Fibroblast growth factor receptor 2 (FGFR2) amplification and polysomy in serous ovarian cancer

Date

08 Oct 2016

Session

Poster Display

Presenters

Alexandra Tyulyandina

Citation

Annals of Oncology (2016) 27 (6): 296-312. 10.1093/annonc/mdw374

Authors

A. Tyulyandina1, I. Demidova2, M. Gikalo2, I. Tsimafeyeu3, S. Tjulandin1

Author affiliations

  • 1 Clinical Pharmacology And Chemotherapy, N. N. Blokhin Russian Cancer Research Center, 115478 - Moscow/RU
  • 2 Molecular Genetics, Moscow City Oncology Hospital No. 62, 143423 - Moscow/RU
  • 3 Russco, Russian Society of Clinical Oncology, 127051 - Moscow/RU
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Background

In recent studies the overexpression of FGFR2 was detected in 95% of clear cell ovarian carcinomas. FGFR2 aberrations were detected in 9% of ovarian cancers. Up to date there is no data about FGFR2 amplification and its predictive role in ovarian cancer patients.

Methods

78 paraffin-embedded samples from 33 patients with stage III-IV serous adenocarcinoma of ovary were analyzed by fluorescence in situ hybridization (FISH) to identify FGFR2 amplification and level of polysomy. All patients received primary and secondary cytoreduction for recurrence and standard chemotherapy. Scoring for amplification and polysomy level was adopted from previous studies for gastric cancer [Su et al. BJC 2014]. Material from each patient included 3 samples: from primary ovarian tumor, from primary metastatic lesions, and from relapse lesions. The analysis was performed in all three samples regardless of the presence of FGFR2 amplification or heterogeneity in primary tumor.

Results

Amplification of FGFR2 was detected in 5 patients (15.1%). High-level polysomy (HLP) was observed in 16 patients (48.5%). Intratumoral heterogeneity was detected in 13 of 21 (61.9%) patients with FGFR2 abnormalities in all three samples. Interestingly, FGFR2 amplification/HLP were observed in 55.5% (10 of 18 samples) of metastatic lesions after primary surgery and in 67.8% (19 of 28) of relapsed tumors, but only in 26.1% (6 of 23) of primary tumors. Median progression-free survival (PFS) after first line platinum-based chemotherapy was 6.3 months in patients with amplification and 17.2 months in patients without amplification (p = 0.05). Median interval between the end of first line therapy and progression after second line therapy (PFS2) was 18.7 and 59.5 months in patients with and without amplification, respectively (p = 0.005). HLP did not correlate with PFS (P = 0.11) and PFS2 (p = 0.45). Overall survival data is still premature.

Conclusions

For the first time we described amplification and HLP of FGFR2 in 63.6% of patients with serous ovarian cancer. Most of these patients had intratumoral heterogeneity. FGFR2 amplification could significantly impact on long-term outcomes.

Clinical trial identification

Legal entity responsible for the study

RUSSCO

Funding

RUSSCO

Disclosure

All authors have declared no conflicts of interest.

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