Premium
Inverse correlation of secreted frizzled‐related protein 4 and β‐catenin expression in endometrial stromal sarcomas
Author(s) -
Hrzenjak Andelko,
Tippl Michaela,
Kremser MarieLuise,
Strohmeier Bettina,
Guelly Christian,
Neumeister Doris,
Lax Sigurd,
Moinfar Farid,
Tabrizi Ali Dastranj,
IsadiMoud Narges,
Zatloukal Kurt,
Denk Helmut
Publication year - 2004
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1616
Subject(s) - biology , wnt signaling pathway , stromal cell , endometrial stromal sarcoma , in situ hybridization , complementary dna , suppression subtractive hybridization , frizzled , cdna library , immunohistochemistry , cancer research , microbiology and biotechnology , pathology , gene , gene expression , genetics , immunology , medicine
Endometrial stromal sarcomas are rare uterine tumours. Whereas the histology and immunohistochemistry of these tumours are well documented, almost nothing is known about the molecular mechanisms involved in their pathogenesis. To characterize the genes altered in these malignancies, a genome‐wide cDNA library was generated by suppression subtractive hybridization and a set of differentially expressed clones was isolated. These were then used to produce custom‐spotted cDNA arrays. Genes deregulated in endometrial stromal sarcomas were identified by cDNA array hybridization and were confirmed by quantitative real‐time PCR analyses and in situ hybridization. Following cDNA array analysis, more than 300 genes deregulated in endometrial stromal sarcoma were selected and sequenced. Among the most significantly deregulated genes were those of secreted frizzled‐related proteins (SFRPs), in particular secreted frizzled‐related protein 4 (SFRP4). SFRPs are putative modulators of the Wnt‐signalling pathway and play a role in different cellular events including cell proliferation. Compared with normal endometrium, the expression of SFRP4 was decreased in both low‐grade endometrial stromal sarcoma (ESS; n = 10) and undifferentiated endometrial sarcoma (UES; n = 4), being lower in the latter more aggressive form. These results were verified on paraffin wax‐embedded tissue by quantitative real‐time PCR analysis and in situ hybridization. Furthermore, the expression of β‐catenin, an important component of the Wnt‐signalling pathway, was regulated in an opposite manner to SFRP4, being particularly increased in undifferentiated sarcomas. The activation of the Wnt‐signalling pathway was additionally supported by the immunohistochemical demonstration that β‐catenin was translocated to the nucleus in UES. SFRP4 may therefore be a putative tumour suppressor involved in deregulation of the Wnt pathway and in the pathogenesis of ESS and UES. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.