Prognostic value of ALK overexpression and molecular abnormalities in high-grade serous ovarian carcinoma

Article type: Research Article

Authors: Gorczyński, Adam^{a; *} | Miszewski, Kevin^b | Gager, Yann^c | Koch, Sonja^d | Pötschke, Jane^d | Ugrinovski, Dimitar^d | Gabert, Jörg^d | Pospieszyńska, Agata^e | Wydra, Dariusz^e | Duchnowska, Renata^f | Szymanowski, Bartosz^f | Cierniak, Szczepan^g | Kruecken, Irene^{d; h} | Neumann, Karstenⁱ | Mirkov, Katarinaⁱ | Biernat, Wojciech^a | Czapiewski, Piotrⁱ

Affiliations: [a] Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland | [b] Department of Urology, Medical University of Gdansk, Gdansk, Poland | [c] ParoX GmbH, Leipzig, Germany | [d] PathoNext GmbH, Leipzig, Germany | [e] Department of Gynecology, Obstetrics and Neonatology, Medical University of Gdansk, Gdansk, Poland | [f] Department of Oncology, Military Institute of Medicine, National Research Institute, Warsaw, Poland | [g] Department of Pathology, Military Institute of Medicine, National Research Institute, Warsaw, Warsaw, Poland | [h] Institute of Pathology, University of Leipzig, Leipzig, Germany | [i] Institute of Pathology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane, Dessau, Germany

Correspondence: [*] Corresponding author: Adam Gorczyński, Department of Pathomorphology, Medical University of Gdansk, Mariana Smoluchowskiego 17, 80-214 Gdansk, Poland. Tel.: + 48 698480519; E-mail: adam.gorczynski@gumed.edu.pl.

Abstract: BACKGROUND: ALK receptor tyrosine kinase (ALK) aberrations have an established role in pathogenesis of many neoplasms, but their clinical significance in high grade serous ovarian carcinoma (HGSOC) is unclear. OBJECTIVE: To analyse the frequency of ALK overexpression, molecular abnormalities of ALK, and their impact on the progression-free survival (PFS) and overall survival (OS) in HGSOC. METHODS: Protein expression was examined by immunohistochemistry (IHC) using three different clones of anti-ALK antibody. The presence of translocations was analysed using fluorescent in situ hybridization. Next-generation sequencing was used for studying the copy number variation, as well as point mutation and translocations involving other commonly rearranged genes. RESULTS: ALK overexpression was demonstrated in up to 52% of tumours, whereas ALK copy gains in 8.2%, with no clear impact on survival. ALK point mutations were identified in 13 tumours (8.9%), with 3 belonging to the class IV showing significantly better OS. A trend suggesting better PFS was also noticed in these cases. Additionally, three gene fusions were found: ERBB2-GRB7, PRKCA-BRCA1 and SND1-BRAF, none of which has been previously described in HGSOC. CONCLUSIONS: HGSOC harbouring activating ALK mutations might be associated with a better survival, while ALK overexpression and ALK amplification does not impact the prognosis.

Keywords: BRCA1, BRAF, ERBB2, fusion, point mutations

DOI: 10.3233/CBM-230117

Journal: Cancer Biomarkers, vol. 38, no. 1, pp. 17-26, 2023