Karsten Schluens

The global gene expression profiles for 67 human lung tumors representing 56 patients were examined by using 24,000-element cDNA microarrays. Subdivision of the tumors based on gene expression patterns faithfully recapitulated morphological classification of the tumors into squamous, large cell, small cell, and adenocarcinoma. The gene expression patterns made possible the subclassification of adenocarcinoma into subgroups that correlated with the degree of tumor differentiation as well as patient survival. Gene expression analysis thus promises to extend and refine standard pathologic analysis.

Object The authors investigated the spectrum of chromosomal imbalances of pilocytic astrocytoma by using comparative genomic hybridization (CGH). Methods Tumor DNA was extracted from surgically obtained samples of 18 pilocytic astrocytomas that were examined for the presence of neoplastic tissue on frozen sections. Comparative genomic hybridization was performed using standard procedures, and digital image analysis was conducted using out by custom-made software. The chromosomal alterations were determined by a statistical procedure in which Student's t-test (99% confidence interval) was used. Details on CGH analysis and individual ratio profiles are available at http://amba.charite.de/cgh/ . Conclusions The results suggests the presence of two distinct genetic subgroups of pilocytic astrocytoma, with imbalances of chromosome 19 being the major change for differentiation. In the first group (10 samples), deletions on chromosome 19 were shown as well as multiple gains mainly on chromosomes 5 and 6q but also on chromosomes 4, 7, 8, 10, and 11. The second group (eight samples) was characterized by overrepresentation on chromosomes 19p and 22q, which were associated with deletions on 4q, 5q, 6q, 9p, 13q, and 18q. To understand the diverse biological and clinical behavior exhibited by this tumor type, it is important that pilocytic astrocytomas be classified into distinct subgroups according to their genetic makeup.

BACKGROUND: To investigate the relationship of p63 expression and p63 locus at chromosomal 3q27-q29 in non-small cell lung cancer (NSCLC). METHODS: Chromosomal imbalance in 30 cases of squamous cell carcinoma (SCC) and 40 cases of adenocarcinoma of the lung were evaluated by comparative genomic hybridization (CGH) technology. A tissue microarray of specimens from 122 primary NSCLC specimens was employed and used for immunohistochemical detection of p63 protein expression. RESULTS: p63 positivity was found in 54 (44.26%) cases of NSCLC. p63 immunostaining was observed in 51 (86.44%) of 59 SCC, whereas only one adenocarcinoma (1.67%) showed immunoreactivity. Immunopositivity was seen in 2 (66.66%) of 3 large cell lung cancer (LCLC). No correlation existed between p63 protein expression and the age of patient, sex, tumor grading, tumor metastasis, prognosis (P > 0.05). The CGH results revealed that the gain of chromosome 3q27-q29 was identified in 32 (48.57%) of 70 NSCLC samples tested. Overrepresentation was detected in 24 cases of 30 SCC. In 40 adenocarcinoma, only 8 cases showed chromosome gain at chromosomal 3q27-q29. The comparison of p63 immunostaining with chromosomal alteration of 3q27-q29 demonstrated that pronounced gain was detected in 23 (95.83%) cases of 24 SCC with p63 immunopositivity. One case of adenocarcinoma that was p63 positive showed a chromosomal 3q27-q29 normal representation but not pronounced gain. CONCLUSIONS: The results suggest that p63 immuno-positivity correlates significantly with pronounced gains of the p63 locus at chromosomal 3q27-q29, and p63 gene amplification correlates with development and progression of lung SCC.

Non-functioning pituitary adenomas have no hormone immunoreactivity, and no other immunohistochemical or ultrastructural markers of specific adenohypophysial cell differentiation. Because only few studies describe cytogenetic changes in non-functioning pituitary adenomas, we studied the spectrum of chromosomal imbalances associated, using comparative genomic hybridization (CGH). Copy number aberrations on all 22 autosomes were evaluated by CGH using advanced computer software. In total, ten patients with non-functioning pituitary adenomas were included in the study. Average sum of imbalances in this group was 22.7±11.8. Average number of gains was 8,0±7.8 whereas number of losses was 14.7±10.1. The typical changes of this group were losses of chromosomes 5q, 14q, 4q, 6q and gains on chromosome 9q. The histogram indicated the highest frequency of changes for the losses were on –5q22–3, -14q31 (7/10) –4q21, -4q24, -4q24–6, -6q14 (6/10) and for gains +9q21 (6/10). Average number of changes in nonfunctioning adenomas was lower than in functioning once. Our analysis of chromosome abnormalities in non-functioning pituitary adenoma will contribute to our knowledge of this group of neoplasm.