Alterations of the CCND1 and HER-2/neu (ERBB2) proteins in esophageal and gastric cancers

We evaluated the relationship of amplification and polysomy of both the CCND1 and the ERBB2 (alias HER-2/NEU) genes to the overexpression of their proteins in esophageal and gastric cancers and also their association with clinicopathological features. CCND1 gene amplification (45%) was more prevalent than polysomy (25%) in esophageal carcinoma, but the pattern observed was similar in gastric adenocarcinoma (10% amplification, 15% polysomy). For ERBB2, polysomy was a more frequent mechanism than amplification in both esophageal (32.5 vs. 7.5%) and gastric (15 vs. 5%) cancers. Overexpression of cyclin D1 protein was identified in 37.5% of the specimens of esophageal tumors and 35% of gastric tumors, and overexpression of Her-2/neu protein in 12.5 and 7.5%, respectively. The K-statistics revealed a fair agreement in both types of turners only in overexpression and amplification of the CCND1 ggene; the ERBB2 gene showed a fair agreement in amplification and polysomy and the level of protein expression in gastric adenocarcinorna. Thus, polysomy 17 could contribute to a high Her-2/neu protein level, at least in gastric cancer. Our data indicated an association with alcohol consumption and the CCND1 gene or protein levels, in both esophageal and gastric cancers. (c) 2006 Elsevier B.V. All rights reserved.

Comparative genomic hybridization analysis of benign and invasive male breast neoplasms

Comparative genomic hybridization (CGH) analysis was performed for the identification of chromosomal imbalances in two benign gynecomastias and one malignant breast carcinoma derived from patients with male breast disease and compared with cytogenetic analysis in two of the three cases. CGH analysis demonstrated overrepresentation of 8q in all three cases. One case of gynecomastia presented gain of 1p34.3similar topter. 11p14similar toq12. and 17p11.2similar toqter, and loss of 1q41similar toqter and 4q33similar toqter. The other gynecomastia presented del(1)(q41) as detected by both cytogenetic and CGH analysis. CGH analysis of the invasive ductal carcinoma confirmed a gain of 17p11.2similar toqter previously detected by cytogenetic analysis. These regions showed some similarity in their pattern of imbalance to the chromosomal alterations described in female and male breast cancer. (C) 2002 Elsevier B.V. All rights reserved.

Monosomy 22 and del(10)(p12) in an ameloblastoma previously diagnosed as an adenoid cystic carcinoma of the salivary gland

Short-term cultures of a collagenase disaggregated ameloblastoma previously diagnosed as an adenoid cystic carcinoma of the salivary gland were shown by cytogenetic analysis to have the clonal karyotype 45,XY,del(10)(p12), -22. The data may indicate that the loss of genes of chromosome 22, as well as of 10p, could be a critical event in the evolutionary pattern of odontogenic neoplasias. (C) Elsevier B.V., 1996

Chromosome breakpoint distribution in nonmelanoma skin cancers

We have identified chromosome regions that may be sites of genes activated as a result of chromosomal rearrangements observed in 61 of the 86 skin tumors referenced in the literature. The data showed that most of the breakpoints were distributed throughout the genome and some tended to cluster. Highest frequencies of breakpoints were observed in chromosomes with high relative length, except chromosomes 14 and 15 that were more often affected in malignant tumors, despite their size. Our work provides a starting point for more detailed studies that may allow identification of these genes as important keys in the development and progression of skin cancers. (C) Elsevier B.V., 1997.

Cytogenetic study of neoplastic and nonneoplastic cells of the skin

We describe the cytogenetic study of six neoplastic and eight nonneoplastic skin samples from sun-exposed body sites or sites close to tumors. The cytogenetic findings revealed that chromosome rearrangements are common in sun-exposed normal skin, similar to the situation in cutaneous tumors, and suggest that such karyotypic abnormalities might be indicative of the genetic instability caused by specific mutations and resulting from carcinogenic exposure of the tissue.

Cytogenetic alterations in chagasic achalasia compared to esophageal carcinoma

Patients with chagasic achalasia (megaesophagus) are liable to have an additional 1.7-20% possibility of developing esophageal squamous cell carcinoma (ESCC). We applied a fluorescence in situ hybridization technique in 20 such patients and found aneuploidies of chromosomes 7, 11, and 17 in 60% (12 of 20 specimens) and deletion of the TP53 gene in 54.5% (6 of 11 specimens; it was only possible to obtain data by FISH technique from 11 of the 20 achalasia patients). The main aneuploidies detected were chromosome 7 monosomy or trisomy (35%) in mid-third megaesophagus cases, and chromosome 17 monosomy or trisomy (25%) in distal-third cases. TP53 gene deletion was more frequent in mid-third (62.5%) than in distal-third megaesophagus cases (40%). In chagasic megaesophagus, no amplification of the cyclin D1 gene (CCND1) was observed. Comparing chagasic megaesophagus to ESCC, we found a higher frequency of aneuploidies in all 10 tumors. The main alterations were trisomy or tetrasomy of chromosomes 17 (90%), 11 (70%), and 7 (70%). Amplification of CCND1 was evidenced as a cluster in 70% of the tumors (22-99% of nuclei), while TP53 gene deletion occurred in 100%. To our knowledge, this is the first cytogenetic analysis of chagasic megaesophagus to show that aneuploidies of chromosomes 7, 11, and 17, and TP53 gene deletion might be related to increased risk for malignancy. (C) 2004 Elsevier B.V. All rights reserved.

Complex cytogenetic rearrangement in a case of unicameral bone cyst

Cytogenetic analysis of a unicameral bone cyst surgically resected in an 11-year-old boy revealed a highly complex clonal structural rearrangement involving chromosomes 4, 6, 8, 16, 21, and both 12. These findings reinforce the need for further studies on unicameral bone cysts to verify the frequency and to understand the significance of chromosome anomalies in this type of lesion.

Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa front 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/ Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors. (C) 2004 Elsevier B.V. All rights reserved.

Multiple cytogenetic clones in a basal cell carcinoma

Chromosome analysis of short-term culture of a basal cell carcinoma showed five clonal chromosome abnormalities, t(9;14)(q12 or q13;p11), del(1)(q23 or q25), trisomy 5, trisomy 7, and monosomy X. In addition, several nonclonal structural and numerical changes were seen in the tumor cells.

Cytogenetic analysis of a multinodular thyroid goiter

Short-term cultures of a collagenase disaggregated multinodular goiter was shown by cytogenetic analysis to have the mosaic karyotype 47,XX,+7/48,XX,+7,+17/49,XX,+7,+10,+17. No cytogenetic data on goiter are available for comparison with the present case.

Translocation (4;14) and concomitant inv(14) in a basal cell carcinoma

Chromosome analysis of short-term cultures from a basal cell carcinoma was performed. The analyzed karyotypes showed a pseudodiploid clone characterized by a der(4)t(4;14)(p14;p11) and a concomitant inversion of the same chromosome 4 involved in the t(4;14) with the breakpoints at p14 and q25.

Cytogenetic findings in two basal cell carcinomas

We describe the cytogenetic study of two basal cell carcinomas. Only single chromosomally abnormal clones could be detected in both. In addition, many nonclonal changes were seen in the samples, which may represent small neoplastic clones or the result of a basic molecular defect induced by carcinogens.

Frequent p53 mutations and occasional loss of chromosome 4 in invasive bladder carcinoma induced by N-butyl-N-(4-hydroxybutil)nitrosamine in B6D2F1 mice

B6D2F1 mice (45/group) were treated with N-butyl-N-(4- hydroxybutyl)nitrosamine (BBN) or uracil as follows: Group 1 received 0.05% BBN in drinking water for the entire experiment, Group 2 received 5 mg of BBN by gastric gavage in 0.1 mL of 20% ethanol twice per week for 10 wk, Group 3 received a 2.5% uracil-containing diet for the entire experiment, and Group 4 was controls (received 0.1 mL of 20% ethanol by gavage twice per week for 10 wk). The surviving mice in Group 1 were killed after week 26 and those in the other groups after week 30. By week 15, three of 11 Group 1 and one of 15 Group 2 mice had bladder carcinoma. By 26 and 30 wk, respectively, invasive carcinomas were observed in 33 of 34 and six of 21 mice in Groups 1 and 2 and renal pelvic carcinomas in 11 of 34 and three of 21 mice in Groups 1 and 2. Four of 19 uracil-treated mice had bladder nodular hyperplasia. By polymerase chain reaction-single-strand conformation polymorphism and sequence analyses, 16 of 20 and two of five bladder carcinomas from Groups 1 and 2, respectively, showed mutations in the p53 gene. Ha-ras mutation was present in one case. Loss of heterozygosity analysis with simple-sequence length polymorphism markers for chromosome 4 showed that 10 of 21, two of 15, and nine of 13 mice in Groups 1-3, respectively, had heterozygous or homozygous deletions. B6D2F1 mice are therefore susceptible to the urothelial carcinogenic effects of BBN and develop frequent p53 mutations and chromosome 4 deletions. Chromosome 4 deletions were also seen with uracil.