Skip to main content
Erschienen in: Clinical and Translational Oncology 6/2015

01.06.2015 | Research Article

The clinical pathological significance of FRAT1 and ROR2 expression in cartilage tumors

verfasst von: L. He, Z. Yang, J. Zhou, W. Wang

Erschienen in: Clinical and Translational Oncology | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Chondrosarcoma is a malignant bone tumor with poor prognosis. Surgical treatment is the first choice for chondrosarcomas. Chondrosarcoma is not sensitive to chemotherapy and radiotherapy. Identification of biological markers is important for the early diagnosis and targeted treatment of chondrosarcoma. This study investigated the protein expression and clinicopathological significance of ROR2 and FRAT1 in 59 chondrosarcomas and 33 osteochondromas.

Methods

ROR2 and FRAT1 protein expression in tissues was measured by immunohistochemistry.

Results

The percentage of positive ROR2 and FRAT1 expression was significantly higher in patients with chondrosarcoma than in patients with osteochondroma (P < 0.01). The percentage of positive ROR2 and FRAT1 expression was significantly lower in patients with histological grade I, AJCC stage I/II stage, Enneking stage I, non-metastatic and invasive chondrosarcoma than patients with histological grade III, AJCC stage III/IV, Enneking stage II + III, metastatic and invasive chondrosarcoma (P < 0.05 or P < 0.01). ROR2 expression was positively correlated with FRAT1 expression in chondrosarcoma. Kaplan–Meier survival analysis demonstrated that histological grade, AJCC stage, Enneking stage, metastasis, invasion, and ROR2 and FRAT1 expression significantly correlated with a short mean survival time of patients with chondrosarcoma (P < 0.05 or P < 0.01). Cox multivariate analysis showed that positive ROR2 and FRAT1 expression was an independent prognostic factor that negatively correlated with postoperative survival and positively correlated with mortality.

Conclusion

Positive ROR2 and FRAT1 expression is associated with the progression and poor prognosis of chondrosarcoma.
Literatur
1.
Zurück zum Zitat Pritchard DJ, Lunke RJ, Taylor WF, Dahlin DC, Medley BE. Chondrosarcoma: a clinicopathologic and statistical analysis. Cancer. 1980;45:149–57.CrossRefPubMed Pritchard DJ, Lunke RJ, Taylor WF, Dahlin DC, Medley BE. Chondrosarcoma: a clinicopathologic and statistical analysis. Cancer. 1980;45:149–57.CrossRefPubMed
2.
Zurück zum Zitat Sekharappa V, Amritanand R, Krishnan V, David KS. Symptomatic solitary osteochondroma of the subaxial cervical spine in a 52-year-old patient. Asian Spine J. 2014;8:84–8.CrossRefPubMedCentralPubMed Sekharappa V, Amritanand R, Krishnan V, David KS. Symptomatic solitary osteochondroma of the subaxial cervical spine in a 52-year-old patient. Asian Spine J. 2014;8:84–8.CrossRefPubMedCentralPubMed
3.
4.
Zurück zum Zitat Ford CE, Qian Ma SS, Quadir A, Ward RL. The dual role of the novel Wnt receptor tyrosine kinase, ROR2, in human carcinogenesis. Int J Cancer. 2013;133:779–87.CrossRefPubMed Ford CE, Qian Ma SS, Quadir A, Ward RL. The dual role of the novel Wnt receptor tyrosine kinase, ROR2, in human carcinogenesis. Int J Cancer. 2013;133:779–87.CrossRefPubMed
5.
Zurück zum Zitat Niehrs C. The complex world of WNT receptor signaling. Nat Rev Mol Cell Biol. 2012;13:767–79.CrossRefPubMed Niehrs C. The complex world of WNT receptor signaling. Nat Rev Mol Cell Biol. 2012;13:767–79.CrossRefPubMed
6.
Zurück zum Zitat Ren D, Minami Y, Nishita M. Critical role of Wnt5a-Ror2 signaling in motility and invasiveness of carcinoma cells following snail-mediated epithelial-mesenchymal transition. Genes Cells. 2011;16:304–15.CrossRefPubMed Ren D, Minami Y, Nishita M. Critical role of Wnt5a-Ror2 signaling in motility and invasiveness of carcinoma cells following snail-mediated epithelial-mesenchymal transition. Genes Cells. 2011;16:304–15.CrossRefPubMed
7.
Zurück zum Zitat Saitoh T, Mine T, Katoh M. Molecular cloning and expression of proto-oncogene FRAT1 in human cancer. Int J Oncol. 2002;20:785–9.PubMed Saitoh T, Mine T, Katoh M. Molecular cloning and expression of proto-oncogene FRAT1 in human cancer. Int J Oncol. 2002;20:785–9.PubMed
8.
Zurück zum Zitat van Amerongen R, Nawijn MC, Lambooij JP, Proost N, Jonkers J, Berns A. Frat oncoproteins act at the crossroad of canonical and noncanonical Wnt-signaling pathways. Oncogene. 2010;29:93–104.CrossRefPubMed van Amerongen R, Nawijn MC, Lambooij JP, Proost N, Jonkers J, Berns A. Frat oncoproteins act at the crossroad of canonical and noncanonical Wnt-signaling pathways. Oncogene. 2010;29:93–104.CrossRefPubMed
10.
Zurück zum Zitat O’Connell MP, Fiori JL, Xu M, Carter AD, Frank BP, Camilli TC, et al. The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma. Oncogene. 2010;29:34–44.CrossRefPubMedCentralPubMed O’Connell MP, Fiori JL, Xu M, Carter AD, Frank BP, Camilli TC, et al. The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma. Oncogene. 2010;29:34–44.CrossRefPubMedCentralPubMed
11.
Zurück zum Zitat Wright TM, Brannon AR, Gordan JD, Mikels AJ, Mitchell C, Chen S, et al. Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma. Oncogene. 2009;28:2513–23.CrossRefPubMedCentralPubMed Wright TM, Brannon AR, Gordan JD, Mikels AJ, Mitchell C, Chen S, et al. Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma. Oncogene. 2009;28:2513–23.CrossRefPubMedCentralPubMed
12.
Zurück zum Zitat Katoh Y, Katoh M. Comparative integromics on FAT1, FAT2, FAT3 and FAT4. Int J Mol Med. 2006;18:523–8.PubMed Katoh Y, Katoh M. Comparative integromics on FAT1, FAT2, FAT3 and FAT4. Int J Mol Med. 2006;18:523–8.PubMed
13.
Zurück zum Zitat Edris B, Espinosa I, Mühlenberg T, Mikels A, Lee CH, Steigen SE, et al. ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour. J Pathol. 2012;227:223–33.CrossRefPubMedCentralPubMed Edris B, Espinosa I, Mühlenberg T, Mikels A, Lee CH, Steigen SE, et al. ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour. J Pathol. 2012;227:223–33.CrossRefPubMedCentralPubMed
14.
Zurück zum Zitat Lu BJ, Wang YQ, Wei XJ, Rong LQ, Wei D, Yan CM, et al. Expression of WNT-5a and ROR2 correlates with disease severity in osteosarcoma. Mol Med Rep. 2012;5:1033–6.PubMedCentralPubMed Lu BJ, Wang YQ, Wei XJ, Rong LQ, Wei D, Yan CM, et al. Expression of WNT-5a and ROR2 correlates with disease severity in osteosarcoma. Mol Med Rep. 2012;5:1033–6.PubMedCentralPubMed
15.
Zurück zum Zitat Morioka K, Tanikawa C, Ochi K, Daigo Y, Katagiri T, Kawano H, et al. Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma. Cancer Sci. 2009;100:1227–33.CrossRefPubMed Morioka K, Tanikawa C, Ochi K, Daigo Y, Katagiri T, Kawano H, et al. Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma. Cancer Sci. 2009;100:1227–33.CrossRefPubMed
16.
Zurück zum Zitat Lara E, Calvanese V, Huidobro C, Fernández AF, Moncada-Pazos A, Obaya AJ, et al. Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer. Mol Cancer. 2010;9:170.CrossRefPubMedCentralPubMed Lara E, Calvanese V, Huidobro C, Fernández AF, Moncada-Pazos A, Obaya AJ, et al. Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer. Mol Cancer. 2010;9:170.CrossRefPubMedCentralPubMed
17.
Zurück zum Zitat Geng M, Cao YC, Chen YJ, Jiang H, Bi LQ, Liu XH. Loss of Wnt5a and Ror2 protein in hepatocellular carcinoma associated with poor prognosis. World J Gastroenterol. 2012;18:1328–38.CrossRefPubMedCentralPubMed Geng M, Cao YC, Chen YJ, Jiang H, Bi LQ, Liu XH. Loss of Wnt5a and Ror2 protein in hepatocellular carcinoma associated with poor prognosis. World J Gastroenterol. 2012;18:1328–38.CrossRefPubMedCentralPubMed
18.
Zurück zum Zitat Daneshmanesh AH, Porwit A, Hojjat-Farsangi M, Jeddi-Tehrani M, Tamm KP, Grandér D, et al. Orphan receptor tyrosine kinases ROR1 and ROR2 in hematological malignancies. Leuk Lymphoma. 2013;54:843–50.CrossRefPubMed Daneshmanesh AH, Porwit A, Hojjat-Farsangi M, Jeddi-Tehrani M, Tamm KP, Grandér D, et al. Orphan receptor tyrosine kinases ROR1 and ROR2 in hematological malignancies. Leuk Lymphoma. 2013;54:843–50.CrossRefPubMed
19.
Zurück zum Zitat Endo M, Doi R, Nishita M, Minami Y. Ror family receptor tyrosine kinases regulate the maintenance of neural progenitor cells in the developing neocortex. Cell Sci. 2012;125:2017–29.CrossRef Endo M, Doi R, Nishita M, Minami Y. Ror family receptor tyrosine kinases regulate the maintenance of neural progenitor cells in the developing neocortex. Cell Sci. 2012;125:2017–29.CrossRef
20.
Zurück zum Zitat Al-Shawi R, Ashton SV, Underwood C, Simons JP. Expression of the Ror1 and Ror2 receptor tyrosine kinase genes during mouse development. Dev Genes Evol. 2001;211:161–71.CrossRefPubMed Al-Shawi R, Ashton SV, Underwood C, Simons JP. Expression of the Ror1 and Ror2 receptor tyrosine kinase genes during mouse development. Dev Genes Evol. 2001;211:161–71.CrossRefPubMed
21.
Zurück zum Zitat Saitoh T, Katoh M. FRAT1 and FRAT2, clustered in human chromosome 10q24.1 region, are up-regulated in gastric cancer. Int J Oncol. 2001;19:311–5.PubMed Saitoh T, Katoh M. FRAT1 and FRAT2, clustered in human chromosome 10q24.1 region, are up-regulated in gastric cancer. Int J Oncol. 2001;19:311–5.PubMed
22.
Zurück zum Zitat van Amerongen R, Nawijn M, Franca-Koh J, Zevenhoven J, van der Gulden H, Jonkers J, et al. Frat is dispensable for canonical Wnt signaling in mammals. Genes Dev. 2005;19:425–30.CrossRefPubMedCentralPubMed van Amerongen R, Nawijn M, Franca-Koh J, Zevenhoven J, van der Gulden H, Jonkers J, et al. Frat is dispensable for canonical Wnt signaling in mammals. Genes Dev. 2005;19:425–30.CrossRefPubMedCentralPubMed
23.
Zurück zum Zitat Wang Y, Liu S, Zhu H, Zhang W, Zhang G, Zhou X, et al. FRAT1 overexpression leads to aberrant activation of beta-catenin/TCF pathway in esophageal squamous cell carcinoma. Int J Cancer. 2008;123:561–8.CrossRefPubMed Wang Y, Liu S, Zhu H, Zhang W, Zhang G, Zhou X, et al. FRAT1 overexpression leads to aberrant activation of beta-catenin/TCF pathway in esophageal squamous cell carcinoma. Int J Cancer. 2008;123:561–8.CrossRefPubMed
24.
Zurück zum Zitat Zhang Y, Han Y, Zheng R, Yu JH, Miao Y, Wang L, et al. Expression of Frat1 correlates with expression of β-catenin and is associated with a poor clinical outcome in human SCC and AC. Tumour Biol. 2012;33:1437–44.CrossRefPubMed Zhang Y, Han Y, Zheng R, Yu JH, Miao Y, Wang L, et al. Expression of Frat1 correlates with expression of β-catenin and is associated with a poor clinical outcome in human SCC and AC. Tumour Biol. 2012;33:1437–44.CrossRefPubMed
25.
Zurück zum Zitat Wang Y, Hewitt SM, Liu S, Zhou X, Zhu H, Zhou C, et al. Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours. Br J Cancer. 2006;94:686–91.PubMedCentralPubMed Wang Y, Hewitt SM, Liu S, Zhou X, Zhu H, Zhou C, et al. Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours. Br J Cancer. 2006;94:686–91.PubMedCentralPubMed
26.
Zurück zum Zitat Guo G, Mao X, Wang P, Liu B, Zhang X, Jiang X, et al. The expression profile of FRAT1 in human gliomas. Brain Res. 2010;1320:152–8.CrossRefPubMed Guo G, Mao X, Wang P, Liu B, Zhang X, Jiang X, et al. The expression profile of FRAT1 in human gliomas. Brain Res. 2010;1320:152–8.CrossRefPubMed
Metadaten
Titel
The clinical pathological significance of FRAT1 and ROR2 expression in cartilage tumors
verfasst von
L. He
Z. Yang
J. Zhou
W. Wang
Publikationsdatum
01.06.2015
Verlag
Springer Milan
Erschienen in
Clinical and Translational Oncology / Ausgabe 6/2015
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-014-1254-y

Weitere Artikel der Ausgabe 6/2015

Clinical and Translational Oncology 6/2015 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.