FGFR2 alterations in endometrial carcinoma

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 congenit...

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Authors: Gatius, S, Velasco, A, Azueta, A, Santacana, M, Pallares, J, Valls, J, Dolcet, X, Prat, J, Matias-Guiu, X
Format: article
Status:Published version
Publication Date:2011
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p11659
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11659
Access Level:Open access
Keyword:endometrial carcinoma
FGFR2
mutation
oncogene
tissue microarray
tumor-suppressor gene
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spelling FGFR2 alterations in endometrial carcinomaGatius, SVelasco, AAzueta, ASantacana, MPallares, JValls, JDolcet, XPrat, JMatias-Guiu, Xendometrial carcinomaFGFR2mutationoncogenetissue microarraytumor-suppressor geneFibroblast 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. Modern Pathology (2011) 24, 1500-1510; doi:10.1038/modpathol.2011.110; published online 1 July 2011SPRINGERNATURE2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11659MODERN PATHOLOGYISSN: 08933952ISSNe: 15300285reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p116592026-06-14T12:41:47Z
dc.title.none.fl_str_mv FGFR2 alterations in endometrial carcinoma
title FGFR2 alterations in endometrial carcinoma
spellingShingle FGFR2 alterations in endometrial carcinoma
Gatius, S
endometrial carcinoma
FGFR2
mutation
oncogene
tissue microarray
tumor-suppressor gene
title_short FGFR2 alterations in endometrial carcinoma
title_full FGFR2 alterations in endometrial carcinoma
title_fullStr FGFR2 alterations in endometrial carcinoma
title_full_unstemmed FGFR2 alterations in endometrial carcinoma
title_sort FGFR2 alterations in endometrial carcinoma
dc.creator.none.fl_str_mv Gatius, S
Velasco, A
Azueta, A
Santacana, M
Pallares, J
Valls, J
Dolcet, X
Prat, J
Matias-Guiu, X
author Gatius, S
author_facet Gatius, S
Velasco, A
Azueta, A
Santacana, M
Pallares, J
Valls, J
Dolcet, X
Prat, J
Matias-Guiu, X
author_role author
author2 Velasco, A
Azueta, A
Santacana, M
Pallares, J
Valls, J
Dolcet, X
Prat, J
Matias-Guiu, X
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv endometrial carcinoma
FGFR2
mutation
oncogene
tissue microarray
tumor-suppressor gene
topic endometrial carcinoma
FGFR2
mutation
oncogene
tissue microarray
tumor-suppressor gene
description 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. Modern Pathology (2011) 24, 1500-1510; doi:10.1038/modpathol.2011.110; published online 1 July 2011
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11659
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11659
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv SPRINGERNATURE
publisher.none.fl_str_mv SPRINGERNATURE
dc.source.none.fl_str_mv MODERN PATHOLOGY
ISSN: 08933952
ISSNe: 15300285
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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