Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.

Background: Colorectal cancer (CRC) represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D) CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs.

Single nucleotide polymorphism array analysis of microsatellite-stable, diploid/near-diploid colorectal carcinomas without the CpG island methylator phenotype.

Colorectal carcinomas are considered to progress by chromosomal instability (CIN), or microsatellite instability (MSI) and/or epigenetic gene silencing; however, in previous studies we observed a small fraction of tumours without this molecular phenotype. To further investigate these 'X-type' tumours, neoplastic glands from five tumours were isolated by laser-capture microdissection and used for single nucleotide polymorphism (SNP) array analyses. DNA from our own low-passage primary colorectal carcinoma cell lines (n=9) was used for comparison.

Ex-vivo clonally expanded B lymphocytes infiltrating colorectal carcinoma are of mature immunophenotype and produce functional IgG.

Background: Tumor infiltrating B cells (TiBc) have not yet been investigated in detail. This may at least in part be due to technical difficulties. Here we describe a straightforward and reproducible method to isolate and culture TiBc from primary colorectal carcinomas (CRC).

Cryopreservation of human colorectal carcinomas prior to xenografting.

Background: Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this.

Chromosomally and microsatellite stable colorectal carcinomas without the CpG island methylator phenotype in a molecular classification.

We hypothesized that in a comprehensive analysis of colorectal carcinomas (CRC) the three currently known major molecular mechanisms of carcinogenesis (i.e., chromosomal instability, microsatellite instability, and CpG island methylator phenotype, CIMP) would associate with the molecular features indicative of these pathways, allowing a molecular classification.

High-degree tumor budding and podia-formation in sporadic colorectal carcinomas with K-ras gene mutations.

In vitro ras activation enhances the epithelial-mesenchymal transition of colorectal carcinoma cells. But ras effects are known to be highly dependent on cell types and the tissue context. Therefore, this study was made to test the hypothesis that in clinical colorectal carcinoma specimens, aggressive invasion phenotypes, specifically tumor budding and podia formation, would correlate with K-ras gene mutations.

Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy in stage III colonic adenocarcinoma?

Since 5-fluorouracil (5-FU)-based chemotherapy has become standard adjuvant treatment for patients with node-positive colonic adenocarcinoma, there has arisen the need for predictive factors. Thymidylate synthase (TS) is a major target of 5-FU's action, and high TS expression in carcinoma cells could reduce its cytostatic effect. Both, a 28-base pair repeat polymorphism and a cytosine vs.

p16(INK4a) promoter methylation and 9p21 allelic loss in colorectal carcinomas: relation with immunohistochemical p16(INK4a) expression and with tumor budding.

In colorectal carcinomas, p16(INK4a) inactivation is known to occur by allelic loss and by promoter methylation, but mutations are rare. p16(INK4a) is up-regulated in tumor buds, and the consequent shutdown of proliferation may be a prerequisite for tumor budding. Fifty-seven colorectal carcinomas from a consecutive series were investigated.

Expression profiling of colorectal carcinomas using tissue microarrays: cell cycle regulatory proteins p21, p27, and p53 as immunohistochemical prognostic markers in univariate and multivariate analysis.

With the rapidly growing understanding of tumor biology, molecular staging of cancer is expected to improve prognostication. This would be particularly important for cancers amenable to adjuvant treatment, such as colorectal carcinomas. To generate data for this, the tissue microarray technique may prove useful.

Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability.

Previous studies have identified high numbers of intraepithelial T lymphocytes to be associated with good prognosis in various types of cancer. Few studies addressing this issue have been published for colorectal cancer. In a simulated prospective approach ("phase II prognostic factor study"), all nonmetachronous International Union Against Cancer (UICC) stage III colorectal cancers that were accessioned in the years 1994 to 1999 were included in the study (152 cases).

Human papillomavirus 6/11, 16 and 18 in oral carcinomas and benign oral lesions.

We have examined 118 oral squamous cell carcinomas, 72 oral leukoplakias, 12 cases of cheilitis and 65 of oral lichen planus for the presence of human papillomavirus (HPV) 6/11, 16 and 18 DNA by PCR/Southern blot hybridization. HPV DNA were found in 51/118 carcinomas (43.2%), in 16/72 (22.