Document Detail

FGFR2 alterations in endometrial carcinoma.
MedLine Citation:
PMID:  21725289     Owner:  NLM     Status:  MEDLINE    
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 10-12% of endometrial carcinomas identical to those found in congenital craniofacial disorders. Inhibition of FGFR2 could be a new therapeutic target in endometrial carcinoma. FGFR2 immunostaining was assessed in three tissue microarrays: one constructed from paraffin-embedded blocks of 60 samples of normal endometrium in different phases of menstrual cycle, and two tissue microarrays containing endometrial carcinoma 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, KI67, Cyclin D1, STAT-3 and SPRY2. FGFR2 mutations were assessed by PCR and direct sequencing, with DNA obtained from 31 paraffin-embedded endometrial carcinoma samples. In normal endometrium, FGFR2 expression was higher in the secretory than in the proliferative phase (P=0.001), with an inverse correlation with Ki67 (P=0.00032), suggesting a tumor-suppressor role for FGFR2 in normal endometrium. Cytoplasmic expression of FGFR2 was higher in endometrial carcinoma when compared with the atrophic endometrium from the same patients (P=0.0283), but was lower in comparison with normal endometrium from women in the menstrual cycle. Interestingly, nuclear staining was observed in some cases, and it was less frequent in endometrial carcinoma when compared with the adjacent atrophic endometrium (P=0.0465). There were no statistical differences when comparing superficial and myoinvasive endometrial carcinoma samples. Endometrioid endometrial carcinomas showed higher expression of FGFR2 than nonendometrioid endometrial carcinomas (fold change 2.56; P=0.0015). Grade III endometrioid endometrial carcinomas showed decreased FGFR2 expression when compared with grade II endometrioid endometrial carcinomas (P=0.0055). No differences were found regarding pathological stage. Two missense mutations of FGFR2 gene were detected in exons 6 and 11 (S252W and N549K, respectively; 6.45%). Results support the hypothesis that FGFR2 has a dual role in the endometrium, by inhibiting cell proliferation in normal endometrium during the menstrual cycle, but acting as an oncogene in endometrial carcinoma.
Sonia Gatius; Ana Velasco; Ainara Azueta; Maria Santacana; Judit Pallares; Joan Valls; Xavier Dolcet; Jaime Prat; Xavier Matias-Guiu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-01
Journal Detail:
Title:  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc     Volume:  24     ISSN:  1530-0285     ISO Abbreviation:  Mod. Pathol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-03     Completed Date:  2012-02-28     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  8806605     Medline TA:  Mod Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1500-10     Citation Subset:  IM    
Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.
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MeSH Terms
Carcinoma / chemistry*,  genetics,  pathology
Cell Proliferation
Cyclin D1 / analysis
DNA Mutational Analysis
Endometrial Neoplasms / chemistry*,  genetics,  pathology
Endometrium / chemistry*,  pathology
Intracellular Signaling Peptides and Proteins / analysis
Ki-67 Antigen / analysis
Menstrual Cycle
Mutation, Missense
Neoplasm Staging
PTEN Phosphohydrolase / analysis
Polymerase Chain Reaction
Receptor, Fibroblast Growth Factor, Type 2 / analysis*,  genetics
Receptors, Estrogen / analysis
Receptors, Progesterone / analysis
STAT3 Transcription Factor / analysis
Tissue Array Analysis
Tumor Markers, Biological / analysis*,  genetics
Tumor Suppressor Proteins / analysis
Reg. No./Substance:
0/CCND1 protein, human; 0/Intracellular Signaling Peptides and Proteins; 0/Ki-67 Antigen; 0/RASSF1 protein, human; 0/Receptors, Estrogen; 0/Receptors, Progesterone; 0/SPRY2 protein, human; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Tumor Markers, Biological; 0/Tumor Suppressor Proteins; 136601-57-5/Cyclin D1; EC protein, human; EC, Fibroblast Growth Factor, Type 2; EC protein, human; EC Phosphohydrolase

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