A targeted expression panel for classification, gene fusion detection and PD-L1 measurements – Can molecular profiling replace immunohistochemistry in non-small cell lung cancer?

The histological classification of non-small-cell lung cancer (NSCLC) and identification of possible therapeutic targets are important for disease management. However, as biopsies are often small, with a limited amount of tumor cells, it can be challenging to obtain enough tissue for the needed number of diagnostic immunohistochemical stains and molecular analyses. In this study, we combined a small custom designed targeted expression panel with a commercial fusion transcript assay by which we were able to perform both a histological classification (transcribing the expression of the genes encoding TTF1, Napsin A, CK5/6, and the truncated P63 isoform ΔNp63 (p40) into either adenocarcinoma or squamous cell carcinoma) and an identification of fusion genes involving ALK, RET, and ROS1. The expression panel also included the PD-L1 encoding gene, CD274, in order to evaluate the PD-L1 mRNA potential for identification of patients who will benefit from immune checkpoint inhibitor treatment. We evaluated the panel using 42 NSCLC patient samples. The molecular profiling agreed with the original immunohistochemistry (IHC)-based classification in 93% of the cases. For ten of the patients, being fusion gene positive, the fusion transcripts were detected in 100%. The molecular assessment of PD-L1 also showed agreement with the original assessment made by IHC. In conclusion, this study presents a small, targeted expression panel with the potential to perform both a molecularly based histological classification and a fusion gene identification in NSCLC patients as well as identifying PD-L1 status from a very limited amount of starting material. READ ARTICLE

Experimental and Molecular Pathology DOI:10.1016/j.yexmp.2022.104749

Authors: Anita Tranberg Simonsen, Amalie Utke, Johanne Lade-Keller, Lasse Westphal Thomsen, Torben Steiniche, Magnus Stougaard

Case StudyKirk SmithApril 1, 2022RNA expression, NSCLC, NGS, Gene fusion, PD-L1

Identification of EML4-ALK fusion in a sporadic case of cholangiocarcinoma

•Patients with cholangiocarcinoma have extremely poor prognoses.
•No molecular targeted agents have been still approved for cholangiocarcinoma treatment.
•RNA sequencing disclosed the fusion transcript EML4-ALK in a patient with cholangiocarcinoma.
•Cholangiocarcinoma share some driver targetable mutations with other solid tumors. READ ARTICLE

European Journal of Internal Medicine DOI:10.1016/j.ejim.2019.10.030

Authors: Domenico Trombetta, Paola Parente, Tiziana Pia Latiano, Federico Pio Fabrizio, Lucia Anna Muscarella

EditorialKirk SmithNovember 9, 2019Cholangiocarcinoma, EML4-ALK, Gene fusion

Targeted next-generation sequencing revealed distinct clinicopathologic and molecular features of VCL-ALK RCC

Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a novel entity of rare tumors with only 10 cases reported in the literature. Three RCC cases bearing VCL-ALK gene fusion were all young African American patients and associated with sickle cell trait notably. In contrast to the 3 reported cases, this neoplasm occurred in a middle-age woman (57 years old) without any evidence of sickle cell trait and demonstrated an infiltrating growth pattern with tubular, tubulopapillary, and tubulocystic structures, overlapping with collecting duct carcinoma and renal medullary carcinoma. Abundant intraluminal mucin was also noted significantly in the histologic sections. Immunostaining showed strong membranous labeling for ALK protein. We applied a large panel-targeted next-generation sequencing to explore the molecular alterations in the current case, revealing a driver oncogene VCL-ALK gene fusion co-occurring with pathogenic mutations in EP300 and TRRAP genes. Thereafter, f..... READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2019.152651

Authors: Xiao-tong Wang, Ru Fang, Sheng-bing Ye, Ru-song Zhang, Rui Li, Xuan Wang, Rong-hao Ji, Zhen-feng Lu, Heng-hui Ma, Xiao-jun Zhou, Qiu-yuan Xia, Qiu Rao

Identification and Development of a Lung Adenocarcinoma PDX Model With STRN-ALK Fusion

Gene fusions involving the anaplastic lymphoma kinase gene (ALK) often leads to oncogenic activation of the ALK kinase resulting in tumor development in lung and other solid tumors. Accurate identification of the fusion gene in patients with lung cancer has profoundly impacted patients’ clinical performance and long-term survival. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2018.11.002

Authors: Hongzheng Ren, Xiaonan Hou, Patrick W. Eiken, Jin Zhang, Karlyn E. Pierson, Asha A. Nair, Jaime I. Davila, Helena Kovarikova, Jin Sung Jang, Sarah H. Johnson, Julian R. Molina, Randolph S. Marks, Ping Yang, Joanne E. Yi, Aaron S. Mansfield, Jin Jen