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Prognostic value of ALK overexpression and molecular abnormalities in high-grade serous ovarian carcinoma
Adam Gorczyński1, Kevin Miszewski2, Yann Gager3
1Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.
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.
