nach oben

Erschienen in:

01.12.2007 | Original Article

Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas

verfasst von: Sébastien Salas, Catherine Bartoli, Jean-Laurent Deville, Jean Gaudart, Fréderic Fina, Arlette Calisti, Gérard Bollini, Georges Curvale, Jean-Claude Gentet, Florence Duffaud, Dominique Figarella-Branger, Corinne Bouvier

Erschienen in: Virchows Archiv | Ausgabe 6/2007

Einloggen, um Zugang zu erhalten

Abstract

Ezrin is a cytoskeleton linker protein that is actively involved in the metastatic process of cancer cells. We have searched for a prognostic value of ezrin and some of its partners: α-smooth muscle actin and CD44H in 37 patients with an osteosarcoma. Automate immunohistochemistry (IHC) with anti-ezrin, α-smooth muscle actin and CD44H antibodies was performed in 66 specimens: 37 biopsies before chemotherapy, 16 resected tumours of “poor” responders and 13 metastases. The messenger RNA (mRNA) levels of ezrin of 13 frozen biopsies and 4 metastases were evaluated by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). All results were correlated to the following clinical data. Ezrin expression by IHC was found in 62% of 37 biopsies in the different histological subtypes. A good correlation was found between positive or negative samples by IHC and mRNA levels. Ezrin expression was recorded in 84.5% of metastastic samples. The mean expression of ezrin was higher in metastases than biopsies (p = 0.024). In multivariate analysis, ezrin was an independent prognostic marker for event-free survival and overall survival (OS) with p < 0.001 and p = 0.003, respectively, and α-smooth muscle actin for OS only (p = 0.024). Our findings suggest that ezrin and α-smooth muscle actin are predictive IHC prognostic markers for patients with an osteosarcoma.

Antonescu CR, Erlandson RA, Huvos AG (1997) Primary leiomyosarcoma of bone: a clinicopathologic, immunohistochemical, and ultrastructural study of 33 patients and a literature review. Am J Surg Pathol 21:1281–1294PubMedCrossRef

Bacci G, Mercuri M, Briccoli A, Ferrari S, Bertoni F, Donati D, Monti C, Zanoni A, Forni C, Manfrini M (1997) Osteogenic sarcoma of the extremity with detectable lung metastases at presentation. Results of treatment of 23 patients with chemotherapy followed by simultaneous resection of primary and metastatic lesions. Cancer 79:245–254PubMedCrossRef

Bieling P, Rehan N, Winkler P, Helmke K, Maas R, Fuchs N, Bielack S, Heise U, Jurgens H, Treuner J, Romanowski R, Exner U, Kotz R, Winkler K (1996) Tumor size and prognosis in aggressively treated osteosarcoma. J Clin Oncol 14:848–858PubMed

Bouvier-Labit C, Liprandi A, Monti G, Pellissier JF, Figarella-Branger D (2002) CD44H is expressed by cells of the oligodendrocyte lineage and by oligodendrogliomas in humans. J Neurooncol 60:127–134PubMedCrossRef

Bridge JA, Nelson M, McComb E, McGuire MH, Rosenthal H, Vergara G, Maale GE, Spanier S, Neff JR (1997) Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature. Cancer Genet Cytogenet 95:74–87PubMedCrossRef

Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159PubMedCrossRef

Eikmans M, Baelde HJ, Hagen EC, Paul LC, Eilers PH, De Heer E, Bruijn JA (2003) Renal mRNA levels as prognostic tools in kidney diseases. J Am Soc Nephrol 14:899–907PubMedCrossRef

Greenland S, Mickey RM (1989) Re: “The impact of confounder selection criteria on effect estimation. Am J Epidemiol 130:1066PubMed

Harris MB, Gieser P, Goorin AM, Ayala A, Shochat SJ, Ferguson WS, Holbrook T, Link MP (1998) Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study. J Clin Oncol 16:3641–3648PubMed

10.

Hasegawa T, Hirose T, Seki K, Hizawa K, Ishii S, Wakabayashi J (1997) Histological and immunohistochemical diversities, and proliferative activity and grading in osteosarcomas. Cancer Detect Prev 21:280–287PubMed

11.

Hunter KW (2004) Ezrin, a key component in tumor metastasis. Trends Mol Med 10:201–204PubMedCrossRef

12.

Ilmonen S, Vaheri A, Asko-Seljavaara S, Carpen O (2005) Ezrin in primary cutaneous melanoma. Mod Pathol 18:503–510PubMedCrossRef

13.

Khanna C, Khan J, Nguyen P, Prehn J, Caylor J, Yeung C, Trepel J, Meltzer P, Helman L (2001) Metastasis-associated differences in gene expression in a murine model of osteosarcoma. Cancer Res 61:3750–3759PubMed

14.

Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A, Yeung C, Gorlick R, Hewitt SM, Helman LJ (2004) The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med 10:182–186PubMedCrossRef

15.

Kim HS, Park YB, Oh JH, Jeong J, Kim CJ, Lee SH (2002) Expression of CD44 isoforms correlates with the metastatic potential of osteosarcoma. Clin Orthop Relat Res 396:184–190PubMedCrossRef

16.

Kim MS, Song WS, Cho WH, Lee SY, Jeon DG (2007) Ezrin Expression Predicts Survival in Stage IIB Osteosarcomas. Clin Orthop Relat Res 459:229–236PubMedCrossRef

17.

Koon N, Schneider-Stock R, Sarlomo-Rikala M, Lasota J, Smolkin M, Petroni G, Zaika A, Boltze C, Meyer F, Andersson L, Knuutila S, Miettinen M, El-Rifai W (2004) Molecular targets for tumour progression in gastrointestinal stromal tumours. Gut 53:235–240PubMedCrossRef

18.

Kuryu M, Ozaki T, Nishida K, Shibahara M, Kawai A, Inoue H (1999) Expression of CD44 variants in osteosarcoma. J Cancer Res Clin Oncol 125:646–652PubMedCrossRef

19.

Le Deley M, Guinebretiere J, Gentet J, Pacquement H, Pichon F, Marec-Berard P, Entz-Werle N, Schmitt C, Brugieres L, Vanel D, Dupouy N, Tabone M et al (2007) SFOP OS94: a randomised trial comparing preoperative high-dose Methotrexate plus Doxorubicine to high-dose Methotrexate plus Etoposide and Ifosfamide in osteosarcoma patients. European J Cancer 43:752–761CrossRef

20.

Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, Pritchard J, Malpas JS, Baker AR, Kirkpatrick JA et al (1986) The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 314:1600–1606PubMedCrossRef

21.

Mangeat P, Roy C, Martin M (1999) ERM proteins in cell adhesion and membrane dynamics. Trends Cell Biol 9:187–192PubMedCrossRef

22.

Martin TA, Harrison G, Mansel RE, Jiang WG (2003) The role of the CD44/ezrin complex in cancer metastasis. Crit Rev Oncol Hematol 46:165–186PubMedCrossRef

23.

Meyers PA, Gorlick R (1997) Osteosarcoma. Pediatr Clin North Am 44:973–989PubMedCrossRef

24.

Meyers PA, Heller G, Healey J, Huvos A, Lane J, Marcove R, Applewhite A, Vlamis V, Rosen G (1992) Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering experience. J Clin Oncol 10:5–15PubMed

25.

Nathrath MH, Kuosaite V, Rosemann M, Kremer M, Poremba C, Wakana S, Yanagi M, Nathrath WB, Hofler H, Imai K, Atkinson MJ (2002) Two novel tumor suppressor gene loci on chromosome 6q and 15q in human osteosarcoma identified through comparative study of allelic imbalances in mouse and man. Oncogene 21:5975–5980PubMedCrossRef

26.

Pang ST, Fang X, Valdman A, Norstedt G, Pousette A, Egevad L, Ekman P (2004) Expression of ezrin in prostatic intraepithelial neoplasia. Urology 63:609–612PubMedCrossRef

27.

Park HR, Jung WW, Bacchini P, Bertoni F, Kim YW, Park YK (2006) Ezrin in osteosarcoma: comparison between conventional high-grade and central low-grade osteosarcoma. Pathol Res Pract 202:509–515PubMedCrossRef

28.

Peng TS, Qiu JS, Wu HX, Liang HZ, Luo CQ (2002) [Expressions of CD44s, MMP-9, and Ki-67: possible association with invasion, metastasis, and recurrence of osteosarcoma]. Ai Zheng 21:745–750PubMed

29.

Provisor AJ, Ettinger LJ, Nachman JB, Krailo MD, Makley JT, Yunis EJ, Huvos AG, Betcher DL, Baum ES, Kisker CT, Miser JS (1997) Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children’s Cancer Group. J Clin Oncol 15:76–84PubMed

30.

Rocchi P, Muracciole X, Fina F, Mulholland DJ, Karsenty G, Palmari J, Ouafik L, Bladou F, Martin PM (2004) Molecular analysis integrating different pathways associated with androgen-independent progression in LuCaP 23.1 xenograft. Oncogene 23:9111–9119PubMedCrossRef

31.

Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, Marcove RC, Lane JM, Mehta B, Urban C (1982) Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer 49:1221–1230PubMedCrossRef

32.

Rosen G, Marcove RC, Caparros B, Nirenberg A, Kosloff C, Huvos AG (1979) Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery. Cancer 43:2163–2177PubMedCrossRef

33.

Saeter G, Alvegard TA, Elomaa I, Stenwig AE, Holmstrom T, Solheim OP (1991) Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study. J Clin Oncol 9:1766–1775PubMed

34.

Shiratori H, Koshino T, Uesugi M, Nitto H, Saito T (2001) Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma-derived cell transplanted mice. Cancer Lett 170:177–182PubMedCrossRef

35.

Tarkkanen M, Karhu R, Kallioniemi A, Elomaa I, Kivioja AH, Nevalainen J, Bohling T, Karaharju E, Hyytinen E, Knuutila S et al (1995) Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization. Cancer Res 55:1334–1338PubMed

36.

Taylor WF, Ivins JC, Unni KK, Beabout JW, Golenzer HJ, Black LE (1989) Prognostic variables in osteosarcoma: a multi-institutional study. J Natl Cancer Inst 81:21–30PubMedCrossRef

37.

Vaheri A, Carpen O, Heiska L, Helander TS, Jaaskelainen J, Majander-Nordenswan P, Sainio M, Timonen T, Turunen O (1997) The ezrin protein family: membrane-cytoskeleton interactions and disease associations. Curr Opin Cell Biol 9:659–666PubMedCrossRef

38.

Wan X, Mendoza A, Khanna C, Helman LJ (2005) Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma. Cancer Res 65:2406–2411PubMedCrossRef

39.

Watanabe K, Tajino T, Sekiguchi M, Suzuki T (2000) h-Caldesmon as a specific marker for smooth muscle tumors. Comparison with other smooth muscle markers in bone tumors. Am J Clin Pathol 113:663–668PubMed

40.

Weber GF, Bronson RT, Ilagan J, Cantor H, Schmits R, Mak TW (2002) Absence of the CD44 gene prevents sarcoma metastasis. Cancer Res 62:2281–2286PubMed

41.

Weng WH, Ahlen J, Astrom K, Lui WO, Larsson C (2005) Prognostic impact of immunohistochemical expression of ezrin in highly malignant soft tissue sarcomas. Clin Cancer Res 11:6198–6204PubMedCrossRef

42.

Yamamura H, Yoshikawa H, Tatsuta M, Akedo H, Takahashi K (1998) Expression of the smooth muscle calponin gene in human osteosarcoma and its possible association with prognosis. Int J Cancer 79:245–250PubMedCrossRef

43.

Yu Y, Khan J, Khanna C, Helman L, Meltzer PS, Merlino G (2004) Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat Med 10:175–181PubMedCrossRef

Titel: Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas
verfasst von: Sébastien Salas
Catherine Bartoli
Jean-Laurent Deville
Jean Gaudart
Fréderic Fina
Arlette Calisti
Gérard Bollini
Georges Curvale
Jean-Claude Gentet
Florence Duffaud
Dominique Figarella-Branger
Corinne Bouvier
Publikationsdatum: 01.12.2007
Verlag: Springer-Verlag
Erschienen in: Virchows Archiv / Ausgabe 6/2007
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-007-0474-8

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas

Abstract

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2007

Hemorrhagic pulmonary oxalosis secondary to a noninvasive Aspergillus niger fungus ball

Comparison of RNA amplification techniques meeting the demands for the expression profiling of clinical cancer samples

Small intestinal CD4+ T-cell lymphoma: a rare distinctive clinicopathological entity associated with prolonged survival

Interaction between dendritic cells and nerve fibres in lymphoid organs after oral scrapie exposure

Biochemical and ultrastructural evidence of endoplasmic reticulum stress in LGMD2I

Adenocarcinoma of the minor duodenal papilla with intraepithelial spread to the pancreatic duct

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie