Proliferation and aneusomy predict survival of young patients with astrocytoma grade II.

The clinical course of astrocytoma grade II (AII) is highly variable and not reflected by histological characteristics. As one of the best prognostic factors, higher age identifies rapid progressive A II. For patients over 35 years of age, an aggressive treatment is normally propagated. For patients under 35 years, there is no clear guidance for treatment choices, and therefore also the necessity of histopathological diagnosis is often questioned. We studied the additional prognostic value of the proliferation index and the detection of genetic aberrations for patients with A II. The tumour samples were obtained by stereotactic biopsy or tumour resection and divided into two age groups, that is 18-34 years (n=19) and > or =35 years (n=28). Factors tested included the proliferation (Ki-67) index, and numerical aberrations for chromosomes 1, 7, and 10, as detected by in situ hybridisation (ISH). The results show that age is a prognostic indicator when studied in the total patient group, with patients above 35 years showing a relatively poor prognosis. Increased proliferation index in the presence of aneusomy appears to identify a subgroup of patients with poor prognosis more accurately than predicted by proliferation index alone. We conclude that histologically classified cases of A II comprise a heterogeneous group of tumours with different biological and genetic constitution, which exhibit a highly variable clinical course. Immunostaining for Ki-67 in combination with the detection of aneusomy by ISH allows the identification of a subgroup of patients with rapidly progressive A II. This is an extra argument not to defer stereotactic biopsy in young patients with radiological suspicion of A II.

Differentiation between reactive gliosis and diffuse astrocytoma by in situ hybridization.

The authors examined the use of chromosomal analysis by in situ hybridization to differentiate between nonneoplastic reactive gliosis and astrocytomas in cases in which routine histology was inconclusive. Numerical chromosomal aberrations were found in 80% of low-grade astrocytoma specimens and in none of the reactive gliosis specimens. Aneusomic tumor cells were detected in four of 13 stereotactic samples with an initially inconclusive tissue diagnosis, three of which were later diagnosed as astrocytoma. The in situ hybridization procedure may have additional value in the differential diagnosis of reactive gliosis versus low-grade astrocytoma.

Loss of chromosome 11 and 11 p/q imbalances in bladder cancer detected by fluorescence in situ hybridization.

To identify chromosomal imbalances in non-diploid transitional-cell carcinoma (TCC) of the bladder we performed double-target in situ hybridization (FISH), using the centromeric probe for chromosome 11 together with 2 cosmid probes located on the 11p and 11q arm in the proximity of the telomere. The FISH protocol was optimized to ensure a highly efficient and reproducible detectability of all 3 targets. As a consequence, it was possible to calculate ratios between the number of spots obtained with cosmid and centromere probes. Furthermore, the number of chromosomes 11 present was compared with the DNA index and the chromosome ploidy as obtained with other chromosome centromere probes. In this study we found that: (i) in 54 diploid TCCs a monosomy for chromosome 11 was detected in only one case; (ii) chromosome 11 was completely lost in 9 of 16 non-diploid TCCs; (iii) in 8 of these 16 non-diploid tumors an imbalance was observed between the 11p and 11q arm, in 4 of these cases a complete loss of chromosome 11 being observed in addition; (iv) the copy number counted for 11q was always identical to the 11 centromere number, except in one case, indicating a loss of 11p in the cases with imbalances. In total, 13 of 16 non-diploid TCCs (81%) showed either a loss of a complete chromosome 11, of (part of) the 11p arm, or both. Therefore we concluded that during tetra- or aneuploidization in TCCs, (part of) chromosome 11 is lost. In addition, our results indicate that under-representation of chromosome 11p occurs in the majority of the tumor cells, supporting the idea that loss of these sequences is an important step in the development of TCC.