Fap Alpha (Fibroblast Activation Protein-Alpha) Analysis In Breast Tumor Cells And Stroma After Neoadjuvant Treatment

CANCER RESEARCH(2017)

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摘要
Abstract Background: FAPα is a transmembrane serine protease expressed on cancer associated fibroblast that promotes tumour growth and invasion. In patients (pts) with poor outcome and survival FAPα is highly overexpressed. FAPα is also expressed in stroma across all breast cancer subtypes without association with clinicopathological factors. Pts without Complete Pathological Response (pCR) after Neoadjuvant Chemotherapy (NC) had poor outcome. We analysed the relationship between the expression of FAPα in stroma (fibroblast) and in epithelial breast cancer cells of pts without pCR after NC (taxanes, antracyclines and trastuzumab in Her2+). Methods: 60 pts were included. ER, PR and Ki67 were studied by IHQ (Ventana) and Her2 by FISH (PatnVysion). FAPα expression was determined by IHQ (polyclonal, Ventana). St Gallen guidelines for subtype of breast cancer were used. Results: 53 pts had tissue. Median age 47 years (range 29-68). Median tumour size 43mm and 10 (18.9%) were multifocal. 37 (69.8%) had positive axillary nodes. 47 were ductal invasive carcinomas. 33 (62.3%) were grade 2 and 20 (37.7%) grade 3. 44 pts (83%) had ER+ (20 luminal B), 17 (32%) Her2+ and 6 (11%) triple negative(TN). Median Ki67 was 22% (p25-75:15-38%). Miller-Payne response was 1.9% G1 (1pt), 43.4% G2 (23 pts), 41.5% G3 (22 pts) and 13.2% G4 (7 pts). The recurrences were 2 local and 12 distant (26.4%). Median FAPα in residual epithelial breast cancer cells after NC was 85% (p25-75:30-95%) and in the stroma 20% (p25-75:10-62%). Median epithelial FAPα was 55% in TN, 85% Her2, 72.5% luminal A and 92.5% in luminal B. Median stromal FAPα was 52.5% in TN, 20% Her2, 15% luminal A and 15% in luminal B. There is not association between stromal FAPα and clinicopathological features, but a higher epithelial FAPα was found in tumours wih higher ER, PR and Ki67. In luminal B subtype, stromal FAPα was smaller in pts with relapses (median 7.5%) than without relapses (median 30%). Conclusions: Stromal FAPα in residual cancer after NC is higher in TN breast cancer but without association with relapses in our small sample. However, in luminal B subtype stromal FAPα is smaller in pts with relapses. Citation Format: Calvo I, Prieto M, Suárez-Gauthier A, Pérez FJ, Hernández E, Acosta D, Cárdenas JM, López-Ríos F, Estévez LG. FAPα (fibroblast activation protein-α) analysis in breast tumor cells and stroma after neoadjuvant treatment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-16.
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breast tumor cells,fibroblast,fapα,tumor cells
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