17 research outputs found
Interphase cytogenetics of prostatic adenocarcinoma
In the first part of this chapter an overview will be presented on the structural,
histological and functional aspects of the normal human prostate. The second part
describes the epidemiological and clinicopathological features of prostatic
adenocarcinoma. Further, a state of the art of (cyto)genetic aberrations occurring in
prostatic cancer is given. The third part of this introduction will discuss
methodological aspects of this thesis, i.e., the development and methodology of
non-isotopic in situ hybridization. Finally, the scope of this thesis will be presented
Interphase cytogenetics and comparative genomic hybridization of human epithelial cancers and precursor lesions
Effect of bone decalcification procedures on DNA in situ hybridization and comparative genomic hybridization. EDTA is highly preferable to a routinely used acid decalcifier
Decalcification is routinely performed for histological studies of
bone-containing tissue. Although DNA in situ hybridization (ISH) and
comparative genomic hybridization (CGH) have been successfully employed on
archival material, little has been reported on the use of these techniques
on archival decalcified bony material. In this study we compared the
effects of two commonly used decalcifiers, i.e. , one proprietary,
acid-based agent (RDO) and one chelating agent (EDTA), in relation to
subsequent DNA ISH and CGH to bony tissues (two normal vertebrae, six
prostate tumor bone metastases with one sample decalcified by both EDTA
and RDO). We found that RDO-decalcified tissue was not suited for DNA ISH
in tissue sections with centromere-specific probes, whereas we were able
to adequately determine the chromosomal status of EDTA-decalcified
material of both control and tumor material. Gel electrophoresis revealed
that no DNA could be successfully retrieved from RDO-treated material.
Moreover, in contrast to RDO-decalcified tumor material, we detected
several chromosomal imbalances in the EDTA-decalcified tumor tissue by CGH
analysis. Furthermore, it was possible to determine the DNA ploidy status
of EDTA- but not of RDO-decalcified material by DNA flow cytometry.
Decalcification of bony samples by EDTA is highly recommended for
application in DNA ISH and CGH techniques
Molecular cytogenetic evaluation of gastric cardia adenocarcinoma and precursor lesions
Analyses of cancer incidence data in the United States and Western Europe
revealed steadily rising rates over the past decades of adenocarcinomas of
the esophagus and gastric cardia. Genetic information on gastric cardia
adenocarcinoma and its preneoplasias is sparse. We have used comparative
genomic hybridization to obtain a genome-wide overview of 20 archival
gastric cardia adenocarcinomas and 10 adjacent preneoplastic lesions (
Genomic alterations in malignant transformation of Barrett's esophagus
The incidence of adenocarcinoma in Barrett's esophagus has been increasing
rapidly over the past decades. Neoplastic progression is characterized by
three well-defined premalignant stages: metaplasia, low-grade dysplasia,
and high-grade dysplasia. A genome-wide overview, based on comparative
genomic hybridization, was performed, evaluating 30 Barrett's
adenocarcinomas and 25 adjacent precursors, i.e., 6 metaplasias, 9
low-grade dysplasias, and 10 high-grade dysplasias. The frequency of
losses and gains significantly increased in the subsequent stages of
malignant transformation. Losses of 5q21-q23, 9p21, 17p12-13.1, 18q21, and
Y were revealed in low-grade dysplasias. This was followed by loss of
7q33-q35 and gains of 7p12-p15, 7q21-q22, and 17q21 in high-grade
dysplasias along with high-level amplification (HLA) of 7q21 and 17q21. In
the invasive cancers, additional losses of 3p14-p21, 4p, 4q, 8p21,
13q14-q31, 14q24.3-q31, 16q21-q22, and 22q as well as gains of 3q25-q27,
8q23-24.1, 12p11.2-12, 15q22-q24, and 20q11.2-q13.1 were distinguished
along with HLAs of 8p12-p22 and 20q11.2-q13.1. Approximately one-third of
the alterations in the dysplasias were also found in the adjacent
adenocarcinomas, illustrating that multiple clonal lineages can be present
in Barrett's esophagus. Novel findings include loss on 7q, gain on 12p,
and the observation of several HLAs in high-grade dysplasias. Furthermore,
loss of 7q33-q35 was found to represent a significant distinction between
low-grade and high-grade dysplasia (P = 0.01), whereas loss of 16q21-q22
and gain of 20q11.2-q13.1 were disclosed to significantly discriminate
between high-grade dysplasia and adenocarcinoma (P = 0.02 and P = 0.03,
respectively). This inventory of genetic aberrations increases our
understanding of malignant transformation in Barrett's esophagus and might
provide useful biomarkers for disease progression
Interphase in situ hybridization to disaggregated and intact tissue specimens of prostatic adenocarcinomas
Molecular cytogenetic analysis of prostatic adenocarcinomas from screening studies : early cancers may contain aggressive genetic features
No objective parameters have been found so far that can predict the
biological behavior of early stages of prostatic cancer, which are
encountered frequently nowadays due to surveillance and screening
programs. We have applied comparative genomic hybridization to routinely
processed, paraffin-embedded radical prostatectomy specimens derived from
patients who participated in the European Randomized Study of Screening
for Prostate Cancer. We defined a panel consisting of 36 early cancer
specimens: 13 small (total tumor volume (Tv) < 0.5 ml) carcinomas and 23
intermediate (Tv between 0.5-1.0 ml) tumors. These samples were compared
with a set of 16 locally advanced, large (Tv > 2.0 ml) tumor samples, not
derived from the European Randomized Study of Screening for Prostate
Cancer. Chromosome arms that frequently (ie, > or = 15%) showed loss in
the small tumors included 13q (31%), 6q (23%), and Y (15%), whereas
frequent (ie, > or = 15%) gain was seen of 20q (15%). In the intermediate
cancers, loss was detected of 8p (35%), 16q (30%), 5q (26%), Y (22%), 6q,
and 18q (both 17%). No consistent gains were found i