Cytology material is equivalent to tumor tissue in determining mutations of BRCA 1/2 genes in patients with tubo-ovarian high grade serous carcinoma

Abstract

Background High-grade serous ovarian cancer is a detrimental disease. Treatment options in patients with a recurrent disease are dependent on BRCA1/2 mutation status since only patients with known BRCA mutation are eligible for treatment with poly(ADP-ribose) polymerase inhibitors (PARPi). The aim of this study was to compare concordance of BRCA mutation analyses from cytological samples (CS) with BRCA mutation analyses from histological formalin fixed paraffin embedded (FFPE) samples. Methods Mutation analysis of BRCA1 and BRCA2 genes was performed in 44 women diagnosed with primary or recurrent high-grade ovarian cancer from three different samples: blood, cytological sample (ascites, pleural effusion and enlarged lymph nodes) and tumor tissue. Results from all three samples were compared. Results Among 44 patients, there were 15 germline mutations and two somatic mutations. A 100% concordance was found between cytological and histologic samples. Conclusion There is a 100% concordance in BRCA mutation testing between cytological and histologic samples. BRCA mutation testing from CS could replace testing from FFPE tissue in clinical decision making in ovarian cancer patients. Trial registration The study was retrospectively registered at ISRCTN registry on 24/11/2015 - ISRCTN42408038 .

Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

“…The possible reason for the lower rate of gBRCA and sBRCA mutations in our results with respect to other studies [14,24,27,28] might be that we were limited to the population of Portsmouth, UK. Possibly, in this population, the BRCA1/2 mutations are less prevalent, compared to the populations described in other studies.…”

“…The rate of g BRCA PVs has been reported in the range of 8–34% in different studies. The Cancer Genome Atlas Research Network found mutations in 22% of a series of 489 cases [ 23 ], while Gornjec et al found mutations in 34% of a relatively small series of 44 patients [ 24 ]. In our series, the rate of germline mutations was 10.4%, which is comparable to the figure of 7.8% reported by Plaskocinska et al in an East Anglia region study of 232 cases [ 25 ].…”

Year 1: Experiences of a tertiary cancer centre following implementation of reflex BRCA1 and BRCA2 tumor testing for all high-grade serous ovarian cancers in a universal healthcare system

“…This is particularly important for HGSOC patients as 51% (89/174) patients in the total study cohort were treated with neoadjuvant chemotherapy. Emerging tests validated on cytology samples may provide an alternative to tumor testing, as these samples are easier to collect and 100% concordance of BRCA1/2 results has been reported between tumor and cytology samples [31,32]. This would provide opportunities to initiate tumor testing earlier in the patient journey, particularly for those treated with neoadjuvant chemotherapy.…”

Next-generation sequencing-based BRCA testing on cytological specimens from ovarian cancer ascites reveals high concordance with tumour tissue analysis

“…However, so far, few studies analysed BRCA1/2 status on malignant cells recovered from peritoneal/pleural fluids 15 16. Recently, Barquín et al reported on the feasibility of BRCA1/2 mutation analysis on 10 cytological samples from fresh peritoneal washings17 and Gornjec et al evaluated a large cohort of patients with ovarian cancer using capture-based NGS approaches 18. However, they assumed that fresh peritoneal liquid was available immediately for DNA extraction17 or used as a protocol for cytological specimen preparation including a cell medium addition step that is not routinely performed in most diagnostic laboratories 18.…”

“…Recently, Barquín et al reported on the feasibility of BRCA1/2 mutation analysis on 10 cytological samples from fresh peritoneal washings17 and Gornjec et al evaluated a large cohort of patients with ovarian cancer using capture-based NGS approaches 18. However, they assumed that fresh peritoneal liquid was available immediately for DNA extraction17 or used as a protocol for cytological specimen preparation including a cell medium addition step that is not routinely performed in most diagnostic laboratories 18. In the last years, our group demonstrated that archival smear slides may represent suitable samples for molecular tests, including NGS analysis 19 20.…”