scholarly journals Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma

2020 ◽  
Vol 21 (24) ◽  
pp. 9705
Author(s):  
Takahiro Tashiro ◽  
Kosuke Imamura ◽  
Yusuke Tomita ◽  
Daisuke Tamanoi ◽  
Akira Takaki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Driver Mutations ◽  
Single Individual ◽  
Alk Rearrangement ◽  
Metastatic Tumors ◽  
Anaplastic Lymphoma ◽  
Metastatic Lesions

Evolution of tumor-immune microenviroments (TIMEs) occurs during tumor growth and dissemination. Understanding inter-site tumor-immune heterogeneity is essential to harness the immune system for cancer therapy. While the development of immunotherapy against lung cancer with driver mutations and neuroendocrine tumors is ongoing, little is known about the TIME of large cell neuroendocrine carcinoma (LCNEC) or anaplastic lymphoma kinase (ALK) rearrangement-positive lung cancer. We present a case study of a 32-year-old female patient with ALK-rearrangement-positive LCNEC, who had multiple distant metastases including mediastinal lymph-node, bilateral breasts, multiple bones, liver and brain. Multiple biopsy samples obtained from primary lung and three metastatic tumors were analyzed by fluorescent multiplex immunohistochemistry. Tissue localizations of tumor-infiltrating lymphocytes in the tumor nest and surrounding stroma were evaluated. T cell and B cell infiltrations were decreased with distance from primary lung lesion. Although each tumor displayed a unique TIME, all tumors exhibited concomitant regression after treatment with an ALK-inhibitor. This study provides the first evidence of the coexistence of distinct TIME within a single individual with ALK-rearrangement-positive LCNEC. The present study contributes to our understanding of heterogeneous TIMEs between primary and metastatic lesions and provides new insights into the complex interplay between host-immunity and cancer cells in primary and metastatic lesions.

scholarly journals Large Cell Neuroendocrine Carcinoma Harboring an Anaplastic Lymphoma Kinase (ALK) Rearrangement with Response to Alectinib

2018 ◽  
Vol 57 (5) ◽  
pp. 713-716 ◽  
Author(s):  
Nobuyoshi Hayashi ◽  
Akihisa Fujita ◽  
Toyohiro Saikai ◽  
Hirotugu Takabatake ◽  
Mie Sotoshiro ◽  
...  
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Anaplastic Lymphoma Kinase ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma

Metastatic large cell neuroendocrine carcinoma of the lung arising from the uterus: A pitfall in lung cancer diagnosis

2016 ◽  
Vol 212 (7) ◽  
pp. 654-657 ◽  
Author(s):  
Kyoko Ono ◽  
Naho Ruiz Yokota ◽  
Emi Yoshioka ◽  
Akira Noguchi ◽  
Kota Washimi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Neuroendocrine Carcinoma ◽  
Cancer Diagnosis ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Lung Cancer Diagnosis

scholarly journals ALK Mutation Status in EGFR-negative Non-small-cell Lung Cancer Patients in Bulgaria

Folia Medica ◽  
2018 ◽  
Vol 60 (3) ◽  
pp. 397-401
Author(s):  
Slaveyko N. Djambazov ◽  
Toni Y. Vekov ◽  
Evgeni V. Mekov ◽  
Georgi S. Slavchev ◽  
Rosen E. Petkov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Anaplastic Lymphoma ◽  
Nsclc Patients

Abstract Background: Patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement mutation are found to be 3–13%. Aim: To evaluate the prevalence of ALK mutations in EGFR-negative NSCLC patients in Bulgaria. Materials and methods: One hundred and thirty-two patients with EGFR-negative NSCLC were examined for ALK mutation analysis between January and June 2016. Data were obtained from patients’ register of four major oncological hospitals in Bulgaria. Results: Data were available for 124 (93.9%) patients, tumor mass was insufficient for analysis in 8 (6.1%) patients. Most of the patients were with adenocarcinoma (82 patients, 62.1%); 11 patients (8.3%) were with squamous histology and 2 patients (1.5%) were with other type of NSCLC. Histology data were missing in 37 patients (28.0%). ALK mutation was confirmed in 5 patients (3.8%), 119 (90.2%) patients had ALK wild type. ALK positive patients were with adenocarcinoma (n=3), squamous cell carcinoma (n=1) and other type (n=1) NSCLC. All ALK mutations were observed in never smokers (n=3) and former smokers (n=2). Conclusion: The present study is the first of this kind in Bulgaria – it investigates the prevalence of ALK mutation rate in EGFR-negative NSCLC patients, which was found to be 3.8%. The presence of EGFR, ALK or other driver mutations is a prerequisite for targeted therapy and thus needs to be accurately assessed in NSCLC.

scholarly journals Fluorescence in Situ Hybridization (FISH) for Detecting Anaplastic Lymphoma Kinase (ALK) Rearrangement in Lung Cancer: Clinically Relevant Technical Aspects

2019 ◽  
Vol 20 (16) ◽  
pp. 3939 ◽  
Author(s):  
Zhenya Tang ◽  
Lu Wang ◽  
Guilin Tang ◽  
L. Jeffrey Medeiros
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Simultaneous Detection ◽  
The United States ◽  
Driver Mutations ◽  
Alk Rearrangement ◽  
Technical Aspects ◽  
Anaplastic Lymphoma

In 2011, the Vysis Break Apart ALK fluorescence in situ hybridization (FISH) assay was approved by the United States Food and Drug Administration as a companion diagnostic for detecting ALK rearrangement in lung cancer patients who may benefit from treatment of tyrosine kinase inhibitor therapy. This assay is the current “gold standard”. According to updated ALK testing guidelines from the College of American Pathologists, the International Association for the Study of Lung Cancer and the Association for Molecular Pathology published in 2018, ALK immunohistochemistry is formally an alternative to ALK FISH, and simultaneous detection of multiple hot spots, including, at least, ALK, ROS1, RET, MET, ERBB2, BRAF and KRAS genes is also recommended while performing next generation sequencing (NGS)-based testing. Therefore, ALK status in a specimen can be tested by different methods and platforms, even in the same institution or laboratory. In this review, we discuss several clinically relevant technical aspects of ALK FISH, including pros and cons of the unique two-step (50- to 100-cell) analysis approach employed in the Vysis Break Apart ALK FISH assay, including: the preset cutoff value of ≥15% for a positive result; technical aspects and biology of discordant results obtained by different methods; and incidental findings, such as ALK copy number gain or amplification and co-existent driver mutations. These issues have practical implications for ALK testing in the clinical laboratory following the updated guidelines.

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