Elevated p53 expression in benign meningiomas protects against recurrence and may be indicative of senescence.
Prediction of recurrence after resection of benign meningiomas represents a significant clinical problem. A prospective study commenced in 1984 aimed to elucidate the molecular mechanisms involved in the development of abnormal karyotype and tumour recurrence in meningiomas. Expression of key cell cycle regulators p53, p21, mdm2 and proliferating cell nuclear antigen (PCNA) were studied by immunohistochemistry in 85 tumours for which follow-up data was available. It was found that most tumours expressed p53, p21 and PCNA, with significant correlations between expression of p53 and both p21 and PCNA. As PCNA fulfils a multifunctional role its expression may be an unreliable indicator of proliferation in benign tumours. The degree of tumour excision remains the best prognostic indicator while p53 is the main predictor of abnormal karyotype. Karyotype is not however, related to prognosis. Incompletely excised tumours which expressed high levels of p53 and p21 did not recur. It is suggested that this is indicative of a fully functional p53-mediated DNA damage response mechanism. Rather than contributing to tumour progression, p53 is fulfilling its role as guardian of the genome in benign meningiomas. This study shows that induction of senescence may be an important tumour suppressor mechanism in benign tumours.
Hakin-Smith
V
V
Institute for Cancer Studies, Department of Clinical Oncology and Cellular Pathology, University of Sheffield Medical School, Sheffield, UK.
Battersby
R D
RD
Maltby
E L
EL
Timperley
W R
WR
Royds
J A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008577:Meningeal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009687:Nuclear Proteins; D011237:Predictive Value of Tests; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051736:Proto-Oncogene Proteins c-mdm2; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2