Interphase cytogenetics for 1p19q and t(1;19)(q10;p10) may distinguish prognostically relevant subgroups in extraventricular neurocytoma

Abstract

Co-deletion of chromosome arms 1p and 19q, characteristic of oligodendroglial tumors, was recently found to be mediated by t(1;19)(q10;p10). To evaluate the prevalence of 1p19q co-deletion and t(1;19) in extraventricular neurocytomas (EVN), we studied tumors from 23 patients, including 13 females and 10 males (median age at diagnosis 34 years, range 2-76 years). Fluorescence in situ hybridization (FISH) studies were performed with probes targeting 1p36/1q25 and 19q13/19p13 to assess for 1p19q co-deletion, as well as chromosome 1 alpha-satellite and 19p12 to detect t(1;19)(q10;p10). FISH was successful in 21 (91%) cases and demonstrated 1p19q co-deletion in five cases (24%) or isolated 1p loss in two cases (10%). Evidence for t(1;19) was found in four (of five) cases with 1p19q co-deletion. Three tumors with 1p19q loss and t(1;19) demonstrated atypical histologic features, compared with one (of 17) tumors without 1p19q co-deletion (P = 0.01, Fisher exact test). In addition, tumors with t(1;19) showed increased mitotic activity compared with tumors without t(1;19) (P = 0.045; Wilcoxon rank sum test). The four patients with t(1;19) developed tumor recurrence (n = 3), or expired (n = 2) 3.5 to 5.5 years after first resection. These results suggest that 1p19q loss and t(1;19) occur in a subset of EVN, and may be associated with aggressive histology in these tumors.

Figure 1

Histologic features of extraventricular neurocytoma (Case 8). Morphologic features of neuronal differentiation were evident on hematoxylin–eosin stain (A,B), including extensive neuropil formation and neurocytic cytology. Immunohistochemical stains for synaptophysin labels individual cells and neuropil (C). Neu‐N stain was positive in a nuclear fashion in all cases tested (D). Electron microscopy demonstrating dense core secretory granules (E).

Figure 2

t(1;19) and 1p loss coexist in the same cells (Case 4). Three‐color fluorescence in situ hybridization strategy demonstrates a red/green fusion and a single aqua signal representing t(1;19) and 1p loss in the same cells, respectively (left). The same tumor also demonstrates a single red signal and two green signals in most cells reflecting 19q loss (right).

Figure 3

1p19q loss reflecting genetic heterogeneity (Case 1). The pattern of 1p19q loss in this case was unique, as it was limited to separate geographic areas (hematoxylin–eosin stain) (A). Dual‐color fluorescence in situ hybridization studies demonstrate a normal chromosome 1 (B) but 19q loss in most areas (C). Relative 1p loss with aneusomy (D) was a focal finding in an area showing no abnormalities in chromosome 19 (E). t(1;19) was absent (not shown).

Figure 4

Fluorescence in situ hybridization studies identify two distinct subgroups in EVN. Scatterplot demonstrates increased mitoses per 10 high‐power fields in extraventricular neurocytomas (EVN) with 1p19 co‐deletion and t(1;19) as compared with EVN without 1p19q loss and t(1;19) (P = 0.045, Wilcoxon rank sum test).