Journal of Pathology and Translational Medicine

Original Articles

Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing: Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2022;56(5):249-259. Published online September 13, 2022; DOI: https://doi.org/10.4132/jptm.2022.06.11

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Background
Activating mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are predictive biomarkers for response to EGFR–tyrosine kinase inhibitor (TKI) therapy in lung adenocarcinoma (LUAD). Here, we characterized the clinicopathologic features associated with EGFR mutations via peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper) and evaluated the feasibility of targeted deep sequencing for detecting the mutations.
Methods
We examined EGFR mutations in exons 18 through 21 for 2,088 LUADs from July 2017 to April 2020 using PANAMutyper. Of these, we performed targeted deep sequencing in 73 patients and evaluated EGFR-mutation status and TKI clinical response.
Results
EGFR mutation was identified in 55.7% of LUADs by PANAMutyper, with mutation rates higher in females (69.3%) and never smokers (67.1%) and highest in the age range of 50 to 59 years (64.9%). For the 73 patients evaluated using both methods, next-generation sequencing (NGS) identified EGFR mutation–positive results in 14 of 61 patients (23.0%) who were EGFR-negative according to PANAMutyper testing. Of the 10 patients reportedly harboring a sensitizing mutation according to NGS, seven received TKI treatment, with all showing partial response or stable disease. In the 12 PANAMutyper-positive cases, NGS identified two additional mutations in exon 18, whereas a discordant negative result was observed in two cases.
Conclusions
Although PANAMutyper identified high frequencies of EGFR mutations, targeted deep sequencing revealed additional uncommon EGFR mutations. These findings suggested that appropriate use of NGS may benefit LUAD patients with otherwise negative screening test results.

Citations

Citations to this article as recorded by

Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
Pathology.2024; 56(5): 653. CrossRef
Histo-pillar strip for optimal histogel block construction and biomarker analysis in 3D-lung cancer patient-derived organoids
Sang-Yun Lee, Eunyoung Lee, Ji-O Ryu, Kyuhwan Kim, Yongki Hwang, Bosung Ku, Seok Whan Moon, Mi Hyoung Moon, Kyung Soo Kim, Kwanyong Hyun, Jeong Uk Lim, Chan Kwon Park, Sung Won Kim, Chang Dong Yeo, Dong Woo Lee, Seung Joon Kim
Biofabrication.2024; 16(4): 045017. CrossRef

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma: Tripti Nakra, Varsha Singh, Aruna Nambirajan, Prabhat Singh Malik, Anant Mohan, Deepali Jain; J Pathol Transl Med. 2021;55(4):279-288. Published online July 8, 2021; DOI: https://doi.org/10.4132/jptm.2021.05.10

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Abstract PDF

Background
Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort.
Methods
This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the
results
were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed.
Conclusions
Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

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Mutation profile and programmed death ligand 1 status of patients with non‐small cell lung cancer diagnosed with “adenocarcinoma” and “non‐small cell carcinoma favor adenocarcinoma”
Naoko Shigeta, Tomoyuki Yokose, Shuji Murakami, Tetsuya Isaka, Kanako Shinada, Emi Yoshioka, Atsuya Narita, Kengo Katakura, Tetsuro Kondo, Terufumi Kato, Takuya Nagashima, Haruhiro Saito, Hiroyuki Ito
Thoracic Cancer.2024; 15(6): 458. CrossRef
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Expression landscapes in non-small cell lung cancer shaped by the thyroid transcription factor 1
Herdee Gloriane C. Luna, Marcelo Severino Imasa, Necy Juat, Katherine V. Hernandez, Treah May Sayo, Gloria Cristal-Luna, Sheena Marie Asur-Galang, Mirasol Bellengan, Kent John Duga, Bien Brian Buenaobra, Marvin I. De los Santos, Daniel Medina, Jamirah Sam
Lung Cancer.2023; 176: 121. CrossRef
Malignant pleural effusion cell blocks are reliable resources for PD-L1 analysis in advanced lung adenocarcinomas: a concordance study with matched histologic samples
Swati Mahajan, Aruna Nambirajan, Ishan Gupta, Nalini Gupta, Parikshaa Gupta, Deepali Jain
Journal of the American Society of Cytopathology.2022; 11(5): 253. CrossRef
Clinicopathologic Features and Molecular Biomarkers as Predictors of Epidermal Growth Factor Receptor Gene Mutation in Non-Small Cell Lung Cancer Patients
Lanlan Liu, Xianzhi Xiong
Current Oncology.2021; 29(1): 77. CrossRef

Case Study

A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma: Ki-Chang Lee, Jiwon Koh, Doo Hyun Chung, Yoon Kyung Jeon; J Pathol Transl Med. 2021;55(2):139-144. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.16

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Abstract PDF

Rare cases of lung adenocarcinoma (LUAD) with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation have been reported. However, their clonal and evolutional relationship remains unclear. We report a case of early-stage EGFR-mutated LUAD with a focal concomitant EGFR/ALK alteration. A 63-year-old male underwent lobectomy to remove a 1.9-cm-sized lung nodule, which was diagnosed with EGFR-mutated LUAD. ALK immunohistochemistry (IHC) showed focal positivity within the part of the tumor characterized by lepidic pattern, also confirmed by fluorescence in-situ hybridization (FISH). Targeted next-generation sequencing was performed separately on the ALK IHC/FISH-positive and -negative areas. EGFR L833V/L858R mutations were detected in both areas, whereas EML4 (echinoderm microtubule-associated protein-like 4)-ALK translocations was confirmed only in the ALK IHC/FISH-positive area, suggesting the divergence of an EGFR/ALK co-altered subclone from the original EGFR-mutant clone. Our study suggests that concurrent alterations of EGFR and ALK can arise via divergent tumor evolution, even in the relatively early phases of tumorigenesis.

Citations

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Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps
Yanhua Zuo, Guangyi Leng, Ping Leng
Pathology and Oncology Research.2023;[Epub] CrossRef
Machine Learning-Based Integration Develops a Macrophage-Related Index for Predicting Prognosis and Immunotherapy Response in Lung Adenocarcinoma
Zuwei Li, Minzhang Guo, Wanli Lin, Peiyuan Huang
Archives of Medical Research.2023; 54(7): 102897. CrossRef
Big data analysis identified a telomere-related signature predicting the prognosis and drug sensitivity in lung adenocarcinoma
Weiyi Zhang
Medicine.2023; 102(46): e35526. CrossRef

Review

Liquid biopsy using extracellular vesicle–derived DNA in lung adenocarcinoma: In Ae Kim, Jae Young Hur, Hee Joung Kim, Seung Eun Lee, Wan Seop Kim, Kye Young Lee; J Pathol Transl Med. 2020;54(6):453-461. Published online October 8, 2020; DOI: https://doi.org/10.4132/jptm.2020.08.13

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Abstract PDF

Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%–60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult. Extracellular vesicles (EVs) are ideal carriers of cancer biomarkers, as cancer cells secret an abundance of EVs, and the contents of tumor cell-originated EVs reflect the molecular and genetic composition of parental cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and tumor-specific oncogenic mutant DNAs. For these reasons, liquid biopsy using EV DNA has the potential to overcome issues arising from tissue shortages associated with small biopsies, which are often seen in lung cancer patients, and the biopsy product can be used in other diagnostic methods, such as epidermal growth factor receptor (EGFR) mutation testing and next-generation sequencing (NGS). A higher sensitivity can be achieved when EV DNAs obtained from bronchoalveolar lavage fluid (BALF) are used rather than those from blood. BALF, when obtained close to the tumor site, is a promising liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the tumor microenvironment, and provides increased diagnostic sensitivity when compared to blood.

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Nanobiotechnology: A smart platform of the future transform liquid biopsy era
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Irène Tatischeff
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In-Cell Labeling Coupled to Direct Analysis of Extracellular Vesicles in the Conditioned Medium to Study Extracellular Vesicles Secretion with Minimum Sample Processing and Particle Loss
Anissa Viveiros, Vaibhavi Kadam, John Monyror, Luis Carlos Morales, Desmond Pink, Aja M. Rieger, Simonetta Sipione, Elena Posse de Chaves
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Cristina Catoni, Veronica Di Paolo, Elisabetta Rossi, Luigi Quintieri, Rita Zamarchi
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DNA-Loaded Extracellular Vesicles in Liquid Biopsy: Tiny Players With Big Potential?
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Cancers.2021; 13(15): 3827. CrossRef
Bronchoalveolar Lavage as a Potential Diagnostic Specimens to Genetic Testing in Advanced Lung Cancer
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International Journal of Molecular Sciences.2020; 21(22): 8550. CrossRef

Original Article

The Expression of Adipophilin Is Frequently Found in Solid Subtype Adenocarcinoma and Is Associated with Adverse Outcomes in Lung Adenocarcinoma: Sun Ah Shin, Hee Young Na, Ji Young Choe, Doohyun Chung, Mira Park, Sohee Oh, Ji Eun Kim; J Pathol Transl Med. 2018;52(6):357-362. Published online October 4, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.13

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Abstract PDF

Background
The up-regulation of the lipogenic pathway has been reported in many types of malignant tumors. However, its pathogenic role or clinical significance is not fully understood. The objective of this study was to examine the expression levels of adipophilin and related hypoxic signaling proteins and to determine their prognostic impacts and associations with the pathologic characteristics of lung adenocarcinoma.
Methods
Expression levels of adipophilin, heat shock protein 27 (HSP27), carbonic anhydrase IX, and hypoxia-inducible factor 1α were examined by immunohistochemical staining using tissue microarray blocks. Correlations between protein expression levels and various clinicopathologic features were analyzed.
Results
A total of 230 cases of primary adenocarcinoma of the lung were enrolled in this study. Adipophilin expression was more frequent in males and with the solid histologic type. It was correlated with HSP27 expression. Patients with adipophilin-positive adenocarcinoma showed a shorter progression-free survival (PFS) (median PFS, 17.2 months vs 18.4 months) in a univariable survival analysis, whereas HSP27 positivity correlated with favorable overall survival (OS) and PFS. In a multivariable analysis, adipophilin and HSP27 were independent prognostic markers of both OS and PFS.
Conclusions
Activated lipid metabolism and the hypoxic signaling pathway might play a major role in the progression of lung adenocarcinoma, especially in the solid histologic type.

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Journal of Clinical Pathology.2024; 77(10): 676. CrossRef
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The International Journal of Biological Markers.2023; 38(1): 3. CrossRef
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Maisoon Matareed, Eleftheria Maranou, Saara A Koskela, Arfa Mehmood, Helen Kalirai, Sarah E Coupland, Carlos R Figueiredo
The Journal of Pathology.2023; 260(2): 203. CrossRef
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Laboratory Investigation.2020; 100(5): 727. CrossRef
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Virchows Archiv.2020; 477(2): 291. CrossRef

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