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Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2
Author(s) -
Salas Sébastien,
Jézéquel Pascal,
Campion Loic,
Deville JeanLaurent,
Chibon Frédéric,
Bartoli Catherine,
Gentet JeanClaude,
Charbonnel Catherine,
Gouraud Wilfried,
VoutsinosPorche Brigitte,
Brouchet Anne,
Duffaud Florence,
FigarellaBranger Dominique,
Bouvier Corinne
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24457
Subject(s) - osteosarcoma , chemotherapy , medicine , tissue microarray , immunohistochemistry , biopsy , polysomy , oncology , microarray , gene expression , pathology , gene , in situ hybridization , biology , biochemistry
The therapy regimen of high‐grade osteosarcoma includes chemotherapy followed by surgical resection and postoperative chemotherapy. The degree of necrosis following definitive surgery remains the only reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. The aim of this study was to find molecular markers able to classify patients with an osteosarcoma as good or poor responders to chemotherapy before beginning treatment. Gene expression screening of 20 nonmetastatic high‐grade osteosarcoma patients was performed using cDNA microarray. Expression of selected relevant genes was validated using QRT‐PCR. Immunohistochemistry on tissue microarrays sections of 73 biopsies was performed to investigate protein expression. Fluorescent in situ hybridization was performed for RPL8 gene. We have found that HSD17B10 gene expression was up‐regulated in poor responders and that immunohistochemistry expression of HSD17B10 on biopsy before treatment was correlatedto response to chemotherapy. Other results include correlationof IFITM2 , IFITM3 , and RPL8 gene expression to chemotherapy response. A statistical correlation was found between polysomy 8 or gain of RPL8 and good response to chemotherapy. These data suggest that HSD17B10, RPL8 , IFITM2 , and IFITM3 genes are involved in the response to the chemotherapy and that HSD17B10 may be a therapeutic target. RPL8 and IFITM2 may be useful in the assessment at diagnosis and for stratifying patients taking part in randomized trials. © 2009 UICC