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

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.