abstract
Highlights
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- One-third of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) have low percentage of neoplastic nuclei (PNN < 70%).
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- Higher PNN is associated with suboptimal cytoreduction and lower PNN is associated with inherited BRCA2 mutations.
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- Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.
Objective
Most
molecular analyses of high-grade serous ovarian, peritoneal and
fallopian tube carcinomas (HGSC) require ≥ 70% tumor (neoplastic) cell
nuclei. We characterized the distribution of the percentage of
neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN
with clinical outcomes to determine the fraction of cases outside this
range and whether this cut-off introduces selection bias.
Methods
Subjects
were prospectively enrolled and normal and neoplastic tissues were
snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received
neoadjuvant chemotherapy were excluded. PNN was determined by estimating
the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a
representative hematoxylin and eosin stained frozen section from the
primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing.
Results
PNN was < 70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P = 0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P = 0.018).
Overall survival was not significantly different between subjects with
< 70% or ≥ 70% PNN (median survival 51.8 vs. 46.6 months, P = 0.858).
Conclusions
One-third
of HGSC has PNN < 70%. Higher PNN is associated with suboptimal
cytoreduction, while lower PNN is associated with inherited BRCA2
mutations. Our findings suggest a nonrandom distribution of PNN that
may reflect cancer biology. Further studies exploring the stromal
microenvironment are needed. Molecular analyses of HGSC selected for
high PNN exclude a significant fraction of patients.