Journal of Neuro-Oncology 00: 1–9, 2004. © 2004 Kluwer Academic Publishers. Printed in the Netherlands. Laboratory Investigation Deletions of chromosomes 1p and 19q are detectable on frozen smears of gliomas by FISH: usefulness for stereotactic biopsies Corinne Bouvier 1,∗ , Patrice Roll 2,∗ , Benoit Quilichini 2 , Philippe Metellus 3 , Arlette Calisti 1 , Sophie Gilles 4 , Olivier Chinot 4 , Frederic Fina 4 , Pierre M. Martin 4 and Dominique Figarella-Branger 1 1 Laboratoire de Biopathologie Nerveuse et Musculaire, EA 3281, Facult´ e de M´ edecine, 27 bd Jean Moulin, 13005 Marseille, France; 2 Service de cytog´ en´ etique oncologique, 3 Service de Neurochirurgie, CHU Timone, rue Saint Pierre, 13005 Marseille, France; 4 Laboratoire de transfert d’Oncologie Biologique, IFR Jean Roche, Bd Pierre Dramard, 13916 Marseille, France Key words: FISH, LOH, smears, stereotactic biopsy, 1p/19q Summary Among diffuse gliomas, oligodendrogliomas may account for 25% of cases. They have a better prognosis and chemosensitivity as compared to astrocytomas. Genetic studies have shown a correlation between oligodendrocyte phenotype and presence of 1p/19q deletions. In addition, these deletions are of prognostic value. The aim of the present study was to describe a new method to detect 1p/19q deletions when little tumoral material is available (stereotactic biopsies (SBs)). Since smears (cytological preparations) are routinely done for intraoperative diagnosis of gliomas, we have searched for 1p/19q deletions by FISH in a series of 30 patients with a glioma. In 14 cases, loss of heterozygosity (LOH) analysis was also performed in order to validate our method. We found that FISH analysis on frozen smears was a simple, rapid and reliable method to detect 1p/19q deletions and a good concordance was found with LOH data (85%). The main advantages of FISH analysis on frozen smears are the following. First, it requires little material and can be easily done in the case of SBs. Second, it has a higher sensitivity than LOH especially in infiltrative areas of gliomas. Third, it allows detection of a codeletion 1p/19q in a single tumor cell. In contrast, LOH analysis is easier to interpret and can detect smaller and partial deletion whose pronostic significance remains to be defined. In conclusion, these two techniques can be used to investigate 1p/19q status in gliomas. The appropriate choice of one or other of these two techniques will depend on the specific questions that need to be answered. Introduction Diffuse gliomas are the most frequent primary central nervous system tumors. Among them, oligodendro- gliomas may represent up to 18% of cases [1]. They have a better prognosis and chemosensitivity than the astrocytomas. Unfortunately, the histological classifi- cation scheme remains somewhat subjective, leading to considerable interobserver variability for glioma diagnosis [2]. Genetic studies have shown that up to 50–80% of oligodendrogliomas harbor deletions usually involving the whole chromosome 1p and 19q arms [3–10]. The correlation between oligodendrocyte ∗ These authors have contributed equally to this work. phenotype and genetic profile is even higher (93%) if only oligodendrogliomas with ‘chicken wire pattern’ of vessels and ‘clear perinuclear halo’ are taken into account [11]. Deletions of chromosomes 1p and 19q are also of pronostic value since the genetic subset of oligodendrogliomas which harbors this abnormality has a better prognosis and chemosensitivity to PCV [12,13]. Recently, 1p/19q codeletion was found to be an independent pronostic factor for overall survival in multivariate analysis for grade III oligodendrogliomas [14]. Codeletion was also predictive of a marked and durable response to chemotherapy [14] and of a longer progression-free survival [15]. So, among genetic markers, 1p/19q status could be an aid for therapeutic decisions. Deletions could be searched by FISH or NEON6RI (BIO2FAM) PIPS 5270318 CP DISK pp. 1–9 ☛ ✡ ✟ ✠ UNCORRECTED PROOF