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The Cytogenetic Relationship between Primary and Recurrent Meningiomas Points to the Need for New Treatment Strategies in Cases at High Risk of Relapse

Authors' Affiliations: ¹ Unidad de Investigación, ² Neurosurgery Service, and ³ Department of Pathology, Hospital Universitario de Salamanca and ⁴ Centro de Investigación del Cáncer, Cytometry General Service and Department of Medicine, University of Salamanca, Salamanca, Spain

Requests for reprints: Maria Dolores Tabernero Redondo, Hospital Universitario de Salamanca, Laboratorio Unidad de Investigación, Edificio Maternidad 2^a Planta, Paseo de San Vicente 58-182, 37007 Salamanca, Spain. Phone: 34-923-29-12-30; Fax: 34-923-29-46-24; E-mail: taberner{at}usal.es.

Purpose: Recurrence is the major factor influencing the clinical outcome of meningioma patients although the exact relationship between primary and recurrent tumors still needs to be clarified. The aim of the present study is to analyze the cytogenetic relationship between primary and subsequent recurrent meningiomas developed within the same individual.

Experimental Design: Multicolor interphase fluorescence in situ hybridization was done for the identification of numerical abnormalities of 12 chromosomes in single-cell suspensions from 59 tumor samples corresponding to 25 recurrent meningioma patients. In 47 of these tumors, the distribution of different tumor cell clones was also analyzed in paraffin-embedded tissue sections. In parallel, 132 nonrecurrent cases were also studied.

Results: Most recurrent meningiomas showed complex cytogenetic aberrations associated with two or more tumor cell clones in the first tumor analyzed. Interestingly, in most individuals (74%), exactly the same tumor cell clones identified in the initial lesion were also detected in the subsequent recurrent tumor samples. In the recurrent tumor samples of the remaining cases (26%), we observed tumor cell clones related to those detected in the initial lesion but which had acquired one or more additional chromosome aberrations associated with either the emergence of new clones with more complex karyotypes or the disappearance of the most representative clones from the primary lesions. Multivariate analysis of prognostic factors showed that the Maillo et al. prognostic score, based on age of patient, tumor grade, and monosomy 14, together with tumor size was the best combination of independent variables for predicting tumor recurrence at diagnosis.

Conclusion: Overall, our results indicate that the development of recurrent meningiomas after complete tumor resection is usually due to regrowth of the primary tumor and rarely to the emergence of an unrelated meningioma, underlining the need for alternative treatment strategies in cases at high risk of relapse, particularly those with a high Maillo et al. prognostic score and larger tumors.

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