A distinct phenotype characterizes tumors from a putative genetic trait involving chondrosarcoma and breast cancer occurring in the same patient.

Recently, we documented an increased risk for the occurrence of breast- and cartilaginous tumors in the same patient, statistically pointing towards a potential genetic trait. This trait is most probably not associated with mutations in the two major hereditary breast cancer genes since no cases of enchondroma or chondrosarcoma were found in Dutch BRCA1 and BRCA2 families. We were able to collect and review the tumor tissue samples from 34 patients with both breast- and cartilaginous tumors and compared histopathological and immunohistochemical features of these tumors with controls. Breast cancer controls were available from literature data generated to compare familial breast cancers with nonselected cases. Clinical markers for chondrosarcoma controls were collected from the Netherlands Committee of Bone Tumors. Immunohistochemical data on chondro-tumor controls were available from our own files. Breast tumors of patients with cartilaginous sarcomas showed a significantly higher mitotic count (P=0.001), contained less lymphocyte infiltrate (P=0.025) and less nuclear pleomorphism. Remarkably, all cartilaginous tumors are of one common histological category originating centrally (P=0.014). Estrogen receptor and p53 expression were significantly higher (P<0.001) in breast cancer associated with chondro-tumors. p21 staining was more often negative in chondro-tumors associated with breast cancer. In seven cases of breast cancer, we found a slight decrease in CHEK2 expression. However, we could not identify the CHEK2 1100delC mutation in these cases nor in cases with normal CHEK2 expression. Hierarchical cluster analysis of all parameters within chondro-tumor-associated breast cancer specimens revealed two different subgroups, the largest one associated with estrogen receptor-positive breast cancer, which may distinguish sporadic cases from those belonging to the potential genetic trait. These distinct phenotypic findings support the existence of a new hitherto unrecognized syndrome, characterized by an increased risk to develop both breast cancer and centrally originating cartilaginous tumors.