Molecular characteristics of low-grade serous carcinoma in effusions

Cytopathology. 2023 Mar;34(2):99-105. doi: 10.1111/cyt.13207. Epub 2023 Jan 23.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: effusion; low-grade serous carcinoma; survival; targeted sequencing.

MeSH terms

  • Cystadenocarcinoma, Serous* / diagnosis
  • Cystadenocarcinoma, Serous* / genetics
  • Cystadenoma, Serous* / pathology
  • Female
  • Humans
  • Mutation / genetics
  • Neoplasm Grading
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / genetics
  • Peritoneal Neoplasms*