Clinical and Pathologic Relevance of p53 Index in Canine Osseous Tumors

Abstract

The clinicopathologic value of the immunohistochemical (IHC) expression of p53 protein was evaluated in 167 canine osseous tumors. p53 staining frequency and intensity in tumor cells was expressed as a p53 index. p53 index was significantly higher in osteosarcomas than in other sarcomas, chondrosarcoma, multilobular tumor of bone, and tumors initially misdiagnosed as osteosarcomas as well as in appendicular versus axial and in distal versus proximal osteosarcomas. A strong correlation is demonstrated between the p53 index and a range of clinicopathologic parameters in osteosarcoma, including the tumor site, histologic grade and score, mitotic index, degree of tumor necrosis, and pleomorphism. Chondroblastic osteosarcomas had significantly higher and telangiectatic osteosarcomas significantly lower p53 index than did osteosarcomas belonging to other histopathologic subtypes, a fact that tends to reinforce the perception of these osteosarcomas as distinct clinicopathologic entities. Entire males had higher p53 index than did neutered males. p53 index was higher in Rottweilers than in Great Danes and Terriers, confirming breed susceptibilities to osteosarcoma. p53 index showed no association with age, primary or secondary site status, or the presence of metastases or other tumor types. Biopsy samples had a higher p53 index than did postmortem samples, either because of differences in sample processing or the possibility that p53 overexpression is more evident at the earlier stages of osteosarcoma pathogenesis, presumably represented by the biopsy material. IHC examination for p53 and the derived index has the potential to be used as an additional diagnostic tool and prognostic indicator for osseous tumors.

Immunohistochemical expression of dogTERT in canine testicular tumours in relation to PCNA, ki67 and p53 expression.

“…The fact that higher levels of mutated p53 were detected in more aggressive tumour types in our study is in agreement with reports on most other neoplasms in man and domestic animals in which increased p53 expression is considered as an index of aggressiveness and metastatic status and consequently as a prognostic marker (Iggo et al 1990;Vitellozzi et al 1998;Cadwell and Zambetti, 2001;Loukopoulos et al 2003). Tumours exhibiting solely cytoplasmic p53 immunoreactivity have been classified as p53 negative in previous studies (Loukopoulos et al 2003). Our results also showed p53 immunopositivity in 50% of SCTs, a fact in agreement with a report by Inoue and Wada (2000) that showed the same immunoreactivity patterns in seminomas and SCT.…”

“…All granular stained nuclei were considered as positive for ki67. p53 immunostaining was considered as positive only if nuclear staining was clearly detected; cytoplasmic staining alone was not recorded as positive (Inoue and Wada 2000;Loukopoulos et al 2003). The following scoring system was applied: score 0, (-): (0-10% positive cells); score 1, (+): (11-30% positive cells); score 2, (++): (31-50% positive cells); score 3, (+++): (>50% positive cells).…”

Anti-Tumor Effect of Adenoviral Vector-Mediated p53 Gene Transfer on the Growth of Canine Osteosarcoma Xenografts in Nude Mice

“…If the P53 protein is inactivated, the cell cycle and apoptotic pathways can be impaired. Immunohistochemical studies revealed an accumulation of aberrant P53 expression in a high proportion of osteosarcomas in dogs [16,25], and mutations of p53 were also found in a significant number of canine osteosarcomas [11,13,20,26,31]. These results indicate that inactivation of the p53 tumor suppressor gene is a frequent genetic event found in canine osteosarcoma.…”

Multilobular tumour of the caudal cranium causing severe cerebral and cerebellar compression in a dog

“…Most bone tumours are osteosarcomas, and MTBs may be misdiagnosed as such [10]; however MTB must also be differentiated from other primary bone tumours, particularly chondrosarcoma [6,10]. Other, non- neoplastic causes of neurological signs associated with cerebral and cerebellar dysfunction should be ruled out in these cases, employing, when feasible, advanced diagnostic imaging or other techniques.…”