FGFR2 Alterations in Endometrial Carcinoma.
Sonia Gatius, Ainara Azueta, Ana Velasco, Maria Santacana, Judit Pallares, Xavier Matias-Guiu. Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Spain
Background: Fibroblast growth factor receptor 2 (FGFR2) is a tyrosine kinase receptor involved in many biological processes such as embryogenesis, adult tissue homeostasis and cell proliferation. Mutations in FGFR2 have been reported in up to 16% of endometrial carcinomas (EC) identical to those found in congenital craniofacial disorders. Inhibition of FGFR2 could be a new therapeutic target in EC.
Design: FGFR2 immunostaining was assessed in three tissue microarrays (TMA): one constructed from paraffin-embedded blocks of 70 samples of normal endometrium (NE) in different phases of menstrual cycle, and two TMAs containing EC samples (95 and 62 cases). FGFR2 expression was correlated with stage, histological type and grade as well as with immunostaining of PTEN, RASSF1A, estrogen and progesterone receptors and KI67. FGFR2 mutations were assessed by PCR and direct sequencing, with DNA obtained from 31 paraffin-embedded EC samples and corresponding normal tissues.
Results: In NE, FGFR2 expression was higher in the secretory than in the proliferative phase (p=0,001). Cytoplasmic expression of FGFR2 was higher in EC when compared with NE (p=0, 0283), particularly when comparing NE with endometrioid carcinomas (EEC). Interestingly, nuclear staining was observed in some cases, and it was less frequent in EC when compared with NE (p=0, 0465). There were no statistical differences when comparing superficial and myoinvasive tumor samples. EEC showed higher expression of FGFR2 than non-endometrioid carcinomas, but the difference lacked statistical significance. Grade III EEC showed decreased FGFR2 expression when compared with grade II EEC (p=0,009). No differences were found regarding pathological stage. Two missense mutations of FGFR2 gene were detected in exons 6 and 11 (S252W and N540K respectively), each of them in EEC (6.45%). None of the remaining 29 cases exhibited any mutation.
Conclusions: FGFR2 cytoplasmic expression is higher in EC in comparison with NE, which support a role of FGFR2 as oncogene in EC, and suggests that FGFR2 could be a possible therapeutic target in EC. However, the frequency of mutated cases in this series seems to be lower than in other previous series.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Monday, February 28, 2011 1:00 PM
Poster Session II # 246, Monday Afternoon