Abstract
to determine the expression of neurotrophins and their tyrosine-kinase receptors in patients with osteosarcoma (OS) and their correlation with clinical outcomes. we applied immunohistochemistry to biopsy specimens of patients consecutively treated for primary OS at a single institution between 2002 and 2015, analyzing them for expression receptors of tyrosine kinase A and B (TrKA and TrKB), neural growth factor (NGF) and brain derived neurotrophic factor (BDNF). Independently, two pathologists classified the immunohistochemical markers as negative (negative or weak focal) or positive (moderate focal/diffuse or strong focal/diffuse). we analyzed data from 19 patients (10 females and 9 males), with median age of 12 years (5 to 17.3). Tumors' location were 83.3% in the lower limbs, and 63.2% of patients had metastases at diagnosis. Five-year overall survival was 55.3%. BDNF was positive in 16 patients (84%) and NGF in 14 (73%). TrKA and TrKB presented positive staining in four (21,1%) and eight (42,1%) patients, respectively. Survival analysis showed no significant difference between TrK receptors and neurotrophins. primary OS samples express neurotrophins and TrK receptors by immunohistochemistry. Future studies should explore their role in OS pathogenesis and determine their prognostic significance in larger cohorts.
Highlights
Osteosarcoma (OS) is a malignant bone tumor found preferentially in individuals between ten and 25 years old
Out of 28 patients treated for OS in the Service, we excluded four due to insufficient or unavailable sample to perform the immunohistochemical study, and five that did not undergo the Brazilian Osteosarcoma Treatment Group (BOTG) V and GCBTO 2006 protocol
Combinations of TrkA-neural growth factor (NGF)-positive, TrkA-NGF negative, Trk B receptor (TrkB)-brain derived neurotrophic factor (BDNF)-positive and TrkBBDNF-negative were not significantly associated with survival. This is the first study evaluating the expression of neurotrophins and their TrK receptors in primary OS tumors in humans
Summary
Osteosarcoma (OS) is a malignant bone tumor found preferentially in individuals between ten and 25 years old. Up to 30% of patients have metastases, considered the main prognostic factor. The development of chemotherapy at high doses increased survival considerably. Since the early 2000s, this therapeutic option has reached its plateau. There was no significant progress in OS treatment during this period[1,2,3,4,5,6]. The search for therapies based on the molecular profile of the tumor has grown considerably[7]
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