title: The use of Bcl-2 and PTHLH immunohistochemistry in the diagnosis of peripheral chondrosarcoma in a clinicopathological setting.
abstract: Distinguishing osteochondroma from low-grade secondary peripheral chondrosarcoma can be difficult. In osteochondroma, growth-signalling pathways are thought to be downregulated through exostosin (EXT) inactivation. A previous pilot study focusing on expression of putative EXT downstream effectors indicated that progression of osteochondroma towards grade I chondrosarcoma was characterised by upregulation of Bcl-2 and parathyroid hormone-like hormone (PTHLH). We investigated their use as diagnostic markers in a large nationwide series of 71 osteochondromas and 34 chondrosarcomas. Bcl-2 immunohistochemistry proved to be a valuable diagnostic tool: scoring negative in 95% (specificity) of the osteochondromas and positive in 57% (sensitivity) of the chondrosarcomas, reaching a positive predictive value of 84% and negative predictive value of 82%. Positivity was not related to age, hereditary status, gender or thickness of the cartilage cap. Presence of internal controls and verification using mRNA in situ hybridisation strengthened the reliability of the immunohistochemical staining. PTHLH showed more variable staining, being positive in osteochondromas from females or adolescent males, suggesting age- and gender-dependent expression. Thus, in cases where the distinction between osteochondroma and chondrosarcoma is difficult, Bcl-2 is a valuable diagnostic marker for malignancy, regardless of tumour size, patient gender or age, and this can be extended with PTHLH for non-adolescent male patients.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, L1-Q, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Hameetman
authors.forename: Petra
authors.initials: P
authors.lastname: Kok
authors.forename: Paul H C
authors.initials: PH
authors.lastname: Eilers
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Judith V M G
authors.initials: JV
authors.lastname: Bovée
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D018211:Chondrosarcoma, Mesenchymal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D015831:Osteochondroma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity; D012737:Sex Factors
chemical_list: D014408:Biomarkers, Tumor; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger
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