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Objectives: We evaluated the clinicopathological and oncological characteristics of epidermal growth factor receptor-mutated clinical stage IA radiological pure-solid lung adenocarcinoma and compared them with those of a ground-glass opacity component., Methods: Between 2008 and 2020, data from 1014 surgically resected clinical stage 0-IA epidermal growth factor receptor-mutated lung adenocarcinomas were evaluated. Oncological outcomes were assessed using multivariable analysis. Overall survival was estimated using Kaplan-Meier analysis and the log-rank test. The cumulative incidence of recurrence was estimated using the Gray's test., Results: Of these, 233 (23%) were radiologically pure-solid tumors, which demonstrated a higher proportion of nodal metastasis, micropapillary component, spread through alveolar space, and Ex19 subtype compared with those of tumors with ground-glass opacity (P < .001). Multivariable analysis revealed that the presence of ground-glass opacity was an independently significant factor for overall survival (P = .037) and cumulative incidence of recurrence (P < .001). In cases where the oncological outcomes were stratified by the presence of ground-glass opacity component, the 5-year overall survival was excellent at more than 90% in tumors with ground-glass opacity despite clinical-T categories (P = .2044); however, tumor size significantly affected survival only in pure-solid tumors (T1a, 100%; T1b, 77.7%; T1c, 68.5%; P = .0056). Furthermore, the cumulative incidence of recurrence was low in tumors with ground-glass opacity despite the clinical-T categories, whereas tumor size significantly affected the cumulative incidence of recurrence only in pure-solid tumors (5-year cumulative incidence of recurrence: T1a-b, 18.9%; T1c, 41.3%; P < .001)., Conclusions: Oncologic behavior and prognosis of radiologically pure-solid tumors were significantly poorer than those of tumors with ground-glass opacity among patients with epidermal growth factor receptor-mutated early-stage lung adenocarcinoma. These findings imply distinct tumorigenesis based on the presence of ground-glass opacity, even in tumors with epidermal growth factor receptor mutations., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Based on the current World Health Organization classification criteria, five of 3895 consecutive cases of surgically resected primary lung carcinomas (0.13%) categorized as enteric-type were analyzed. Three cases completely comprised tumor cells that resemble colorectal adenocarcinoma, while the other two cases exhibited features of conventional adenocarcinomas admixed with enteric components. Immunohistochemically, all patients expressed at least three of the five intestinal markers: CDX2, CK20, HNF4α, MUC2, and SATB2. None of the patients expressed TTF-1 and NKX3.1. Three cases showed nuclear accumulation of β-catenin, indicating activation of the Wnt/β-catenin signaling pathway; APC mutations were detected in one of these cases. TP53 mutations were detected in three cases. Mutated EGFR or ALK fusions were not detected. Our study demonstrates that pulmonary enteric-type adenocarcinomas share immunohistochemical features and genetic alterations with colorectal adenocarcinomas, which are characterized by frequent activation of the Wnt/β-catenin signaling pathway and a lack of actionable mutations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Invasive mucinous lung adenocarcinoma (IMA) has unique radiological findings and pathological characteristics. IMA is classified into solitary and pneumonic types; however, it is unclear whether these are biologically identical., Methods: A single-center retrospective analysis was performed for 70 IMA patients (solitary type [n = 38] and pneumonic type [n = 32]) who underwent pulmonary resection between January 2010 and December 2018. We compared clinical and biological characteristics between the two types., Results: The frequencies of genetic alternations such as EGFR, KRAS, BRAF, GNAS, ERBB2, TP53, NRG1, and MET were not different. Immunohistochemically, expression of MUC1 was significantly more common in the pneumonic type (5.0% versus 20.0%, p = 0.01) and diffuse MUC6 positive in the solitary type (39.0% versus 13.0%, p = 0.02). We further classified solitary types into those with or without ground-glass opacity (GGO) and pneumonic types into those with or without crazy-paving appearance (CPA), and evaluated their surgical outcomes. Five-year overall survival and relapse free survival rates were 95.8%/86.6%, 64.3%/70.7%, 74.6%/68.9%, and 50.0%/28.6% in patients with solitary type with GGO, solitary type without GGO, pneumonic type without CPA, and pneumonic type with CPA, respectively., Conclusions: There were no differences in genetic alternations; however, mucin expression pattern was different. Surgical outcomes were different according to the presence of GGO in the solitary type and the presence of CPA in the pneumonic type. These findings suggested a stepwise progression from solitary to pneumonic IMA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: A distinct subset of lung adenocarcinomas (LADs), arising from a series of peripheral lung cells defined as the terminal respiratory unit (TRU), is characterised by thyroid transcription factor 1 (TTF-1) expression. The clinical relevance of transcription factors (TFs) other than TTF-1 remains unknown in LAD and was explored in the present study., Methods and Results: Seventy-one LAD samples were subjected to high-throughput transcriptome screening of LAD using cap analysis gene expression (CAGE) sequencing data; CAGE provides genome-wide expression levels of the transcription start sites (TSSs). In total, 1083 invasive LAD samples were subjected to immunohistochemical examination for paired box 9 (PAX9) and TTF-1 expression levels. PAX9 is an endoderm development-associated TF that most strongly and inversely correlates with the expression of TTF-1 TSS subsets. Immunohistochemically, PAX9 expression was restricted to the nuclei of ciliated epithelial and basal cells in the bronchi and bronchioles and the nuclei of epithelial cells of the bronchial glands; moreover, PAX9 expression was observed in 304 LADs (28%). PAX9-positive LADs were significantly associated with heavy smoking, non-lepidic subtype, EGFR wild-type tumours and PD-L1 expression (all P < 0.0001). All these characteristics were opposite to those of TRU-type LADs with TTF-1 expression. PAX9 expression was an independent prognostic factor for decreased overall survival (P = 0.022)., Conclusions: Our results revealed that PAX9 expression defines an aggressive subset of LADs preferentially occurring in smokers that may arise from bronchial or bronchiolar cells., (© 2022 John Wiley & Sons Ltd.)

Objectives: Programmed death ligand 1 and 2 (PD-L1 and PD-L2) bind programmed death 1 (PD-1). PD-L1 is an established predictive biomarker of response to immunotherapies targeting PD-1 and PD-L1 in lung adenocarcinoma (LUAD). However, the clinical relevance of PD-L2 expression in patients with LUAD remains unclear; we aimed to examine this aspect using LUAD specimens., Materials and Methods: PD-L2 expression status was immunohistochemically evaluated in 980 surgically resected LUAD specimens. PD-L2 expression status was classified based on the tumor proportion score (TPS) as negative (<1%), weakly positive (1-49%), or strongly positive (≥50%). Correlations between PD-L2 and PD-L1 expression status, clinicopathological features, driver oncogene alterations (EGFR, KRAS, ALK, ROS1, and RET), and prognosis were also analyzed., Results: PD-L2 expression was negative in 720 (73%) of 980 LUADs, weakly positive in 190 (19%), and strongly positive in 70 (7%). The concordance rate between PD-L1 and PD-L2 expression was 60%. Male sex, smokers, tumors > 3 cm in size, high-grade tumors, tumors without EGFR mutation or ALK fusion, and tumors with KRAS mutation were more common in patients with PD-L2-positive tumors (TPS ≥ 1%) than in patients with PD-L2-negative tumors (TPS < 1%). PD-L2 expression was not associated with overall survival (OS) or relapse-free survival (RFS). However, positive PD-L2 expression tended to be associated with better OS/RFS in PD-L1-positive patients and worse OS/RFS in PD-L1-negative patients., Conclusions: PD-L2-positive LUADs showed biologically aggressive characteristics. PD-L2 expression status was not associated with survival outcomes, but tended to show contrasting prognostic impacts based on PD-L1 expression status., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: The prognostic role of the epidermal growth factor receptor (EGFR) mutation remains controversial, especially in early-stage lung adenocarcinoma with a solid appearance. We evaluated the oncological outcomes of clinical stage I (c-stage I) radiologically invasive lung adenocarcinoma by EGFR mutation status., Methods: Between 2008 and 2013, the data from 463 surgically resected c-stage I radiologically invasive, i.e. solid-dominant lung adenocarcinomas subjected to EGFR mutant analysis, were evaluated. Oncological outcomes were assessed using multivariable Cox regression analysis. Recurrence-free survival (RFS) was estimated using Kaplan-Meier analysis and the log-rank test., Results: A total of 229 (49%) samples harboured the EGFR-mutant adenocarcinoma. Overall, the 5-year RFS did not differ significantly between the EGFR-mutant and EGFR wild-type groups (67.3% vs 64.9%; P = 0.639). However, among the clinical T1c/T2a tumour subset (n = 177), a multivariable Cox hazard model revealed that radiologically pure-solid tumour (P = 0.024), EGFR-mutant (P = 0.027) and pathological stage II/III (P < 0.001) were significant predictors of a poor RFS. Furthermore, in the c-T1c/T2a radiologically pure-solid lung adenocarcinoma subset, the EGFR-mutant group showed marginally lower 5-year RFS compared to that with the EGFR wild-type group (n = 134; 34.9% vs 53.0%; P = 0.062). Among them, multivariable Cox regression analysis revealed that EGFR mutant (P = 0.037) and pathological stage II/III (P = 0.011) were independently and significantly prognostic for worse RFS., Conclusions: Among the c-stage I radiologically invasive lung adenocarcinomas, the EGFR mutation-positive type was correlated with an increased risk of recurrence in the c-T1c/T2a radiologically pure-solid tumour subset. When considering the prognostic value of EGFR mutations in early-stage lung adenocarcinoma, it is necessary to stratify them based on the presence of a ground-glass opacity component., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The clinicopathological differences among high-grade fetal lung adenocarcinomas completely comprising tumor cells that resemble fetal lung epithelium (pure type) and those with fetal lung-like components admixed with conventional adenocarcinoma cells (mixed type) remain undetermined. Here, we examined the clinicopathological, immunohistochemical, and molecular features of 11 lung adenocarcinomas with fetal lung-like morphology among 3895 consecutive cases of primary lung cancer based on the expression pattern of transcription factors. According to the current WHO classification, two cases (0.05%) were categorized as low-grade fetal adenocarcinoma, two cases (0.05%) were pure-type high-grade fetal adenocarcinoma, five cases (0.1%) were mixed-type high-grade fetal adenocarcinoma, and the remaining two cases (0.05%) were lung adenocarcinoma with high-grade fetal features (fetal lung-like morphology occupied less than 50%). CTNNB1 mutations were exclusively identified in low-grade fetal adenocarcinomas. In contrast, mixed-type high-grade fetal adenocarcinoma or lung adenocarcinoma with high-grade fetal features frequently harbored mitogenic drivers including EGFR mutations. Furthermore, almost all tumor cells expressed CDX2 and HNF4α in both cases of pure-type high-grade fetal lung adenocarcinoma, but lacked TTF-1 positivity. In contrast, TTF-1 was frequently expressed in mixed-type high-grade fetal lung adenocarcinoma and in lung adenocarcinoma with high-grade fetal features. Our data suggest similar prevalence of low-grade fetal lung adenocarcinoma and pure-type high-grade fetal lung adenocarcinoma, and indicate that pure- and mixed-type high-grade fetal lung adenocarcinomas are distinct, with the former akin to low-grade fetal adenocarcinoma with respect to purely embryonic morphology and absence of common lung adenocarcinoma mitogenic drivers, and the latter being genetically and transcriptionally related to conventional lung adenocarcinoma., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: We evaluated the oncological role of a ground-glass opacity (GGO) component in hypermetabolic lung adenocarcinoma with a high maximum standardized uptake value., Methods: Between 2008 and 2017, we retrospectively reviewed the data of surgically resected clinically node-negative lung adenocarcinomas with a hypermetabolic activity. Furthermore, they were classified based on the presence of GGO. The prognostic significance of a GGO in hypermetabolic tumours was evaluated using the Cox proportional-hazards model. The overall survival (OS) was estimated by the Kaplan-Meier method using a log-rank test., Results: Of the 1134 surgically resected clinically node-negative lung adenocarcinoma, 603 cases with hypermetabolic activity (maximum standardized uptake value ≥3.0 mg/dl) were evaluated. Among them, there were 120 (20%) cases in the With GGO group and 483 (80%) in the Solid group. The 5-year OS of patients with hypermetabolic lung adenocarcinoma was significantly different between the With GGO and Solid groups (83.1% vs 59.4%, P < 0.001). After stratifying by the presence of GGO, maximum standardized uptake value and maximum tumour size were independently significant prognosticators in the Solid group by multivariable analysis; however, no clinical factors were associated with survival among the With GGO group. The 5-year OS was favourable despite the solid component size among the With GGO group (T1a + T1b: 85.5%, T1c: 80.0%, T2a or more: 84.2%, P = 0.904). For the Solid group, survival diminished drastically with increasing tumour size (T1a + T1b: 68.7%, T1c: 62.8%, T2a or more: 48.0%, P < 0.001)., Conclusions: The prognosis of lung adenocarcinoma with GGO was favourable even in hypermetabolic tumours. Accordingly, the presence of GGO should be considered as an important parameter in the next clinical T classification., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker of response to immunotherapies targeting programmed death-1/PD-L1 in advanced-stage lung adenocarcinoma. The aim of this study was to investigate the associations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene alterations in patients with lung adenocarcinoma., Materials and Methods: We evaluated PD-L1 expression in 1,005 surgically resected lung adenocarcinoma specimens, by immunohistochemistry using the 22C3 antibody. PD-L1 positivity was defined based on the proportion of stained tumor cells (TPS) on tissue microarrays: <1% (negative), 1-49% (weakly positive), and ≥ 50% (strongly positive). Correlations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene (EGFR, KRAS, ALK, ROS1, and RET) alterations in lung adenocarcinoma were analyzed., Results: PD-L1 expression was negative in 726 (72%) of 1,005 tumors, weakly positive in 161 (16%), and strongly positive in 118 (12%). Male sex, smoking, elevated serum carcinoembryonic antigen levels, advanced pathological stages, high-grade tumors, predominantly solid tumors, tumors with lymphatic permeation or vascular or pleural invasion, tumors without EGFR mutations, and tumors with KRAS mutations were more common in patients with PD-L1-positive tumors (TPS ≥ 1%) than in those with PD-L1-negative tumors (TPS < 1%). PD-L1 positivity was not associated with ALK, ROS1, or RET fusion status. Although PD-L1 positivity was associated with poor overall survival and poor relapse-free survival in all patients, this was not statistically significant after adjusting for prognostic factors in the multivariate analysis. In the subgroup analysis according to driver oncogene alterations, PD-L1 positivity was associated with poor relapse-free survival only in patients with EGFR-mutated tumors., Conclusion: Surgically resected lung adenocarcinomas with increased PD-L1 expression were biologically aggressive tumors that frequently occurred in male smokers. PD-L1 expression and its prognostic significance differed according to driver oncogene alterations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

There are multiple transcription start sites (TSSs) in agreement with multiple transcript variants encoding different isoforms of NKX2-1/TTF-1 (thyroid transcription factor 1); however, the clinicopathological significance of each transcript isoform of NKX2-1/TTF-1 in lung adenocarcinoma (LAD) is unknown. Herein, TSS-level expression of NKX2-1/TTF-1 isoforms was evaluated in 71 LADs using bioinformatic analysis of cap analysis of gene expression (CAGE)-sequencing data, which provides genome-wide expression levels of the 5'-untranslated regions and the TSSs of different isoforms. Results of CAGE were further validated in 664 LADs using in situ hybridisation. Fourteen of 17 TSSs in NKX2-1/TTF-1 (80% of known TSSs in FANTOM5, an atlas of mammalian promoters) were identified in LADs, including TSSs 1-13 and 15; four isoforms of NKX2-1/TTF-1 transcripts (NKX2-1&#95;001, NKX2-1&#95;002, NKX2-1&#95;004, and NKX2-1&#95;005) were expressed in LADs, although NKX2-1&#95;005 did not contain a homeodomain. Among those, six TSSs regulated NKX2-1&#95;004 and NKX2-1&#95;005, both of which contain exon 1. LADs with low expression of isoforms from TSS region 11 regulating exon 1 were significantly associated with poor prognosis in the CAGE data set. In the validation set, 62 tumours (9.3%) showed no expression of NKX2-1/TTF-1 exon 1; such tumours were significantly associated with older age, EGFR wild-type tumours, and poor prognosis. In contrast, 94 tumours, including 22 of 30 pulmonary invasive mucinous adenocarcinomas (IMAs) exhibited exon 1 expression without immunohistochemical TTF-1 protein expression. Furthermore, IMAs commonly exhibited higher exon 1 expression relative to that of exon 4/5, which contained a homeodomain in comparison with EGFR-mutated LADs. These transcriptome and clinicopathological results reveal that LAD use at least 80% of NKX2-1 TSSs and expression of the NKX2-1/TTF-1 transcript isoform without exon 1 (NKX2-1&#95;004 and NKX2-1&#95;005) defines a distinct subset of LAD characterised by aggressive behaviour in elder patients. Moreover, usage of alternative TSSs regions regulating NKX2-1&#95;005 may occur in subsets of LADs., (© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)

Aims: In the evolving era of precision medicine, increasing emphasis is placed on detecting molecular alterations driving the development of specific cancers and targeting them with matched therapies that can yield the best outcomes for patients. Lung adenocarcinomas with uncommon actionable alterations, including MET exon 14 skipping (METex14), ERBB2 and BRAF mutations, are rare and poorly characterised cancers., Methods and Results: To more clearly understand the histopathological features of lung adenocarcinoma with uncommon actionable alterations, we compared the histological features of 678 cases with mitogenic driver alterations from 996 surgically resected lung adenocarcinomas. Genomic data from our cohort revealed METex14, ERBB2 and BRAF mutations in 13, 16 and 15 cases, respectively. Patients who had lung adenocarcinoma with METex14 were often elderly females. Histological features such as clear cell features (23%), hyaline globules (31%) and nuclear pleomorphism (39%) were the most frequently identified in METex14-positive cases; among those, three cases (23%) had tumour cells with bizarre giant or multilobulated nuclei. Additionally, the micropapillary pattern was the most frequently identified in ERBB2-mutated lung adenocarcinoma (31%). Lung adenocarcinoma with BRAF mutations tended to be less invasive, and the BRAF V600E mutation was identified in only one case with lepidic adenocarcinoma. Immunohistochemically, all METex14, ERBB2 and BRAF-positive tumours, except for invasive mucinous adenocarcinoma, were positive for thyroid transcription factor 1 (TTF-1)., Conclusions: Our data from Japanese patients showed that lung adenocarcinoma with METex14 had unique clinicopathological characteristics: tumour cells with marked nuclear pleomorphism, hyaline globules and expression of TTF-1 in elderly women who never or lightly smoked., (© 2020 John Wiley & Sons Ltd.)

The extensive clinical applications of next-generation sequence analyzers have made uncommon and compound EGFR mutations more prevalent than previously described. However, clinicopathological impacts of compound EGFR mutations in lung adenocarcinoma remain unclear. We earlier examined the presence of compound EGFR mutations primarily in the cis allele by EGFR exon sequencing and droplet digital polymerase chain reaction in 462 completely resected EGFR-mutated adenocarcinomas of the lung and identified 64 tumors with compound mutations. We evaluated clinicopathological characteristics of lung adenocarcinomas with compound EGFR mutations in comparison with cases with common or uncommon single mutations. Among 64 compound EGFR mutations, L858R/E709G (9%) was the most frequent mutation type, followed by L858R/S768I (8%), L858R/T790M (8%), and L858R/L833V (6%). We observed both single and compound mutations frequently in women, never or light smokers; their adenocarcinomas showed thyroid transcription factor-1 immunoreactivity. In contrast, compound mutations were significantly associated with lymph node metastases (p = 0.0242; single vs. compound cases) and the presence of tumor cells with clear cytoplasm (p = 0.0014; single vs. compound cases). Furthermore, patients with compound mutations had significantly poorer prognoses than cases with single EGFR mutations (p = 0.043). Overall, clinicopathological features of common, uncommon, and compound EGFR mutations are similar; however, tumors with compound mutations may be characterized by aggressive behavior and histological findings of clear cell features., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to identify patients with pathological stage I lung adenocarcinoma at high risk of recurrence., Methods: We retrieved data from 536 patients with pathological stage I lung adenocarcinoma who underwent lobectomy and were enrolled in a prospective multiinstitutional study (the JCOG0201 study). Invasive component size, excluding lepidic component, was used as the tumor size. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier method, and a multivariable Cox proportional hazards model identified independent prognostic factors associated with worse RFS., Results: The all-patient 10-year RFS was 83.9% (median follow-up 10.2 years). Multivariable Cox analysis revealed that age greater than 65 years (hazard ratio [HR], 2.60; 95% confidence interval (CI), 1.66-4.07), invasive component size greater than 2 cm (HR, 2.70; 95% CI, 1.40-5.23), visceral pleural invasion (HR, 2.17; 95% CI, 1.23-3.81), and vascular invasion (HR, 2.59; 95% CI, 1.47-4.55) were potential independent prognostic factors for RFS. When patients were divided into a high-risk group for recurrence (invasive component size >2 cm or positive for visceral pleural invasion or for vascular invasion; n = 124) and a low-risk group (invasive component size ≤2 cm and negative for visceral pleural invasion and vascular invasion; n = 408), there was a significant difference in RFS between the high-risk and low-risk groups (high-risk group: HR, 3.61; 95% CI, 2.35-5.55)., Conclusions: Pathological stage I lung adenocarcinoma patients with an invasive component size greater than 2 cm, visceral pleural invasion, or vascular invasion were at high risk for recurrence., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: It is evident that the frequency of nodal metastasis in part-solid lung adenocarcinoma is significantly low. For those cases, the prognostic impact of the lymph node dissection (LND) is highly controversial., Methods: We reviewed 462 clinical stage I radiologic part-solid lung adenocarcinoma patients who underwent lobectomy or segmentectomy with lymphadenectomy. Consolidation tumor ratio was evaluated for all patients. Extent of LND was classified into systematic/lobe-specific mediastinal LND (m-LND) and hilar LND only (h-LND). Prognostic significance of LND was assessed by a multivariable analysis using propensity score matching. Survival was calculated by the Kaplan-Meier method using the log rank test., Results: The m-LND was performed in 314 patients (68%), and h-LND in 148 (32%). Overall survival (OS) was not significantly different between m-LND and h-LND (5-year OS, 94.2% versus 92.8%, p = 0.585), as shown in 92 matched pairs (5-year OS, 94.0% versus 93.2%, p = 0.845). Cox proportional hazards model revealed maximum standardized uptake value as an independently significant oncologic prognosticator (p = 0.003), but extent of LND was not (p = 0.997). Nodal involvement was found in 16 patients, and was exclusive in solid-dominant lesions (ie, 0.5 less than consolidation tumor ratio of 1.0 or less; 4.9%). Multivariable analysis revealed carcinoembryonic antigen and maximum standardized uptake value as significant predictors of nodal metastasis among solid-dominant lesions (0.001, 0.002). For 329 solid-dominant lesions (71%), however, survival was similar between m-LND and h-LND (5-year OS, 93.2% versus 87.1%, p = 0.097), and was proven in 58 matched pairs (5-year OS, 82.9% versus 82.9%, p = 0.822)., Conclusions: Extent of LND was not associated with survival outcome of part-solid lung adenocarcinoma. Furthermore, it had no influence on the prognosis even for solid-dominant lesions by propensity score analysis, which could be selectively omitted based on both preoperative variables including carcinoembryonic antigen or maximum standardized uptake value., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Epidermal growth factor receptor (EGFR) gene mutation status is a well-established predictor of the efficacy of EGFR tyrosine-kinase inhibitor (TKI) therapy in patients with non-small cell lung cancer. Recently, differences in EGFR mutation subtypes have been reported to be associated with the efficacy of EGFR-TKI therapy. The prognostic impact of EGFR mutation status and subtypes remains controversial, however., Methods: We retrospectively reviewed 939 patients with surgically resected adenocarcinomas who underwent EGFR mutation status analysis between January 2010 and December 2014. Overall survival (OS) and recurrence-free survival (RFS) were compared according to pathological stage, EGFR mutation status, and EGFR mutation subtype using the log-rank test. Independent prognostic factors for OS and RFS were identified by multivariate analysis using the Cox proportional hazards model., Results: The median duration of follow-up was 48 months. We found that positive EGFR mutation status was significantly associated with longer OS and RFS in all patients and was associated with longer OS in patients in pathological stage I; however, there were no significant differences in OS and RFS between patients with exon 21 L858R mutations and those with exon 19 deletions. In a Cox regression model for OS, EGFR mutation status was a significant prognostic factor that was independent of well-established prognostic factors, including age, pathological stage, vascular invasion, lymphatic permeation, and serum carcinoembryonic antigen level., Conclusions: Positive EGFR mutation status is a favorable prognostic factor in patients with surgically resected lung adenocarcinomas; however, EGFR mutation subtype (exon 21 L858R mutation or exon 19 deletion) exhibits no prognostic impact., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)