Copy number gain in recurrent anaplastic lymphoma kinase (ALK ) rearrangement-lung adenocarcinoma in the pleural effusion

2018 ◽  
Vol 46 (9) ◽  
pp. 744-747
Author(s):  
Hideyuki Abe ◽  
Akihiko Kawahara ◽  
Koichi Azuma ◽  
Yuichi Murakami ◽  
Yorihiko Takase ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Anaplastic Lymphoma Kinase ◽  
Copy Number ◽  
Copy Number Gain ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma

Molecular profiling of lung adenocarcinoma using pleural effusion specimens.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21709-e21709
Author(s):  
Wei Zhang ◽  
Bei Zhang ◽  
Yifan Zhou ◽  
Xiaochen Zhao ◽  
Yuezong Bai
Keyword(s):  
Targeted Therapy ◽  
Next Generation Sequencing ◽  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Copy Number ◽  
Copy Number Gain ◽  
Molecular Profiling ◽  
Copy Number Loss ◽  
Next Generation ◽  
Generation Sequencing

e21709 Background: Molecular profiling of lung adenocarcinoma is essential for therapeutic decision-making and prognosis predicting. Pleural effusion may provide an opportunity for molecular profiling and thereby possibly provide information enabling targeted therapy. In this study, we performed next generation sequencing (NGS) in pleural effusion samples in order to study molecular profiling of lung adenocarcinoma using pleural effusion specimens. Methods: 45 Chinese lung adenocarcinoma patients with pleural effusion specimens were included. The pleural effusion samples were centrifugated, then cell pellets were collected and prepared into cell blocks. Genetic mutations were assessed using a validated targeted next generation sequencing assay. Immunohistochemistry (IHC) of PD-L1 was performed with 22C3 kit. Results: In 45 pleural effusion samples collected, 43 (95.5%) patients had at least one mutation classed as pathogenic or likely pathogenic. There were 245 somatic mutation and 160 germline mutations were detected, with an average of 8.0 mutations per patient. Of the 45 specimens with somatic mutations, seventeen (37.8%) of harbored EGFR mutations. The most frequent mutations were the deletion mutation in exon19 (15/17, 40.9%), the point mutation (L858R) in exon 21 (13/17, 76.5%), and resistance mutation (T790M) in exon 20(4/17,23.5%). Aside from the EGFR mutation, 1 case exhibited KRAS mutation (G12C), 1 case harbored ERBB2 mutation(Y772_A775dup),1 case harbored TP53 mutation, and 2 cases exhibited fusion (EML4-ALK, KIF5B-RET). 2 cases exhibited CD274 copy number gain, 2 cases exhibited CDK4 copy number gains, and one case carried CDK6 copy number gain, one case carried CKD6 copy number loss. The top frequent germline mutation genes were APC (5/45), ALK (4/45), ARID1A (4/45) and BARD1 (4/45). Regarding biomarkers for immunotherapy, three sample showed TMB-H (6.7%), and one sample showed MSI-H (2.2%). Of 29 samples underwent PDL1 IHC test, 21 samples (72.4%) show positive PDL1 expression, in concordance with previous reported rates. Conclusions: These results suggest that pleural effusions are important specimens for oncogene mutation analysis and enable targeted therapy for patients with lung adenocarcinoma.

CSF rhinorrhea following alectinib treatment for anaplastic lymphoma kinase rearranged lung adenocarcinoma - e contrario

2020 ◽  
Vol 5 ◽  
pp. 127-130
Author(s):  
Deepa Shrestha ◽  
Raghava Rao Gandra ◽  
Ramandeep Singh Virk ◽  
Paramjeet Singh ◽  
Aditi Mehta ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Skull Base ◽  
Anaplastic Lymphoma Kinase ◽  
Trauma Surgery ◽  
Skull Base Tumors ◽  
Alk Rearrangement ◽  
Csf Rhinorrhea ◽  
Anaplastic Lymphoma ◽  
Metastatic Lung

Cerebrospinal fluid (CSF) rhinorrhea is a condition characterized by leakage of CSF from skull base through the nostril(s). It is commonly associated with trauma, surgery, infections of paranasal sinuses/skull base, and intracranial and skull base tumors. Among malignant causes, lung cancer is rarely associated with CSF rhinorrhea. Herein, we report the case of a 51-year-old lady who was initially diagnosed with metastatic lung adenocarcinoma (LUAC) with anaplastic lymphoma kinase (ALK) rearrangement and initiated on treatment with alectinib. She had good clinicoradiological response, but on follow-up developed CSF rhinorrhea that required surgical correction. We also discuss the proposed mechanisms associated with occurrence of CSF rhinorrhea in the setting of metastatic ALK-rearranged LUAC.

scholarly journals Anaplastic Lymphoma Kinase Immunocytochemistry on Cell-Transferred Cytologic Smears of Lung Adenocarcinoma

2015 ◽  
Vol 59 (2) ◽  
pp. 213-218 ◽  
Author(s):  
Chen Zhang ◽  
Melissa L. Randolph ◽  
Kelly J. Jones ◽  
Harvey M. Cramer ◽  
Liang Cheng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Anaplastic Lymphoma Kinase ◽  
Needle Aspiration ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma ◽  
Ct Technique ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Hybridization In Situ

Background: Anaplastic lymphoma kinase (ALK) immunohistochemical staining on formalin-fixed paraffin-embedded tissue or cell blocks (CB) has been reported as an effective alternative to fluorescence hybridization in situ (FISH) for the detection of ALK gene rearrangement. However, CB frequently lack adequate cellularity even when the direct smears are cellular. This study aims to assess the utility of ALK immunocytochemical (ICC) staining on direct smears using the cell transfer (CT) technique for the detection of ALK rearrangement. Methods: Fine-needle aspiration (FNA) cases of lung adenocarcinoma in which the ALK status had been determined by FISH on CB or a concurrent biopsy were identified. ICC staining for ALK was performed on alcohol-fixed Papanicolaou-stained direct smears using the CT technique. ALK immunoreactivity was evaluated using a modified semiquantitative scale. Results were compared with those of FISH. Results: A total of 47 FNA specimens were included. Five of 7 FISH-positive cases showed positive ALK ICC staining (71.4%), and 39 of 40 FISH-negative cases were negative on ALK ICC staining (97.5%). The overall correlation between ALK ICC and FISH was 93.6%. Conclusion: ICC performed on FNA smears using the CT technique is an alternative method for the assessment of ALK rearrangement, especially when CB lack adequate cellularity.

scholarly journals Discordance between Fluorescence In Situ Hybridization and Immunohistochemistry Analysis of Anaplastic Lymphoma Kinase Rearrangement in Indian Patients with Non-Small Cell Lung Cancer

2020 ◽  
Vol 9 (02) ◽  
pp. 109-114
Author(s):  
Manish Kumar ◽  
Kishore Kumar ◽  
Harinder Pal Singh ◽  
Suresh Nair ◽  
Amol Patel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Pleural Effusion ◽  
Brain Metastasis ◽  
Fluorescence In Situ Hybridization ◽  
Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma

Abstract Aims This study aims to evaluate the incidence of anaplastic lymphoma kinase (ALK) mutation in nonsmall cell lung cancer (NSCLC) incorporating fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods and to look for any discordance. Methods We evaluated 101 samples obtained from an enriched cohort of NSCLCs patients from the Army Hospital Research and Referral, New Delhi, India, between November 2016 and November 2018. IHC was performed using the highly-sensitive D5F3 rabbit monoclonal primary antibody. FISH was performed with dual-color, break-apart probe (ZytoLight SPEC) on formalin-fixed, and paraffin-embedded tissue. Discordance between IHC and FISH for ALK rearrangements was evaluated. Pearson correlation coefficient (r) was performed to identify any association of ALK presence (by IHC and FISH) with smoking brain metastasis, programmed death-ligand (PD-L1) expression, pleural effusion, and histopathological subtype. Results A total of 7.92% (8/101) cases tested by IHC and 9.9% (10/101) cases tested by FISH were positive for ALK rearrangement. Of 93 ALK IHC-negative cases, 4 were ALK FISH-positive, whereas of 91 ALK FISH-negative cases, 4 were ALK IHC-positive cases. The correlation analysis demonstrated no or very weak correlation in ALK mutations by IHC or FISH with smoking, brain metastasis, PD-L1 expression, pleural effusion, and histopathological examination, except a weak positive correlation (r = 0.33) observed between brain metastasis and ALK rearrangement identified by FISH. Conclusions Our study demonstrated a somewhat similar incidence of ALK FISH-positive cases and ALK IHC-positive cases, though the incidence was numerically higher for ALK-FISH method.

scholarly journals EML4-ALK positive lung adenocarcinoma with skeletal muscle metastasis in the right calf which was treatable with lorlatinib after resistance to treatment with alectinib

2021 ◽  
Vol 14 (4) ◽  
pp. e240295
Author(s):  
Hironari Matsuda ◽  
Munechika Hara ◽  
Shin-Ichiro Iwakami ◽  
Kazuhisa Takahashi
Keyword(s):  
Skeletal Muscle ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Stable Condition ◽  
Japanese Woman ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma ◽  
Resistance To Treatment ◽  
Alk Positive ◽  
The Right

This report concerns a patient with skeletal muscle metastases due to lung adenocarcinoma harbouring an echinoderm microtubule-associated protein-like-4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement, who was successfully treated with lorlatinib after resistance to alectinib. A right lower lobectomy based on a diagnosis of lung adenocarcinoma was performed on a 77-year-old Japanese woman. After 7 months of surgical resection, a mass in the right calf was observed. A fine-needle aspiration biopsy from the mass was performed and the mass was diagnosed as metastatic adenocarcinoma harbouring EML4-ALK rearrangement. Alectinib was administered for 10 months. Then, administration of lorlatinib, an ALK tyrosine kinase inhibitor classified as third generation, was initiated after resistance to treatment with alectinib. After starting treatment with lorlatinib, the gastrocnemius tumour diminished and has maintained a stable condition. Our case suggests that EML4-ALK positive lung adenocarcinoma is treatable with lorlatinib after resistance to treatment with alectinib.

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