scholarly journals Clinicopathological, Radiological, and Molecular Features of Primary Lung Adenocarcinoma with Morule-Like Components

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Li-Li Wang ◽  
Li Ding ◽  
Peng Zhao ◽  
Jing-Jing Guan ◽  
Xiao-Bin Ji ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Pik3ca Mutation ◽  
Gene Mutations ◽  
Invasive Adenocarcinoma ◽  
Targeted Next Generation Sequencing ◽  
Molecular Features ◽  
Solid Nodule ◽  
Primary Lung Adenocarcinoma ◽  
Lung Adenocarcinomas

Background. Morule-like component (MLC) was a rare structure in primary lung adenocarcinoma. We aimed to reveal the clinicopathological, radiological, immunohistochemical, and molecular features of lung adenocarcinoma with MLCs. Methods. Twenty lung adenocarcinomas with MLCs were collected, and computed tomographic and histological documents were reviewed. Immunohistochemistry, targeted next-generation sequencing, and Sanger sequencing for β-catenin gene were performed. Results. There were 9 lepidic adenocarcinomas, 8 acinar adenocarcinomas, 2 papillary adenocarcinomas, and 1 minimally invasive adenocarcinoma. Most patients (16/17) were shown a pure solid nodule, and 1 patient was shown a partly solid nodule on chest computed tomography (CT). Nine cases were accompanied with micropapillary components, and 3 were with cribriform components in which 2 suffered a worse prognosis. No significant association was found between the MCLs and the overall survival of lung adenocarcinoma ( P = 0.109 ). The MLCs were often arranged in whorled or streaming patterns. The cells in MLCs showed syncytial and mild appearance. The MLCs were positive for E-cadherin, CK7, TTF-1, napsin-A, vimentin, and β-catenin (membrane), and negative for CK5/6, p40, p63, Synaptophysin, chromogranin A, and Cdx-2. EGFR mutation, ALK-EML4 fusion, HER2 amplification, and PIK3CA mutation were detected in 16 cases, 2 cases, 1 case, and 1 case, respectively. EGFR mutation was more frequent in adenocarcinomas with MLCs than those without MLCs ( P = 0.040 ). β-catenin gene mutation was not detected in any patients. Conclusions. MLC is often observed in the background of acinar, lepidic, and papillary adenocarcinomas. Lung adenocarcinomas with MLCs tend to appear as a solid mass on CT and harbor EGFR gene mutations. The micropapillary components and cribriform components may cause poor prognosis of lung adenocarcinomas with MLCs. Vimentin is always positive in MLCs, and it is a useful marker for the identification of MLCs.

scholarly journals Cell-free DNA From Pleural Effusion Samples: Is It Right for Molecular Testing in Lung Adenocarcinoma?

2021 ◽  
Vol 27 ◽  
Author(s):  
Attila Mokánszki ◽  
Emese Sarolta Bádon ◽  
Anikó Mónus ◽  
László Tóth ◽  
Nóra Bittner ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Gene Mutations ◽  
Molecular Testing ◽  
Alternative Source ◽  
Cell Free Dna ◽  
Molecular Features ◽  
Free Dna ◽  
Mutational Status ◽  
Therapeutic Decisions

Pathogenic molecular features gained specific significance in therapeutic decisions in lung carcinoma in the past decade. Initial and follow up genetic testing requres appropriate amounts and quality of tumor derived DNA, but tumor sampling, especially for disease monitoring is generally limited. Further to the peripheral blood (PB), samples from pleural fluid, accumulating in diverse lung processes might serve as an alternative source for cell-free DNA (cfDNA) for genetic profiling. In our study, cfDNA isolated from the pleural effusion and from the PB, and genomic DNA (gDNA) obtained from tissue/cellular samples were analyzed and compared from altogether 65 patients with pulmonary disease, including 36 lung adenocarcinomas. The quantity of effusion cfDNA yield appeared to be significantly higher compared to that from simultaneously collected PB plasma (23.2 vs. 4.8 ng/μl, p < 0.05). Gene mutations could be safely demonstrated from the effusion cfDNA fraction obtained from adenocarcinoma patients, 3/36 EGFR, 9/36 KRAS and 1/36 BRAF gene variants were detected. In this series, 9/13 samples showed an effusion+/plasma-mutational status, while only 1/13 samples presented with the opposite findings (effusion-/plasma+). gDNA analysis from sediment cell blocks from the identical effusion sample was surprisingly ineffective for lung adenocarcinoma profiling due to the low DNA yield. In conclusion, the cell free supernatant of pleural effusions appears to concentrate cancer derived cfDNA and seems to be particularly suitable for serial genotyping of pulmonary adenocarcinoma.

Clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20588-e20588
Author(s):  
Linping Gu ◽  
Bei Zhang ◽  
Ding Zhang ◽  
Hong Jian
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
De Novo ◽  
Egfr Mutations ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Genetic Characteristics ◽  
Egfr Mutant ◽  
Lung Adenocarcinomas ◽  
Egfr T790m

e20588 Background: Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of the resistance mechanism of EGFR tyrosine kinase inhibitors. However, the clinical course of transformed SCLC and the difference of genomic profiling between de novo SCLC patients and transformed SCLC patients are still poorly characterized. Methods: Patients from our hospital diagnosed with SCLC were enrolled retrospectively in this study, including de novo SCLC patients and SCLC patients transformed from EGFR-mutant lung adenocarcinomas. Genomic profiling was performed on formalin-fixed paraffin-embedded tumor samples by next generation sequencing (NGS). In statistical analysis, fisher ‘exact test was used. All tests were bilateral, with P<0.05 indicating significant statistical difference. Results: In total, 16 patients with SCLC transformed from EGFR-mutant lung adenocarcinomas and 230 de novo SCLC patients were included in our study. Transformed SCLC patients were more in younger (p=0.007), female (p<0.001) and non-smokers (p<0.001) than de novo SCLC patients. In transformed SCLC patients, 12 patients (75%) occurred SCLC transformation within 2 years after the lung adenocarcinomas diagnosis. Median transformation time was 20 months. During the treatment of adenocarcinomas, the overall response rate (ORR) was 75% and the median progression-free survival was 12 months. After the initiation of SCLC therapy, the ORR of 1st line chemotherapy was 40%. For the genomic profiling, EGFR mutations, including exon 19 deletion (56%), L858R (38%), and others (6%), were detected. 11 patients with acquired resistance were received EGFR T790M test, 82% of patients had acquired EGFR T790M mutation. 11 patients after transformation to SCLC had NGS test, 100% maintained their founder EGFR mutation, and other recurrent mutations included TP53, RB1 and EGFR amplification. Compared with the genetic alterations in de novo SCLC patients, TP53 mutations were significantly decreased (p=0.006) while EGFR mutations were significantly elevated (p<0.001) in transformed SCLC patients. However, no significant difference on RB1, ALK and ROS1 mutations were observed. Interestingly, a 60-year-old woman in our transformed SCLC cohort harbored EGFR 19 del mutant at allele frequency of 50.39%，she received osimertinib plus epirubicin/cyclophosphamide as 1st line treatment and reached partial response, with survival of 4 years to date. Conclusions: We demonstrated the clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC and found one patient still benefited from EGFR-TKI. Our study suggested that SCLC patients with EGFR mutation who transformed from lung adenocarcinoma may be potential benefit population using EGFR inhibitors.

Does EGFR mutation define the histological predominant subtype of lung adenocarcinoma?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7557-7557
Author(s):  
Eri Sugiyama ◽  
Koichi Goto ◽  
Genichiro Ishii ◽  
Tomohiro Haruki ◽  
Shingo Matsumoto ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Heavy Smoker ◽  
Cancer Center ◽  
Histological Subtypes ◽  
Invasive Adenocarcinoma ◽  
Predominant Subtype ◽  
Egfr Tyrosine Kinase Inhibitors

7557 Background: In 2011, invasive adenocarcinomas were newly classified into the five predominant subtypes by IASLC/ATS/ERS: lepidic, papillary, acinar, micropapillary, and solid. The purpose of this study is to investigate the correlation between EGFRmutation and the histological predominant subtype of lung adenocarcinoma. Methods: Among a total of 1,736 patients with lung adenocarcinoma who underwent surgical resection from 2002 to 2011 in National Cancer Center Hospital East, 1,507 were classified into invasive adenocarcinoma. 526 of whom were examined EGFR mutation status. Histological predominant subtypes were evaluated at the maximum cut surface of tumors. The EGFR mutation analysis was performed by PCR-invader method. Treatment efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in 73 relapsed patients with EGFRmajor mutations were also examined. Results: 526 adenocarcinomas were consisted of 95 lepidic (18%), 221 papillary (42%), 80 acinar (15%), 9 micropapillary (2%), and 121 solid predominant subtype (23%). EGFR mutations were detected in 227 adenocarcinomas (43%), and its frequency in the solid subtype (22%) was significantly less than that of other histological subtypes (lepidic 47%, papillary 53%, and acinar 44%; P < 0.01). The proportion of minor mutations, other than exon 21 L858R and exon 19 deletions, were significantly higher in the solid subtype (22%) than that of the others (lepidic 4%, and papillary 12%; P < 0.01). In 73 patients with EGFR major mutations treated by EGFR-TKIs, the response rate was not different between histological subtypes (lepidic 86%, papillary 76%, acinar 89%, and solid 60%). Conclusions: The correlation between histological predominant subtypes of lung adenocarcinoma and the presence of EGFR mutations or the efficacy of EGFR-TKI were not identified in this study. Little is known about the reason why EGFR minor mutations were highly detected in the solid subtype of adenocarcinoma, however it is possibly due to the high frequency of heavy smokers in solid subtype (heavy smoker: solid 67% vs. others 27-44%).

Coexistence of rearranged during transfection (RET) variants and activating EGFR mutations with their molecular implications in lung adenocarcinomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20610-e20610
Author(s):  
Jeong-Oh Kim ◽  
Jung-Young Shin ◽  
Min Young Kim ◽  
Kyoung Hwa Son ◽  
Chan-Kwon Jung ◽  
...  
Keyword(s):  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Fusion Gene ◽  
Signaling Molecules ◽  
Egfr Mutations ◽  
Downstream Signaling ◽  
Tumor Tissues ◽  
Resected Tumor ◽  
Lung Adenocarcinomas

e20610 Background: RET rearrangements have been identified in 1-2% of lung adenocarcinomas. The most common fusion is the KIF5B-RET, the function and roles of the RET fusion oncogene, and its downstream signaling molecules remain unclear. Methods: We constructed a tissue microarray (TMA) comprising 581 resected tumor tissues from lung adenocarcinoma patients and investigated them using FISH with RET break-apart and KIF5B-RET SY translocation probes. NanoString’s nCounter technology was used to assay RETtranscripts. We evaluated the protein expressions of RET and RET-related signaling molecules, including p-AKT and p-ERK, using TMA-based IHC staining. Results: Using FISH, we identified 51 cases (8.8%) of RET variants and 10 cases (1.7%) of KIF5B-RET fusion genes among the 581 cases. RET protein expression was lower in the group harboring KIF5B-RET fusion gene than that in the group harboring a wild type RET gene. We found the activating EGFR mutations in 11 (21.6%) cases of 51 RET variants. For the group with KIF5B-RET fusion gene, the expression of p-ERK was significantly lower in EGFR mutation subgroup with presence of RET protein compared to EGFR mutation subgroup with absence of RET protein. For the group with RET rearrangement, there were significant differences in the expression level of p-AKT (P = 0.028) and, p-ERK protein expression was remarkably increased, especially in cases with no RET protein expression. Conclusions: Taken together, the expression of p-ERK protein was meaningfully increased in the RET variants group regardless of RET protein expression. This result suggests that RET inhibitors combined with ERK inhibitors may be an effective treatment strategy for lung adenocarcinoma patients harboring the RET variants.

scholarly journals Detection of EGFR Mutation of Pulmonary Adenocarcinoma in Sputum using Droplet Digital PCR

2021 ◽  
Author(s):  
Tetsuya Isaka ◽  
Tomoyuki Yokose ◽  
Hiroyuki Ito ◽  
Haruhiko Nakayama ◽  
Yohei Miyagi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Tumor Size ◽  
Mutation Detection ◽  
Egfr Mutation ◽  
Lung Tumor ◽  
Primary Lung Cancer ◽  
Resected Specimen ◽  
Sputum Cytology ◽  
Primary Lung Adenocarcinoma

Abstract Background】It is still unclear whether epidermal growth factor receptor (EGFR) mutation of primary lung adenocarcinoma can be detected accurately on sputum samples. This study aimed to examine EGFR mutations of primary lung adenocarcinoma in sputum samples using droplet digital polymerase chain reaction (ddPCR) and compare it with an EGFR mutation in surgically resected lung cancer. 【Methods】Sputum was collected preoperatively from patients with primary lung cancer who were scheduled for complete resection of lung tumor at Kanagawa Cancer Center from September 2014 to May 2016. ddPCR was performed to detect EGFR exon 21 L858R point mutation (Ex21 mutation) and EGFR exon 19 deletion mutation (Ex19 mutation) in the sputum samples. The concordance of EGFR mutation status in sputum samples and tumors in surgically resected specimen was evaluated for each positive and negative cytology group.【Results】One hundred and eighteen patients with primary lung adenocarcinoma provided sputum samples. Sputum cytology was positive in 13 patients (11.0%). ddPCR detected two cases of Ex21 mutation and two cases of Ex19 mutation. Compared to surgically resected specimens, the sensitivity, specificity, and positive predictive value of EGFR mutation detection were 80.0%, 100%, and 92.3%, respectively. The sensitivity of EGFR mutation detection was 3.1% in sputum cytology negative cases. Logistic regression model analysis revealed that tumor size ≥ 29 mm determined using computed tomography (CT) was an independent potential predictive factor for positive sputum cytology (odds ratio = 10.6, 95% confidence interval: 1.85–61.0, p=0.008).【Conclusions】EGFR mutation of primary lung adenocarcinoma was accurately detected in sputum samples using ddPCR if the sputum cytology was positive. Sputum samples should be collected in patients with CT tumor size ≥ 29 mm for EGFR mutation analysis.

scholarly journals Targeted Next-Generation Sequencing Analysis for Recurrence in Early-Stage Lung Adenocarcinoma

2020 ◽  
Author(s):  
In Ae Kim ◽  
Jae Young Hur ◽  
Hee Joung Kim ◽  
Jung Hoon Park ◽  
Jae Joon Hwang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
Early Stage ◽  
Genetic Alterations ◽  
Smoking History ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Targeted Ngs ◽  
Generation Sequencing

Abstract Background Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20–50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify genetic alterations that can predict recurrence, by comparing the molecular profiles of patient groups with and without recurrence. Methods Tissues from 230 patients with resected stage I–II lung adenocarcinoma (median follow-up: 49 months) were analyzed via targeted NGS for 207 cancer-related genes. The recurrence-free survival according to the number and type of mutation was estimated using the Kaplan–Meier method. Independent predictive biomarkers related to recurrence were identified using the Cox proportional hazards model. Results Recurrence was observed in 64 patients (27.8%). In multivariate analysis adjusted for age, sex, smoking history, stage, surgical mode, and visceral pleural invasion, the CTNNB1 mutation and fusion genes (ALK, ROS1, RET) were negative prognostic factors for recurrence in early-stage lung adenocarcinoma (HR 4.47, p = 0.001; HR 2.73, p = 0.009). EGFR mutation was a favorable factor (HR 0.51, p = 0.016), but the CTNNB1/EGFR co-mutations were negative predictors (HR 19.2, p < 0.001). TP53 mutation was a negative predictor compared with EGFR mutation for recurrence (HR 5.24, p = 0.02). Conclusions: Targeted NGS can provide valuable information to predict recurrence and identify patients at high recurrence risk, facilitating selection of the treatment strategy among close monitoring and adjuvant-targeted therapy. Larger datasets are required to validate these findings.

Primary lung adenocarcinoma with morule-like components: A unique histologic hallmark of aggressive behavior and EGFR mutation

Lung Cancer ◽  
2014 ◽  
Vol 85 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Koji Tsuta ◽  
Mitsumasa Kawago ◽  
Akihiko Yoshida ◽  
Shigeki Sekine ◽  
Hisao Asamura ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Aggressive Behavior ◽  
Egfr Mutation ◽  
Primary Lung Adenocarcinoma
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