Thorsten Jentzsch1, Bernhard Robl2, Maren Husmann2, Beata Bode-Lesniewska3, Bruno Fuchs2. 1. Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, Zürich, Switzerland Division of Trauma Surgery, Department of Surgery, University Hospital Zürich, Zürich, Switzerland thorsten.jentzsch@usz.ch. 2. Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, Zürich, Switzerland. 3. Institute of Surgical Pathology, University Hospital Zürich, Zürich, Switzerland.
Abstract
BACKGROUND: It is hardly possible to define osteosarcoma (OS) patients at greatest risk for non-response to chemotherapy, metastasis and short survival times. Our goal was the investigation of local expression of insulin-like growth factor (IGF-1) with regard to survival time of OS patients using a tissue microarray (TMA). MATERIALS AND METHODS: Tumor tissue specimens from surgical primary tumor resections were collected from patients with OS. A TMA was composed, sections were stained with rabbit anti-IGF-1 and grading was performed. Statistics involved Kaplan-Meier curves and the log-rank test. RESULTS: We analyzed immunohistochemical expression of local IGF-1 on a TMA based on surgical primary tumor resections of 67 OS patients. The mean clinical follow-up time was 98 months. Twenty-two (33%) OS patients stained negatively and 44 (66%) OS patients stained positively for IGF-1. Significantly shorter survival was detected with expression of IGF-1 (p=0.007). The 5-year survival rate for patients expressing IGF-1 was 63% compared to 92% in patients without expression of IGF-1. Non-responders to chemotherapy and patients with metastasis, who also stained positively for IGF-1 manifested a significantly (p=0.002 and p<0.0001, respectively) shorter survival. CONCLUSION: Expression of local IGF-1 in primary tumor tissue appears to significantly affect the aggressiveness of OS, may predict survival time and, above all, may discriminate patients with non-response to chemotherapy and metastasis. This represents the basis for successful patient selection with regard to the decision process for or against chemotherapy and the choice of the most effective therapeutic drug. It may be a more important marker of tumor progression and indicator of prognosis than serum IGF-1. Novel tumor markers and therapeutic agents targeting the local IGF-1 pathway may increase the likelihood of therapeutic success. Copyright
BACKGROUND: It is hardly possible to define osteosarcoma (OS) patients at greatest risk for non-response to chemotherapy, metastasis and short survival times. Our goal was the investigation of local expression of insulin-like growth factor (IGF-1) with regard to survival time of OS patients using a tissue microarray (TMA). MATERIALS AND METHODS:Tumor tissue specimens from surgical primary tumor resections were collected from patients with OS. A TMA was composed, sections were stained with rabbit anti-IGF-1 and grading was performed. Statistics involved Kaplan-Meier curves and the log-rank test. RESULTS: We analyzed immunohistochemical expression of local IGF-1 on a TMA based on surgical primary tumor resections of 67 OS patients. The mean clinical follow-up time was 98 months. Twenty-two (33%) OS patients stained negatively and 44 (66%) OS patients stained positively for IGF-1. Significantly shorter survival was detected with expression of IGF-1 (p=0.007). The 5-year survival rate for patients expressing IGF-1 was 63% compared to 92% in patients without expression of IGF-1. Non-responders to chemotherapy and patients with metastasis, who also stained positively for IGF-1 manifested a significantly (p=0.002 and p<0.0001, respectively) shorter survival. CONCLUSION: Expression of local IGF-1 in primary tumor tissue appears to significantly affect the aggressiveness of OS, may predict survival time and, above all, may discriminate patients with non-response to chemotherapy and metastasis. This represents the basis for successful patient selection with regard to the decision process for or against chemotherapy and the choice of the most effective therapeutic drug. It may be a more important marker of tumor progression and indicator of prognosis than serum IGF-1. Novel tumor markers and therapeutic agents targeting the local IGF-1 pathway may increase the likelihood of therapeutic success. Copyright
Authors: Arantzazu Alfranca; Lucia Martinez-Cruzado; Juan Tornin; Ander Abarrategi; Teresa Amaral; Enrique de Alava; Pablo Menendez; Javier Garcia-Castro; Rene Rodriguez Journal: Cell Mol Life Sci Date: 2015-05-03 Impact factor: 9.261
Authors: Lisa Mirabello; Roelof Koster; Branden S Moriarity; Logan G Spector; Paul S Meltzer; Joy Gary; Mitchell J Machiela; Nathan Pankratz; Orestis A Panagiotou; David Largaespada; Zhaoming Wang; Julie M Gastier-Foster; Richard Gorlick; Chand Khanna; Silvia Regina Caminada de Toledo; Antonio S Petrilli; Ana Patiño-Garcia; Luis Sierrasesúmaga; Fernando Lecanda; Irene L Andrulis; Jay S Wunder; Nalan Gokgoz; Massimo Serra; Claudia Hattinger; Piero Picci; Katia Scotlandi; Adrienne M Flanagan; Roberto Tirabosco; Maria Fernanda Amary; Dina Halai; Mandy L Ballinger; David M Thomas; Sean Davis; Donald A Barkauskas; Neyssa Marina; Lee Helman; George M Otto; Kelsie L Becklin; Natalie K Wolf; Madison T Weg; Margaret Tucker; Sholom Wacholder; Joseph F Fraumeni; Neil E Caporaso; Joseph F Boland; Belynda D Hicks; Aurelie Vogt; Laurie Burdett; Meredith Yeager; Robert N Hoover; Stephen J Chanock; Sharon A Savage Journal: Cancer Discov Date: 2015-06-17 Impact factor: 39.397