Biomedical subjects

Jan Baak

Publications and source records attributed to Jan Baak.

4 recordsLinked to original sources

PubMed2005

Nuclear size distinguishes low- from high-grade ovarian serous carcinoma and predicts outcome.

A dualistic model for ovarian serous carcinogenesis based on morphological and molecular genetic studies has recently been proposed. This model divides serous carcinoma into low- and high-grade tumors, which develop along distinct molecular pathways. In this report, we evaluated computerized morphometry to determine its utility in distinguishing low- and high-grade serous carcinoma. The mean nuclear area (MNA) and the volume percentage of epithelium (VPE) in 93 high-grade serous carcinomas was measured and compared with 16 low-grade serous carcinomas and 21 serous borderline tumors, the putative precursor of low-grade serous carcinoma. We found that both MNA and VPE were significantly higher in high-grade serous carcinoma compared with low-grade serous carcinoma and serous borderline tumors (P < .001 and P = .02, respectively). There was no significant difference in MNA and VPE between low-grade carcinoma and serous borderline tumors (P > .3). Among high-grade serous carcinomas, those with an MNA of 46 microm2 or higher had a poorer survival (P = .035) than those with an MNA below 46 microm2. In contrast, VPE and tumor grade (moderately versus poorly differentiated) had no significant prognostic value. The morphometry findings lend further support to the dualistic model of ovarian serous carcinogenesis and suggest that MNA is an excellent adjunctive tool for distinguishing low- from high-grade serous carcinomas. In addition, MNA is an independent prognostic factor for high-grade serous carcinoma.

Cell Nucleus↗

PubMed2005

Centromeric chromosomal translocations show tissue-specific differences between squamous cell carcinomas and adenocarcinomas.

Structural chromosomal aberrations are common in epithelial tumors. Here, we compared the location of centromeric breaks associated with whole arm translocations in seven adenocarcinoma cell lines and nine squamous cell carcinoma cell lines using SKY, microarray-based comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH). Whole arm translocations were more frequent in squamous cell carcinomas (112 in nine cell lines and nine in one short-term culture) than in adenocarcinomas (13 in seven cases) and most often resulted in copy number alterations. Array CGH analysis demonstrated that in all squamous cell carcinomas and in most adenocarcinomas, the breakpoints of unbalanced whole arm translocations occurred between the two clones on the array flanking the centromeres. However, FISH with centromeric probes revealed that in squamous cell carcinomas, the marker chromosomes with whole arm translocations contained centromeres comprised of material from both participating chromosomes, while in adenocarcinomas centromeric material from only one of the chromosomes was present. These observations suggest that different mechanisms of centromeric instability underlie the formation of chromosomal aberrations in adenocarcinomas and squamous cell carcinomas.

Adenocarcinoma↗

PubMed2003

LOH of PTPRJ occurs early in colorectal cancer and is associated with chromosomal loss of 18q12-21.

Recently, the gene PTPRJ (protein tyrosine phosphatase receptor type J) was identified as the candidate gene for the mouse colon cancer susceptibility locus Scc1. Its human homologue PTPRJ is frequently deleted in several cancer types, including colorectal cancer. To elucidate the role of PTPRJ loss in different stages of colorectal cancer and in its pathways of progression, we expanded the previously published comparative genomic hybridization results with novel data on loss of heterozygosity (LOH) at the PTPRJ locus. We identified a strong association between the LOH of PTPRJ and the loss of chromosomal region 18q12-21 (P=0.009). This observation is specific for progressed colorectal adenomas, suggesting that an interaction between LOH of PTPRJ and loss of 18q12-21 may be involved in the development of a more progressed form of adenomas.

Adenoma↗

PubMed2002

Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability.

BACKGROUND & AIMS: Current models of colorectal adenoma to carcinoma progression do not fully reflect the genetic heterogeneity and complexity of the disease. The aim of the present study was to identify genetic changes discriminating adenomas that have progressed to carcinoma from adenomas that have not progressed, and to refine the current genetic models of colorectal adenoma to carcinoma progression, based on a genome-wide analysis of chromosomal aberrations. METHODS: Sixty-six nonprogressed colorectal adenomas, 46 progressed adenomas (malignant polyps), and 36 colorectal carcinomas were screened for chromosomal aberrations by comparative genomic hybridization, and for mutations in the adenomatous polyposis coli (APC) and K-ras gene. Data analysis focused on cancer-associated genetic changes in adenomas. RESULTS: Accumulation of losses in 8p21-pter, 15q11-q21, 17p12-13, and 18q12-21, and gains in 8q23-qter, 13q14-31, and 20q13 were strongly associated with adenoma-to-carcinoma progression, independent of the degree of dysplasia. Hierarchic cluster analysis demonstrated the presence of 3 distinct subgroups of adenomas, characterized by unique combinations of genetic aberrations in the adenomas (17p loss and K-ras mutation, 8q and 13q gain, and 18q loss and 20q gain, respectively). CONCLUSIONS: The presence of 2 or more of the aforementioned 7 chromosomal changes was associated with progressed colorectal adenomas and colorectal cancer. In addition, evidence was found that these chromosomal abnormalities occurred in specific combinations of a few abnormalities rather than as a mere accumulation of events, indicating the existence of multiple independent chromosomal instability pathways of colorectal cancer progression.

Adenoma↗