👤 T Böhling

Hemangioblastoma is a highly vascularized, benign tumor in the central nervous system, frequently associated with von Hippel-Lindau (VHL) disease. Hemangioblastoma may cause tumor-associated hemorrhage or exert pressure on nearby structures, leading to life-threatening complications. Although surgical resection is the primary treatment, complete removal is not always feasible. Accordingly, there is a need to explore targeted or anti-angiogenic therapies. The fibroblast growth factor receptor (FGFR) family has roles in tumorigenesis and angiogenesis, making it a potential target in personalized therapy. The distribution and significance of FGFRs in hemangioblastoma have yet to be investigated. We examined 139 formalin-fixed, paraffin-embedded hemangioblastoma samples from 111 patients, including sporadic cases and those associated with VHL disease. Immunohistochemistry revealed positive staining for FGFR2 (95%) and FGFR4 (61%), while FGFR1 (0%) and FGFR3 (12%) were mainly negative. FGFR2 expression was significantly increased in VHL-mutated tumors (75%, p = 0.034) and in male patients (68%, p = 0.020). Tumors located in the cerebrum (n = 6, 5%) had a higher likelihood of positive FGFR4 staining (100%, p = 0.009). Additionally, a larger tumor diameter was associated with a higher likelihood of FGFR4 expression (median 12.0 mm vs 17.5 mm, p = 0.018), suggesting its contribution in tumor growth. Our study revealed the expression of FGFR2 and FGFR4 in a significant number of hemangioblastomas. This finding demonstrates the potential of FGFRs as promising therapeutic targets for patients with hemangioblastoma. Show less

Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP did not affect CDKN2A. Deletions were also found to affect genes of the cadherin family, including CDH4 and CDH7, each of which had a targeted homozygous loss in one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or EXT2 were seen in three cases. Targeted gains and amplifications affected the MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate that chondrosarcomas develop through a combination of genomic imbalances that often affect the RB1 signaling pathway. The inactivation of cadherin genes may also be critical in the pathogenesis of the tumor. Show less

Multiple hereditary exostoses is an autosomal dominant skeletal disorder in which there are numerous cartilage-capped excrescences in areas of actively growing bone. The condition is genetically heterogeneous, and at least three genes, ext1, ext2 and ext3 are involved. The reported risk for malignant transformation to chondrosarcoma has been from 0.6% to 2.8%. We have reviewed six generations of a family with 114 living adult members, 46 of them with multiple exostoses. Four have had operations for chondrosarcoma, giving the risk for malignant transformation as 8.3% in this family. Clinical and radiological examination revealed two additional patients with a suspicion of malignancy, but in whom the histological findings were benign. Reported elsewhere in detail, genetic linkage analysis mapped the causative gene to chromosome 11 and molecular studies revealed a guanine-to-thymine transversion in the ext2 gene. Patients with multiple hereditary exostoses carry a relatively high risk of malignant transformation. They should be informed of this possibility and regularly reviewed. Show less