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 language | English |
|---|---|
| Pages (from-to) | 4119-4127 |
| Number of pages | 9 |
| Journal | Clinical Cancer Research |
| Volume | 14 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - Jul 1 2008 |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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
Y1 - 2008/7/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=48249134045&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48249134045&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-07-4446
DO - 10.1158/1078-0432.CCR-07-4446
M3 - Article
VL - 14
SP - 4119
EP - 4127
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 13
ER -