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Erschienen in: Medical Oncology 1/2011

01.12.2011 | Original Paper

Expression change of ezrin as a prognostic factor in primary osteosarcoma

Erschienen in: Medical Oncology | Sonderheft 1/2011

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Abstract

Osteosarcoma is a life-threatening malignancy that most often occurs in teenagers. Ezrin is a cytoskeleton linker protein that is actively involved in the metastatic capacity of cancer cells. In this study, we investigated the expression change of ezrin after preoperative chemotherapy and its prognostic value in patients with primary osteosarcoma. Ezrin mRNA expression level of initial biopsy specimens and resected tumor specimens after preoperative chemotherapy of 25 patients who had primary osteosarcoma with ezrin expression was detected by semiquantitative reverse transcription polymerase chain reaction (RT–PCR) to evaluate the expression change of ezrin. In addition, the prognostic factors and the relationship between the expression change of ezrin and the clinical characteristics were analyzed. Expression change of ezrin was found in 64% of all 25 patients. The expression change of ezrin had good relation with histology (P = 0.037), grade (P = 0.006), chemotherapy response (P = 0.017), and metastasis or recurrence (P = 0.041). The 2-year overall survival and event-free survival were associated with expression change of ezrin (P = 0.001 and P = 0.002, respectively) and response to preoperative chemotherapy (P = 0.001 and P = 0.012, respectively). Our findings suggest that expression change of ezrin is an independent positive prognostic factor in non-metastatic osteosarcoma.
Literatur
1.
Zurück zum Zitat Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. National cancer data base report. Clin Orthop Relat Res. 2007;459:40–7.PubMedCrossRef Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. National cancer data base report. Clin Orthop Relat Res. 2007;459:40–7.PubMedCrossRef
2.
Zurück zum Zitat Meyers PA, et al. Chemotherapy for nonmetastatic osteogenic sarcoma: the memorial sloan-kettering experience. J Clin Oncol. 1992;10:5–15.PubMed Meyers PA, et al. Chemotherapy for nonmetastatic osteogenic sarcoma: the memorial sloan-kettering experience. J Clin Oncol. 1992;10:5–15.PubMed
3.
Zurück zum Zitat Bacci G, et al. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006;106:1154–61.PubMedCrossRef Bacci G, et al. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006;106:1154–61.PubMedCrossRef
4.
Zurück zum Zitat Kalifa C, et al. Chemotherapy in osteogenic sarcoma: the experience of the pediatric department of the Gustave Roussy institute. Cancer Treat Res. 1993;62:347–9.PubMedCrossRef Kalifa C, et al. Chemotherapy in osteogenic sarcoma: the experience of the pediatric department of the Gustave Roussy institute. Cancer Treat Res. 1993;62:347–9.PubMedCrossRef
5.
Zurück zum Zitat Bieling P, et al. Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol. 1996;14:848–58.PubMed Bieling P, et al. Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol. 1996;14:848–58.PubMed
6.
Zurück zum Zitat Taylor WF, et al. Prognostic variables in osteosarcoma: a multi-institutional study. J Natl Cancer Inst. 1989;81:21–30.PubMedCrossRef Taylor WF, et al. Prognostic variables in osteosarcoma: a multi-institutional study. J Natl Cancer Inst. 1989;81:21–30.PubMedCrossRef
7.
Zurück zum Zitat Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008;134:281–97.PubMedCrossRef Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008;134:281–97.PubMedCrossRef
8.
Zurück zum Zitat Buddingh EP, et al. Prognostic factors in pulmonary metastasized high-grade osteosarcoma. Pediatr Blood Cancer. 2010;54:216–21.PubMed Buddingh EP, et al. Prognostic factors in pulmonary metastasized high-grade osteosarcoma. Pediatr Blood Cancer. 2010;54:216–21.PubMed
9.
Zurück zum Zitat Mangeat P, Roy C, Martin M. ERM proteins in cell adhesion and membrane dynamics. Trends Cell Biol. 1999;9:187–92.PubMedCrossRef Mangeat P, Roy C, Martin M. ERM proteins in cell adhesion and membrane dynamics. Trends Cell Biol. 1999;9:187–92.PubMedCrossRef
10.
Zurück zum Zitat Vaheri A, et al. The ezrin protein family: membrane-cytoskeleton interactions and disease associations. Curr Opin Cell Biol. 1997;9:659–66.PubMedCrossRef Vaheri A, et al. The ezrin protein family: membrane-cytoskeleton interactions and disease associations. Curr Opin Cell Biol. 1997;9:659–66.PubMedCrossRef
11.
Zurück zum Zitat Bretscher A, Edwards K, Fehon RG. ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol. 2002;3:586–99.PubMedCrossRef Bretscher A, Edwards K, Fehon RG. ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol. 2002;3:586–99.PubMedCrossRef
12.
Zurück zum Zitat Gautreau A, et al. Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci USA. 1999;96:7300–5.PubMedCrossRef Gautreau A, et al. Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci USA. 1999;96:7300–5.PubMedCrossRef
13.
Zurück zum Zitat Wang JW, et al. Identification of metastasis-associated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1. Cancer Lett. 2009;281:71–81.PubMedCrossRef Wang JW, et al. Identification of metastasis-associated proteins involved in gallbladder carcinoma metastasis by proteomic analysis and functional exploration of chloride intracellular channel 1. Cancer Lett. 2009;281:71–81.PubMedCrossRef
14.
15.
Zurück zum Zitat Ilmonen S, Vaheri A, Asko-Seljavaara S, Carpen O. Ezrin in primary cutaneous melanoma. Mod Pathol. 2005;18:503–10.PubMedCrossRef Ilmonen S, Vaheri A, Asko-Seljavaara S, Carpen O. Ezrin in primary cutaneous melanoma. Mod Pathol. 2005;18:503–10.PubMedCrossRef
16.
Zurück zum Zitat Weng WH, Ahlen J, Astrom K, Lui WO, Larsson C. Prognostic impact of immunohistochemical expression of ezrin in highly malignant soft tissue sarcomas. Clin Cancer Res. 2005;11:6198–204.PubMedCrossRef Weng WH, Ahlen J, Astrom K, Lui WO, Larsson C. Prognostic impact of immunohistochemical expression of ezrin in highly malignant soft tissue sarcomas. Clin Cancer Res. 2005;11:6198–204.PubMedCrossRef
17.
Zurück zum Zitat Khanna C, et al. The membrane cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004;10:182–6.PubMedCrossRef Khanna C, et al. The membrane cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004;10:182–6.PubMedCrossRef
18.
Zurück zum Zitat Picci P, et al. Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy. Regional mapping of viable and nonviable tumor. Cancer. 1985;56:1515–21.PubMedCrossRef Picci P, et al. Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy. Regional mapping of viable and nonviable tumor. Cancer. 1985;56:1515–21.PubMedCrossRef
19.
Zurück zum Zitat Bacci G, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli’s 4th protocol. Eur J Cancer. 2001;37:2030–9.PubMedCrossRef Bacci G, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli’s 4th protocol. Eur J Cancer. 2001;37:2030–9.PubMedCrossRef
20.
Zurück zum Zitat Bielack SS, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 2002;20:627–9.CrossRef Bielack SS, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 2002;20:627–9.CrossRef
21.
Zurück zum Zitat Sohn JH, et al. Efficacy of pre- and postoperative chemotherapy in patients with osteosarcoma of the extremities. Cancer Res Treat. 2001;33:520–6. Sohn JH, et al. Efficacy of pre- and postoperative chemotherapy in patients with osteosarcoma of the extremities. Cancer Res Treat. 2001;33:520–6.
22.
Zurück zum Zitat Zhang Y, et al. The membrane-cytoskeleton organizer ezrin is necessary for hepatocellular carcinoma cell growth and invasiveness. J Cancer Res Clin Oncol. 2006;132:685–97.PubMedCrossRef Zhang Y, et al. The membrane-cytoskeleton organizer ezrin is necessary for hepatocellular carcinoma cell growth and invasiveness. J Cancer Res Clin Oncol. 2006;132:685–97.PubMedCrossRef
23.
Zurück zum Zitat Kim MS, Song WS, Cho WH, Lee SY, Jeon DG. Ezrin expression predicts survival in stage IIB osteosarcomas. Clin Orthop Relat Res. 2007;459:229–36.PubMedCrossRef Kim MS, Song WS, Cho WH, Lee SY, Jeon DG. Ezrin expression predicts survival in stage IIB osteosarcomas. Clin Orthop Relat Res. 2007;459:229–36.PubMedCrossRef
24.
Zurück zum Zitat Xu-dong S, et al. Expression of ezrin correlates with lung metastasis in Chinese patients with osteosarcoma. Clin Invest Med. 2009;32:180–8. Xu-dong S, et al. Expression of ezrin correlates with lung metastasis in Chinese patients with osteosarcoma. Clin Invest Med. 2009;32:180–8.
25.
Zurück zum Zitat Bentzen SM, et al. Prognostic factors in osteosarcomas. A regression analysis. Cancer. 1988;62:194–202.PubMedCrossRef Bentzen SM, et al. Prognostic factors in osteosarcomas. A regression analysis. Cancer. 1988;62:194–202.PubMedCrossRef
26.
Zurück zum Zitat Hauben EI, Weeden S, Pringle J, Van Marck EA, Hogendoorn PC. Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer. 2002;38:1218–25.PubMedCrossRef Hauben EI, Weeden S, Pringle J, Van Marck EA, Hogendoorn PC. Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer. 2002;38:1218–25.PubMedCrossRef
27.
Zurück zum Zitat Park HR, et al. Ezrin in osteosarcoma: comparison between conventional high-grade and central low-grade osteosarcoma. Pathol Res Pract. 2006;202:509–15.PubMedCrossRef Park HR, et al. Ezrin in osteosarcoma: comparison between conventional high-grade and central low-grade osteosarcoma. Pathol Res Pract. 2006;202:509–15.PubMedCrossRef
28.
Zurück zum Zitat Provisor AJ, et al. Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children’s Cancer Group. J Clin Oncol. 1997;15:76–84.PubMed Provisor AJ, et al. Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children’s Cancer Group. J Clin Oncol. 1997;15:76–84.PubMed
29.
Zurück zum Zitat Rosen G, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982;49:1221–30.PubMedCrossRef Rosen G, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982;49:1221–30.PubMedCrossRef
30.
Zurück zum Zitat Salas S, et al. Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas. Virchows Arch. 2007;451:999–1007.PubMedCrossRef Salas S, et al. Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas. Virchows Arch. 2007;451:999–1007.PubMedCrossRef
Metadaten
Titel
Expression change of ezrin as a prognostic factor in primary osteosarcoma
Publikationsdatum
01.12.2011
Erschienen in
Medical Oncology / Ausgabe Sonderheft 1/2011
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9684-z

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