Early recurrences in histologically benign/grade I meningiomas are associated with large tumors and coexistence of monosomy 14 and del(1p36) in the ancestral tumor cell clone

Abstract

Tumor recurrence is the major clinical complication in meningiomas, and its prediction in histologically benign/grade I tumors remains a challenge. In this study, we analyzed the prognostic value of specific chromosomal abnormalities and the genetic heterogeneity of the tumor, together with other clinicobiological disease features, for predicting early relapses in histologically benign/grade I meningiomas. A total of 149 consecutive histologically benign/grade I meningiomas in patients who underwent complete tumor resection were prospectively analyzed. Using interphase fluorescence in situ hybridization, we studied the prognostic impact of the abnormalities detected for 11 different chromosomes, together with other relevant clinicobiological and histopathological characteristics of the disease, on recurrence-free survival (RFS) at 2.5, 5, and 10 years. From the prognostic point of view, losses of chromosomes 9, 10, 14, and 18 and del(1p36) were associated with a shorter RFS at 2.5, 5, and 10 years. Similarly, histologically benign/grade I meningiomas showing coexistence of monosomy 14 and del(1p36) in the ancestral tumor cell clone displayed a higher frequency of early relapses. In fact, coexistence of -14 and del(1p36) in the ancestral tumor cell clone, together with tumor size, represented the best combination of independent prognostic factors for the identification of those patients with a high risk of an early relapse. Our results indicate that patients with large histologically benign/grade I meningiomas carrying monosomy 14 and del(1p36) in their ancestral tumor cell clone have a high probability of relapsing early after diagnostic surgery. These findings suggest the need for closer follow-up in this small group of patients.

A review of epigenetic and gene expression alterations associated with intracranial meningiomas

“…2 There is no clear explanation, however, as to why the majority of recurrent meningiomas derive from benign histology even after apparently radical removal. 55 Other attempts to classify meningiomas have used genomic techniques to study their genesis and progres sion, 73 as well as to search for genetic mutations and variable gene expression mediated via epigenetic modi fications. 35 The use of epigenomics as a clinical tool has become better understood in recent years 47 and research has started to elucidate the importance of epigenetics in meningioma progression.…”

Array-based comparative genomic hybridization of mapped BAC DNA clones to screen for chromosome 14 copy number abnormalities in meningiomas

“…Recently, we have shown that meningioma patients with monosomy 14 and del(1p36), together with a larger tumour size, have a higher probability of relapsing during the first 2.5 years after diagnostic surgery. 10 Interestingly, in our study, all except two cases with the complete loss of chromosome 14 also displayed del(1p36) in the ancestral tumour cell clone (Table 1) and these latter patients included the two cases who had relapsed. Previous studies 1,11,36 have defined a few regions (eg, 14q24.3-q32.33 and 14q11.2) as critical regions in chromosome 14 where candidate genes involved in determining the clinical behaviour of meningiomas could be localized.…”

“…From the clinical point of view, chromosome 14 loss has been associated with a shorter recurrence-free survival, independently of tumour histopathology, particularly when detected in all tumour cells in the sample (eg, in the ancestral tumour cell clone) in association with del(1p36). 3,9,10,25 Altogether, these results suggest the presence of one or more tumour suppressor genes in this chromosome. Despite this, few studies have been reported so far in which a more precise characterization of the genetic changes involving chromosome 14, aimed at a better understanding of the clinical behaviour of the tumour, have been analysed.…”

“…Twelve of the 25 samples used in this study had been also included in a previous report. 10 All tumour samples but one corresponded to primary tumours; the other sample was from a recurrent meningioma. In all patients, diagnosis and classification of meningioma were performed according to the WHO criteria.…”

New automated image analysis method for the assessment of Ki-67 labeling index in meningiomas.

“…Many studies confirmed the importance of tumour localisation, proliferative markers like Ki-67, the type of tumour resection and also the specific genetic alterations, for the risk of neoplasm recurrences [1,6,17,18].…”