Molecular characteristics of low-grade serous carcinoma in effusions.

Abstract

The molecular characteristics of low-grade serous carcinoma (LGSC) in serous effusions have not been studied previously. The present study analysed the molecular profile of LGSC at this anatomical site. Specimens consisted of a series of 17 serous effusions (15 peritoneal, 2 pleural) from 16 patients, of which 15 were LGSC and 2 serous borderline tumour (SBT) who later progressed to LGSC. For comparative purposes, 9 surgical specimens from 6 patients with LGSC were analysed. Fresh-frozen cell pellets and surgical specimens underwent targeted next-generation sequencing covering 50 unique genes. Mutations were found in tumours from 14 of the 22 patients, of whom 4 had 2 different mutations and 10 had a single mutation. Overall, the most common mutations were in KRAS (n= 3) and BRAF (n= 3), followed by NRAS (n= 2), CDK2NA (n= 2), TP53 (n= 2), ATM (n= 2). Mutations in MET, STK11, ERBB2 and FLT3 were found in one case each. Patient-matched specimens had the same molecular profile. Both effusions with TP53 mutation had concomitant ATM mutation, and both stained immunohistochemically with a wild-type pattern. The absence of mutations was associated with a trend for shorter overall survival in univariate analysis (p= 0.072). The molecular alterations in LGSCs in serous effusions are consistent with those found in solid tumours, with frequent alterations in the mitogen-activated protein kinase pathway. Mutations in LGSC may be a marker of better outcomes.