n = 4) and short-predicted survival (SPS) (n = 6) based on radiomics features. We identified cellular subpopulations of epithelial cancer cells (ECC) and their microenvironment and validated our results by multiplex immunofluorescence (mIF) applied to a tissue microarray (TMA) of LPS and SPS ADCs. The antibody panel captured the phenotypical differences in ADC cell lines and PBMC. LPS ADCs had a higher proportion of immune cells. ECC clusters (ECCc) were identified and uncovered two ADC groups. ECCc with high HLA-DR expression were correlated with CD4+ and CD8+ T cells, with LPS samples being enriched for those clusters. We confirmed a positive correlation between HLA-DR expression on ECC and T cell number by mIF staining on TMA slides. Spatial analysis demonstrated shorter distances from T cells to the nearest ECC in LPS. Our results demonstrate a distinctive cellular profile of ECC and their microenvironment in ADC. We showed that HLA-DR expression in ECC is correlated with T cell infiltration, and that a set of ADCs with high abundance of HLA-DR+ ECCc and T cells is enriched in LPS samples. This suggests new insights into the role of antigen presenting tumor cells in tumorigenesis.

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“…In consistency with others' results [27][28][29][30][31], high architectural grade (solid and micropapillary tumors) was associated with an unfavorable outcome in our study. Furthermore, even a subdominant component of high-grade pattern is related to higher recurrence rate and tumor-related death [32].…”

Section: Discussionmentioning

confidence: 99%

Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas

Zombori

Sejben

Tiszlavicz

et al. 2020

Pathol. Oncol. Res.

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The spread through air spaces (STAS) has a main role in local recurrence of stage I lung adenocarcinomas (LAs), therefore its presence might question sublobar resection as a therapeutic option. The aim of our study was to evaluate the distribution of STAS in stage I LAs, to stratify patients according to local recurrence and to identify a group of patients who might be suitable for sublobar surgery. Patients resected with LA were included. The presence of STAS was recorded on hematoxylin eosin stained slides and clinicopathological data were obtained from medical charts. Overall survival (OS) and disease-free survival (DFS) were registered. Statistical methods included Kruskal-Wallis tests, Kaplan-Meier analyses, log-rank tests and Cox-regressions. 292 patients were included. STAS was identified in 38.7% and 95.7% of micropapillary carcinomas showed STAS. Significant correlation was found between STAS and high-grade patterns. Significant differences were found between OS and DFS estimates of STAS0 and STAS1 cases (5-y-OS: 80.0% vs. 68.4%; 5-y-DFS: 71.1% vs. 57.1%). The presence of STAS was associated with unfavorable prognosis in low and intermediate architectural grades, but not in high-grade. Multivariate analysis revealed that architectural grade (HR (OS) :2.09; HR (DFS) :1.52) and STAS (HR (OS) :1.51; HR (DFS) :1.48) were independent prognostic markers in stage I LA. Architectural grade combined with STAS was superior to other prognostic grades. The combination of architectural grade and STAS proved to be a prognostic factor that is superior to previously introduced grading systems. Patients having low and intermediate grade LAs without STAS might be eligible for sublobar resection.

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The more the micropapillary pattern in stage I lung adenocarcinoma, the worse the prognosis—a retrospective study on digitalized slides

Cited by 15 publications

References 35 publications

Analysis of Segmental Lymph Node Metastasis and Clinical Features in cT1N0M0 Lung Adenocarcinoma

Analysis of Segmental Lymph Node Metastasis and Clinical Features in cT1N0M0 Lung Adenocarcinoma

HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior

Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas

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