PubMed Health⌕ Search

Biomedical subjects

Holger Moch

Publications and source records attributed to Holger Moch.

40 records · Page 3Linked to original sources
PubMed2002

Chromosomal alterations in hepatocellular nodules by comparative genomic hybridization: high-grade dysplastic nodules represent early stages of hepatocellular carcinoma.

Data from experimental hepatocarcinogenesis and recent studies in humans have suggested that the emergence of hepatocellular carcinoma (HCC) is a stepwise process. However, despite abundant experimental data, the precise molecular mechanisms and genetic alterations involved in human liver carcinogenesis are still unclear. Comparative genomic hybridization was used to analyze 26 hepatocellular nodules obtained from patients undergoing liver transplantation or surgical resection for HCC. According to the criteria proposed by the International Working Party, 16 nodules were classified as multiacinar regenerative nodules (MRN), 4 as low-grade dysplastic nodules (LG-DN), and 6 as high-grade dysplastic nodules (HG-DN). Our aim was to investigate the possible genetic differences between MRN, LG-DN, and HG-DN. The whole group of nodules showed only a few aberrations (mean 1.1/case), without any significant pattern. This finding is comparable to what happens in non-neoplastic tissue. On the contrary, in three of six HG-DN, we found deletions of 8p and gains of 1q. LG-DN and MRN did not show these chromosomal imbalances. These results confirm the important role of allelic losses on 8p as well as of gains of 1q in HCC. We conclude that the genes that are important in early stages of hepatocarcinogenesis are probably located on these chromosomal arms.

Carcinoma, Hepatocellular↗
PubMed2002

DNA sequence losses on chromosomes 11p and 18q are associated with clinical outcome in lymph node-negative ductal breast cancer.

PURPOSE: Histological and other markers alone cannot predict the risk of disease progression in node-negative breast cancer. Several genomic aberrations have been linked to clinical outcome in breast cancer. EXPERIMENTAL DESIGN: In this study, comparative genomic hybridization was applied to screen for specific DNA copy number gains and losses in 20 pT1/pT2 node-negative invasive ductal carcinomas with no disease recurrence with at least 8 years of follow-up and in 20 pT1/pT2 node-negative tumors with distant disease recurrence. RESULTS: The number of genomic aberrations (copy number gains and losses) per tumor was significantly higher in tumors with disease recurrence (P < 0.05). The number of genomic aberrations was associated with histological grade (P < 0.02). Within the group of tumors with disease recurrence, the total number of genetic aberrations per tumor (P < 0.02) and the number of DNA sequence losses per tumor (P < 0.01) were significantly associated with poor survival. Of the individual loci involved, only losses at chromosomes 11p (P < 0.002) and 18q (P < 0.004) were associated with poor survival in the recurrence group. Histological grade and loss of 18q were independent prognostic variables in multivariate analysis. CONCLUSIONS: This genome-wide analysis by comparative genomic hybridization suggests that node-negative ductal breast cancers with a high number of genomic aberrations have an increased risk of disease recurrence. The number of DNA sequence losses, particularly losses of chromosomes 11p and 18q, were associated with poor prognosis. Genes on chromosomes 11p and 18q may play a role in the progression of ductal breast carcinoma.

Breast Neoplasms↗
PubMedDate not supplied

Molecular and clinicopathological analysis of ovarian carcinomas with and without microsatellite instability.

BACKGROUND: Microsatellite instability (MSI) occurs in sporadic ovarian carcinomas. This study tests the hypothesis that ovarian carcinomas arising through the mutator pathway have distinctive clinical and molecular features that affect clinical outcome. MATERIALS AND METHODS: The MSI status was evaluated in 66 ovarian carcinomas and 11 epithelial ovarian tumors of low malignant potential. For the analysis with the microsatellite markers, a fluorescence-based PCR method was employed and the prognostic significance of the MSI status was assessed. DNA copy number changes in tumors with and without MSI were analyzed by comparative genomic hybridization. RESULTS: High-frequency MSI (MSI-H) was found in 30% of the carcinomas, whereas low-frequency MSI (MSI-L) occurred in 32%. In LMP tumors, only MSI-L was detected (18%). There was a trend for tumors with MSI-H and MSI-L to have a poor prognosis, but this relationship did not reach significance (p=0.09 and p=0.07, respectively). MSI-H in carcinomas was significantly associated with poor differentiation (p=0.03) and higher clinical stage (p=0.03). No correlation was found between different histological types of ovarian carcinoma and the microsatellite status. In a multivariate analysis, MSI at the dinucleotide repeat D5S346 was found to be of independent prognostic significance (p<0.008) for disease-specific survival. There was no association between the total number of genetic aberrations per tumor and the MSI status. CONCLUSION: Microsatellite instability is a relatively common event in ovarian carcinoma. The data indicate that instability of a single microsatellite marker on chromosome 5 (D5S346) might be indicative of disease progression when detected in early clinical stages.

Adaptor Proteins, Signal Transducing↗