Ovarian carcinomas (OC) often demonstrate rapid tumor shrinkage upon neoadjuvant chemotherapy (NACT). However, complete pathologic responses are very rare and the mechanisms underlying the emergence of residual tumor disease remain elusive. We hypothesized that the change of somatic BRCA1 status may contribute to this process. The loss-of-heterozygosity (LOH) at the BRCA1 locus was determined for 23 paired tumor samples obtained from BRCA1 germ-line mutation carriers before and after NACT. We observed a somatic loss of the wild-type BRCA1 allele in 74% (17/23) of OCs before NACT. However, a retention of the wild-type BRCA1 copy resulting in a reversion of LOH status was detected in 65% (11/17) of those patients after NACT. Furthermore, we tested 3 of these reversion samples for LOH at intragenic BRCA1 single nucleotide polymorphisms (SNPs) and confirmed a complete restoration of the SNP heterozygosity in all instances. The neoadjuvant chemotherapy for BRCA1-associated OC is accompanied by a rapid expansion of pre-existing BRCA1-proficient tumor clones suggesting that continuation of the same therapy after NACT and surgery may not be justified even in patients initially experiencing a rapid tumor regression.

The PIP analysis was very useful for understanding realistic expectations for the potential of BeHealthy and its inputs. As a result, we now plan to evaluate the impact of the program and, on this basis, further improve the program's implementation and dissemination to other locations.

PurposeAdipose tissue products may contribute to endometrial cancer (EC) initiation and further growth that encourages the analysis of this issue in patients with different obesity phenotypes.Methods/patientsOmental fat depot characteristics were studied in EC patients (n = 57) with “standard” (SO) or “metabolically healthy” (MHO) obesity. Collected omental samples were evaluated by immunohistochemistry /IHC/ for brown fat marker UCP1, CYP19 (aromatase) and macrophage infiltration markers (CD68, CD163, crown-like structures/CLS) expression. Total RNA extracted from the same samples was investigated for UCP1, CYP19, PTEN and adipokine omentin mRNA.ResultsImmunohistochemistry data revealed a statistically significant increase in aromatase and CD68 expression and tendency to increase of UCP1 expression in SO patients’ omental fat compared to samples obtained from MHO patients. Additionally, positive correlation of EC clinical stage with UCP1 protein and its mRNA content in omental fat was pronounced in MHO as well as SO group, while with omentin mRNA it was discovered only in patients with SO. An inclination to the correlation with better tumor differentiation was seen for UCP1 and CD68 protein expression in patients with MHO and with worse (high grade) differentiation—for CD68 expression in the group with SO.ConclusionsIn aggregate, this suggests that obesity phenotype has significant impact on omental fat tissue characteristics which is related to the clinical course of EC and may have practical consequences.

301 Background: FGFR2 status of a patient with metastatic gastric adenocarcinoma could be an important factor in determining optimal treatment strategy with FGFR2 inhibitors and antibodies. The question remains how well different assays agree on the FGFR2 status of the same patient and whether one test can be substituted by another. Methods: Pairwise comparison of 4 tests based on the same patient population was performed: 3 IHC assays [Abcam clone EPR24075-418, R&D clone 98706, Santa Cruz clone C-8] and one FISH test. One hundred and nine formalin-fixed, paraffin embedded samples (including 64 primary tumors and 45 metastases of same patients) were obtained and were stained with FGFR2 IHC assays. Two trained pathologists independently evaluated the percentages of tumor staining and their intensity. FGFR2 FISH was performed as described previously [Su, BJC 2014]. The concordance analysis was performed to assess (1) correlation of FGFR2 expression/amplification between different assays in primary and metastases, (2) the predictive properties of one test of another. Results: After evaluating the expression in the first 19 patients, further study was carried out only using the Abсam assay due to pronounced nuclear staining with other IHC tests. FGFR2 any level expression was detected in 29 (47%) primary tumors and 18 (40%) metastases with concordance of 91%. The prevalence of FGFR2 amplification was 9.4% and intratumoral heterogeneity was observed in 33% of FGFR2 amplified cases. Pearson Correlation Coefficients (PCC) were: 0.89, 0.38 and 0.35 between IHC3+/FISH, IHC≥1% stained cells/FISH and IHC≥10%/FISH, respectively. The table represents how well one assay can predict the same outcome (positivity or negativity) of another assay. Conclusions: Among patients who were negative by FISH, 86%-93% of the patients were negative by IHC assay (Abcam). Among patients who were positive by FISH, 75-80% of them were positive by IHC. FISH should not be recommended as a substitute for a FGFR2 IHC assay due to high probability of false negative prediction as a result of intratumoral heterogeneity and low PCC. [Table: see text]

No abstract