Clinical significance of CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma

Francesca Diomedi-Camassei, Heather P. McDowell, Maria A. De loris, Stefania Uccini, Pierluigi Altavista, Giuseppe Raschellà, Roberta Vitali, Olga Mannarino, Luigi De Sio, Denis A. Cozzi, Alberto Donfrancesco, Alessandro Inserra, Francesco Callea, Carlo Dominici

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Abstract

Purpose:The CXC chemokine receptor-4 (CXCR4)/stromal-derived factor-1 and c-Met/hepatocyte growth factor axes promote the metastatic potential of rhabdomyosarcoma cell lines in experimental models, but no data are available on their role in rhabdomyosarcoma tumors. The expressions of CXCR4 and c-Met were evaluated in primary tumors and isolated tumor cells in marrow, and were correlated with clinicopathologic variables and survival. Experimental Design: Forty patients with recently diagnosed rhabdomyosarcoma were retrospectively enrolled. CXCR4 and c-Met expression was investigated in primary tumors by immunohistochemistry, in isolated marrow-infiltrating tumor cells using double-label immunocytology. Results were expressed as the mean percentage of immunostained tumor cells. Results: CXCR4 and c-Met were expressed in ≥5% of tumor cells from 40 of 40 tumors, with 14 of 40 cases showing ≥50% of immunostained tumor cells (high expression). High CXCR4 expression correlated with alveolar histology (P - 0.006), unfavorable primary site (P = 0.009), advanced group (P <0.001), marrow involvement (P = 0.007), and shorter overall survival and event-free survival (P <0.001); high c-Met expression correlated with alveolar histology (P = 0.005), advanced group (P = 0.04), and marrow involvement (P = 0.02). In patients with a positive diagnosis for isolated tumor cells in marrow (n - 16), a significant enrichment in the percentage of CXCR4-positive (P - 0.001) and c-Met- positive (P = 0.003) tumor cells was shown in marrow aspirates compared with the corresponding primary tumors. Conclusions: CXCR4 and c-Met are widely expressed in both rhabdomyosarcoma subtypes and, at higher levels, in isolated marrow-infiltrating tumor cells. High levels of expression are associated with unfavorable clinical features, tumor marrow involvement and, only for CXCR4, poor outcome. In rhabdomyosarcoma, CXCR4 and c-Met represent novel exploitable targets for disease-directed therapy.

Original languageEnglish
Pages (from-to)4119-4127
Number of pages9
JournalClinical Cancer Research
Volume14
Issue number13
DOIs
Publication statusPublished - Jul 1 2008

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CXCR4 Receptors
Rhabdomyosarcoma
Bone Marrow
Neoplasms
Histology
Hepatocyte Growth Factor
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Diomedi-Camassei, F., McDowell, H. P., De loris, M. A., Uccini, S., Altavista, P., Raschellà, G., ... Dominici, C. (2008). Clinical significance of CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma. Clinical Cancer Research, 14(13), 4119-4127. https://doi.org/10.1158/1078-0432.CCR-07-4446

Clinical significance of CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma. / Diomedi-Camassei, Francesca; McDowell, Heather P.; De loris, Maria A.; Uccini, Stefania; Altavista, Pierluigi; Raschellà, Giuseppe; Vitali, Roberta; Mannarino, Olga; De Sio, Luigi; Cozzi, Denis A.; Donfrancesco, Alberto; Inserra, Alessandro; Callea, Francesco; Dominici, Carlo.

In: Clinical Cancer Research, Vol. 14, No. 13, 01.07.2008, p. 4119-4127.

Research output: Contribution to journalArticle

Diomedi-Camassei, F, McDowell, HP, De loris, MA, Uccini, S, Altavista, P, Raschellà, G, Vitali, R, Mannarino, O, De Sio, L, Cozzi, DA, Donfrancesco, A, Inserra, A, Callea, F & Dominici, C 2008, 'Clinical significance of CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma', Clinical Cancer Research, vol. 14, no. 13, pp. 4119-4127. https://doi.org/10.1158/1078-0432.CCR-07-4446
Diomedi-Camassei F, McDowell HP, De loris MA, Uccini S, Altavista P, Raschellà G et al. Clinical significance of CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma. Clinical Cancer Research. 2008 Jul 1;14(13):4119-4127. https://doi.org/10.1158/1078-0432.CCR-07-4446
Diomedi-Camassei, Francesca ; McDowell, Heather P. ; De loris, Maria A. ; Uccini, Stefania ; Altavista, Pierluigi ; Raschellà, Giuseppe ; Vitali, Roberta ; Mannarino, Olga ; De Sio, Luigi ; Cozzi, Denis A. ; Donfrancesco, Alberto ; Inserra, Alessandro ; Callea, Francesco ; Dominici, Carlo. / Clinical significance of CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 13. pp. 4119-4127.
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abstract = "Purpose:The CXC chemokine receptor-4 (CXCR4)/stromal-derived factor-1 and c-Met/hepatocyte growth factor axes promote the metastatic potential of rhabdomyosarcoma cell lines in experimental models, but no data are available on their role in rhabdomyosarcoma tumors. The expressions of CXCR4 and c-Met were evaluated in primary tumors and isolated tumor cells in marrow, and were correlated with clinicopathologic variables and survival. Experimental Design: Forty patients with recently diagnosed rhabdomyosarcoma were retrospectively enrolled. CXCR4 and c-Met expression was investigated in primary tumors by immunohistochemistry, in isolated marrow-infiltrating tumor cells using double-label immunocytology. Results were expressed as the mean percentage of immunostained tumor cells. Results: CXCR4 and c-Met were expressed in ≥5{\%} of tumor cells from 40 of 40 tumors, with 14 of 40 cases showing ≥50{\%} of immunostained tumor cells (high expression). High CXCR4 expression correlated with alveolar histology (P - 0.006), unfavorable primary site (P = 0.009), advanced group (P <0.001), marrow involvement (P = 0.007), and shorter overall survival and event-free survival (P <0.001); high c-Met expression correlated with alveolar histology (P = 0.005), advanced group (P = 0.04), and marrow involvement (P = 0.02). In patients with a positive diagnosis for isolated tumor cells in marrow (n - 16), a significant enrichment in the percentage of CXCR4-positive (P - 0.001) and c-Met- positive (P = 0.003) tumor cells was shown in marrow aspirates compared with the corresponding primary tumors. Conclusions: CXCR4 and c-Met are widely expressed in both rhabdomyosarcoma subtypes and, at higher levels, in isolated marrow-infiltrating tumor cells. High levels of expression are associated with unfavorable clinical features, tumor marrow involvement and, only for CXCR4, poor outcome. In rhabdomyosarcoma, CXCR4 and c-Met represent novel exploitable targets for disease-directed therapy.",
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T1 - Clinical significance of CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma

AU - Diomedi-Camassei, Francesca

AU - McDowell, Heather P.

AU - De loris, Maria A.

AU - Uccini, Stefania

AU - Altavista, Pierluigi

AU - Raschellà, Giuseppe

AU - Vitali, Roberta

AU - Mannarino, Olga

AU - De Sio, Luigi

AU - Cozzi, Denis A.

AU - Donfrancesco, Alberto

AU - Inserra, Alessandro

AU - Callea, Francesco

AU - Dominici, Carlo

PY - 2008/7/1

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N2 - Purpose:The CXC chemokine receptor-4 (CXCR4)/stromal-derived factor-1 and c-Met/hepatocyte growth factor axes promote the metastatic potential of rhabdomyosarcoma cell lines in experimental models, but no data are available on their role in rhabdomyosarcoma tumors. The expressions of CXCR4 and c-Met were evaluated in primary tumors and isolated tumor cells in marrow, and were correlated with clinicopathologic variables and survival. Experimental Design: Forty patients with recently diagnosed rhabdomyosarcoma were retrospectively enrolled. CXCR4 and c-Met expression was investigated in primary tumors by immunohistochemistry, in isolated marrow-infiltrating tumor cells using double-label immunocytology. Results were expressed as the mean percentage of immunostained tumor cells. Results: CXCR4 and c-Met were expressed in ≥5% of tumor cells from 40 of 40 tumors, with 14 of 40 cases showing ≥50% of immunostained tumor cells (high expression). High CXCR4 expression correlated with alveolar histology (P - 0.006), unfavorable primary site (P = 0.009), advanced group (P <0.001), marrow involvement (P = 0.007), and shorter overall survival and event-free survival (P <0.001); high c-Met expression correlated with alveolar histology (P = 0.005), advanced group (P = 0.04), and marrow involvement (P = 0.02). In patients with a positive diagnosis for isolated tumor cells in marrow (n - 16), a significant enrichment in the percentage of CXCR4-positive (P - 0.001) and c-Met- positive (P = 0.003) tumor cells was shown in marrow aspirates compared with the corresponding primary tumors. Conclusions: CXCR4 and c-Met are widely expressed in both rhabdomyosarcoma subtypes and, at higher levels, in isolated marrow-infiltrating tumor cells. High levels of expression are associated with unfavorable clinical features, tumor marrow involvement and, only for CXCR4, poor outcome. In rhabdomyosarcoma, CXCR4 and c-Met represent novel exploitable targets for disease-directed therapy.

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