ABSTRACT
Phosphatase and tensin homolog (PTEN) is a critical tumor suppressor gene with a vital role in regulating cell proliferation, migration, and survival. The loss of PTEN function, either by genetic alterations or decreased protein expression, is frequent in human gliomas and has been correlated with tumor progression, grade, therapeutic resistance, and decreased overall survival in patients with glioma. While different genetic mutations in PTEN gene have been occasionally reported in canine gliomas, no alterations in protein expression have been reported. This study investigates the immunohistochemical expression of PTEN in canine gliomas to evaluate possible alterations, as those reported in human gliomas. Immunohistochemical PTEN expression and pattern distribution were analyzed in 37 spontaneous canine gliomas. Among gliomas, 52.6% cases showed high PTEN expression and 48.6% displayed reduced (13.5%) or highly reduced (35.1%) immunopositivity. Most oligodendrogliomas showed high expression (73.7%), while the majority of astrocytomas (69.2%) showed a reduced or highly reduced expression. A reduced PTEN expression was mostly associated with a heterogeneous loss of PTEN immunopositivity. These observations are in line with those reported in human gliomas and provide a rationale for future studies regarding abnormalities in PTEN expression and PI3K/Akt/mTor pathway in canine gliomas, to evaluate its prognostic and therapeutic implications.
ABSTRACT
BACKGROUND: A head turn is a clinically relevant abnormality identified on neurological examination and historically has been an isolated or concomitant sign of ipsilateral forebrain dysfunction. Experimental studies in quadrupedal mammals suggest that changes in head posture may be identified as originating in other parts of the central nervous system (CNS). OBJECTIVES: To identify whether other locations within the CNS could give rise to a head turn and whether the head turn identified is isolated or concomitant with other deviations in head and body posture. ANIMALS: Forty-nine client-owned dogs with a presentation of a head turn, from 6 veterinary referral centers. METHODS: Multicenter observational prospective study including dogs with photographic evidence of a head turn, full neurological examination, and advanced imaging. RESULTS: Of the population, 15/49 had head turn only, 9/49 had head turn and head tilt only, 12/49 had head turn and body turn only, and 13/49 had head turn, head tilt, and body turn. Nearly all dogs with forebrain disease (23/24), and, all with brainstem and cerebellar disease, had an ipsilateral head turn and body turn (if present). In the cerebellar group, all head tilts were contralateral to the lesion location. In the cervical spinal cord group, all head turns, body turns and head tilts were contralateral to the lesion location. CONCLUSION: A head turn, although most likely associated with, is not exclusively seen with forebrain disease. Certain combinations of head turn, head tilt and body turn suggest a neurolocalization other than the forebrain, with appropriate classification needed.