RESUMO
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.
RESUMO
Pituitary adenomas most commonly are identified as small, incidental microadenomas. They however may progress to macroadenoma forming intra and later suprasellar tumors which in about 1/3 of cases invade surrounding structures at the time of diagnosis. Mechanism of pituitary tumorigenesis remains still elusive. Because the value of karyotyping is limited by the technical problems related to cytogenetic methods, we studied the spectrum of chromosomal imbalances associated with pituitary adenoma using comparative genomic hybridization (CGH). Copy number aberrations on all 22 autosomes were evaluated by CGH using advanced computer software. In total, fifteen patients were included in the study of 9 non-invasive, 4 invasive and two recurrent adenomas. The mean age of the patients were 48 years ranging from 36 to 68 years. Five tumors showed hormonal activity. The histogram of all 15 cases representing the DNA imbalances as an incidence curve along each chromosome showed losses particularly for chromosomes 1p, 2q, 4, 5, 6, 11q, 12q, 13q and 18q as well as overrepresentation on 9q, 16p, 17p, 19, 20q. Functioning adenomas carried more imbalances than non-functioning, specifically deletions on chromosome 4 and 18q as well as overrepresentations of chromosomes 17 and 19. Invasive adenomas carried more overrepresentations at 1p34 than non-invasive tumors. Recurrent adenomas harbored more alterations than primary tumors, particularly DNA gains. The primary data is accessible at our CGH online tumor database at http://amba.charite.de/cgh. Reviewing the existing literature on the genetics of pituitary adenoma and discussing our results in this context, we hope that our study will contribute to the knowledge of this neoplasm.