Polysomy for chromosomes 1 and 19 predicts earlier recurrence in anaplastic oligodendrogliomas with concurrent 1p/19q loss

Abstract

Purpose: Loss of chromosome arms 1p and 19q is a molecular feature of oligodendroglial tumors characterized by responsiveness to chemotherapy and a favorable prognosis. The purpose of this study was to evaluate the prognostic significance of polysomy of chromosomes 1 and 19 in the setting of 1p/19q codeletion.

Experimental design: We analyzed 64 anaplastic oligodendrogliomas with 1p/19q loss or maintenance diagnosed at Massachusetts General Hospital and Brigham and Women's Hospital from 1996 to 2005; fluorescence in situ hybridization for 1p/19q and Ki-67 immunohistochemistry was done. Polysomy was defined as more than two 1q and 19p signals in >30% of the cells with concurrent 1p/19q deletion. Tumors were divided into groups based on their 1p/19q status and compared for progression-free survival, overall survival, and 5-year survival probabilities.

Results: Forty-six tumors (72%) in our cohort had 1p/19q loss and 18 (28%) had 1p/19q maintenance. Of those with loss, 19 (41%) had concurrent polysomy and 27 (59%) lacked polysomy. In agreement with previous studies, the group of anaplastic oligodendrogliomas with 1p/19q loss had significantly better progression-free survival and overall survival than anaplastic oligodendrogliomas with 1p/19q maintenance (P = 0.0009 and P < 0.0003, respectively). Among anaplastic oligodendrogliomas with 1p/19q loss, those with polysomy showed shorter progression-free survival than those with 1p/19q loss without polysomy (P = 0.0048). Overall survival was similar in tumors with and without polysomy. The Ki-67 labeling index was not associated with polysomy and did not have prognostic significance.

Conclusion: The presence of polysomy in anaplastic oligodendrogliomas with deletion of 1p/19q is a marker of earlier recurrence.

Figure 1

Representative FISH figures for chromosome 1 probes illustrating 1p maintenance (A), 1p loss (B) and 1p loss with concurrent polysomy (C). H&E sections of anaplastic oligodendroglioma with 1p/19q loss only (D) and 1p/19q loss and polysomy (F). Ki-67 proliferation activity was similar in AO with 1p/19q loss only (E) and 1p/19q loss with polysomy (G). Scale bar represents 150 μm.

Figure 2

1- AO with 1p/19q maintenance; 2- 1p/19q loss, all cases; 3- 1p/19q loss and polysomy; 4- 1p/19q loss without polysomy; In the entire cohort of 64 patients, 1p/19q maintenance is associated with decreased progression free survival (1A; p = 0.009) as well as overall survival (1B; p < 0.0003) when compared to anaplastic oligodendrogliomas with 1p/19q loss. Anaplastic oligodendrogliomas with 1p/19q loss and polysomy have significantly worse progression free survival than AO with 1p/19q loss without polysomy (1C, p=0.0048). Difference in PFS between AO with 1p/19q maintenance and 1p/19q loss with polysomy was not significant (1C; p=0.303) while the overall survival of AO with 1p/19q loss and polysomy was significantly better than AO with 1p/19q maintenance (1D; p=0.0172). The difference in OS between 1p/19q co-deleted AO with and without polysomy was not significant (1D; p=0.303). All p-values are multiplied by 3 to adjust for multiple testing.