Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma

Abstract

The overall incidence of osteosarcoma is low. However, the occurrence of osteosarcoma in a setting of multiple primary tumours is not infrequent, although population-based incidence numbers are unknown. The occurrence of osteosarcoma and other malignancies is frequently related to treatment, and can also be the result of genetic predisposition as in patients with retinoblastoma, Li-Fraumeni syndrome, Werner syndrome and Rothmund-Thomson syndrome. The aim of our study is to establish the incidence of osteosarcoma associated with other malignancies in a populationwide study and to find out if these osteosarcomas have a specific subtype, that could draw attention to a genetic predisposition to malignancy. A list of all patients registered in the Dutch National Pathology Register, named PALGA, with a diagnosis of osteosarcoma between 1975 and May 2000 was retrieved. All patients with another malignancy besides osteosarcoma were selected. All patients registered in the same period with a tonsillectomy served as a control for the occurrence of malignancy in a normal population. In a second step, only osteosarcoma patients with a history of retinoblastoma or a malignancy before the age of 46 years, since these are most probable to have a hereditary cancer syndrome, were retained for further analysis. The osteosarcomas were subtyped as common, chondroblastic, fibroblastic, teleangiectatic, anaplastic, osteoclast-rich or small cell. As a control for osteosarcoma subtypes the data of 570 patients entered in two studies from the European Osteosarcoma Intergroup (EORTC/MRC) were used. Of all 938 patients registered with the diagnosis of osteosarcoma, 66 had a history of multiple primary tumours. Four patients had a surface osteosarcoma, three an extraskeletal osteosarcoma and 59 had intramedullar highgrade osteosarcoma. Of this last group, one patient was known with Rothmund -Thomson syndrome, one had retinoblastoma and 30 had their malignancies before the age of 46. Of these 32 patients, 17 had osteosarcoma of the long bones. Especially women seem to be more susceptible for the development of multiple primaries. In nine patients, the histological subtype could be assessed by revision of available histological slides. All of these patients had an osteosarcoma subtype other than common as opposed to 29% in the control group of the European Osteosarcoma Intergroup. It is concluded that although the www.nature.com/ejhg incidence of osteosarcoma is low, the occurrence of another malignancy in osteosarcoma patients is higher than in the normal population. Specifically, osteosarcoma patients have a relative risk of 2.4 (95% confidence interval 1.88 -3.07) to develop another malignancy. A noncommon subtype of osteosarcoma should draw attention to a possible genetic predisposition of the patient involved.

The Werner syndrome protein has separable recombination and survival functions☆

“…One place to look for such selective WRN functional deficits in association with WRN missense mutations or polymorphisms is in otherwise normal individuals who have multiple primary neoplasms of the types observed in WS patients, e.g. osteosarcoma [36,37]. If identified, additional WRN-linked recombination deficiency syndromes would join WS and a growing number of human disease predispositions that result from defects in recombination pathways that act to insure genomic stability and suppress the risk of cancer [38,39].…”

The Synergistic Anticancer Effect of Artesunate Combined with Allicin in Osteosarcoma Cell Line in Vitro and in Vivo

“…Osteosarcoma is one of the most common malignant bone tumors in children and adolescents (Meyers et al, 1998;Bacci et al, 2000;Hauben et al, 2003;Chano et al, 2004;Marina et al, 2004;Benassi et al, 2007). The present therapeutic strategies in clinical applications have low efficiency under the current osteosarcoma therapy (Huang et al, 2012;Choeyprasert et al, 2013).…”

Microarray analysis identifies distinct gene expression profiles associated with histological subtype in human osteosarcoma

“…Previous studies have shown that the histological subtype of osteosarcoma is a predictive factor for response to chemotherapy [7,8] and correlates with disease-free [9,10] and overall survival [3]. Furthermore, a non-common subtype of osteosarcoma raises the possibility of an individual belonging to a family with hereditary cancer syndrome, reflecting a possible genetic background for malignancy [11]. So far the treatment options for most patients with osteosarcoma are not different between either of these histological subtypes.…”