Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases

Knösel, Thomas; Petersen, Simone; Schwabe, Holger; Schlüns, Karsten; Stein, Ulf; Schlag, Peter M.; Dietel, Manfred; Petersen, Iver

doi:10.1007/s004280100493

Cited by 79 publications

(78 citation statements)

References 38 publications

(55 reference statements)

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“…HER2 has been reported to be expressed in primary colorectal carcinomas but the levels vary within an extremely wide range, 3-82% (22,23,25,(36)(37)(38)(39)(40)(41)(42). In our study the HER2 expression was nearly zero (one positive case out of 55).…”

Section: ------------------------------------------------------------contrasting

confidence: 39%

EGFR, HER2 and HER3 expression in primary colorectal carcinomas and corresponding metastases: Implications for targeted radionuclide therapy

Wei

Shui²,

Zheng³

et al. 2010

Oncol Rep

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Abstract. Members of the epidermal growth factor receptor, EGFR, family are interesting as targets for radionuclide therapy using targeting agents labeled with ·-or ß-emitting radionuclides, especially when EGFR-positive colorectal carcinomas, CRC, are resistant to EGFR inhibiting agents like cetuximab and various tyrosine kinase inhibitors. The expression of EGFR, HER2 and HER3 was therefore analyzed in CRC samples from primary tumors, corresponding lymph node metastases and, in a few cases, liver metastases. The expression of HER2 and EGFR was scored from immunohistochemical preparations using the HercepTest criteria 0, 1+, 2+ or 3+ for cellular membrane staining while HER3 expression was scored as no, weak or strong cytoplasm staining. Material from 60 patients was analyzed. The number of EGFR 2+ or 3+ positive primary tumors was 16 out of 56 (29%) and for lymph node metastases 8 out of 56 (14%) whereas only one out of nine (11%) liver metastases were positive. Thus, there was lower EGFR positivity in the metastases. Only one among 53 patients was strongly HER2 positive and this in both the primary tumor and the metastasis. Eight out of 49 primary tumors (16%) were strongly HER3 positive and the corresponding numbers for lymph node metastases were 9 out of 49 (18%) and for liver metastases 2 out of 9 (22%). The observed number of strongly EGFR positive cases was somewhat low but EGFR might be, for the cases with high EGFR expression in metastases, a target for radionuclide therapy. HER2 seems not to be of such interest due to rare expression, neither HER3 due to mainly expression in the cytoplasm. The requirements for successful EGFR targeted radionuclide therapy are discussed, as well as patient inclusion criteria related to radionuclide therapy.

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Section: ------------------------------------------------------------contrasting

confidence: 39%

EGFR, HER2 and HER3 expression in primary colorectal carcinomas and corresponding metastases: Implications for targeted radionuclide therapy

Wei

Shui²,

Zheng³

et al. 2010

Oncol Rep

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“…In the colorectal cancer cell line, we detected possible selective losses of chromosomes 11 and 20. Previous studies on colorectal cancers (45)(46)(47)(48)(49) showed complex cytogenetic profiles in which the gain of chromosomes 20, 7, and 13, and the loss of chromosomes 4 and 18, were commonly observed. Interestingly, the selective losses of chromosomes 11 and 20 have also been previously detected.…”

Section: Discussionmentioning

confidence: 99%

Exposure to the Tobacco Smoke Constituent 4-Aminobiphenyl Induces Chromosomal Instability in Human Cancer Cells

et al. 2007

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The relationships between environmental factors and the genetic abnormalities that drive carcinogenesis are supported by experimental and epidemiologic evidence but their molecular basis has not been fully elucidated. At the genomic level, most human cancers display either chromosomal (CIN) or microsatellite (MIN) instability. The molecular mechanisms through which normal cells acquire these forms of instability are largely unknown. The arylamine 4-aminobiphenyl (4-ABP) is a tobacco smoke constituent, an environmental contaminant, and a well-established carcinogen in humans. Among others, bladder, lung, colon, and breast cancers have been associated with 4-ABP. We have investigated the effects of 4-ABP and N-methyl-N '-nitro-N-nitrosoguanidine (MNNG) on genetically stable colorectal (HCT116) and bladder (RT112) cancer cells. Cells were treated with carcinogens to generate resistant clones that were then subjected to genetic analysis to assess whether they displayed either CIN or MIN. We found that 50% to 60% of cells treated with 4-ABP developed CIN but none developed MIN as confirmed by their ability to gain and lose chromosomes. In contrast, all MNNG-treated clones (12/12) developed MIN but none developed CIN as shown by the microsatellite assay. The mismatch repair protein expression analysis suggests that the acquired mechanism of MIN resistance in the HCT116 MNNG-treated cells is associated with the reduction or the complete loss of MLH1 expression. By providing a mechanistic link between exposure to a tobacco constituent and the development of CIN, our results contribute to a better understanding of the origins of genetic instability, one of the remaining unsolved problems in cancer research. [Cancer Res 2007;67(15):7088-94]

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“…Recent studies indicate that Rho proteins regulate signaling pathways that mediate tumor cell invasion and metastasis (Sliva et al, 2000;Tsutsumi et al, 2002). DLC-1 gene was mapped to the 8p21.3-22, a region that is frequently deleted during the process of metastasis of lung cancer (Kurimoto et al, 2001), colorectal cancer (Knosel et al, 2002), and melanoma (Wiltshire et al, 2001). Moreover, a recent study using Gene-chip array technology analysed the different transcriptional profiles of two human mammary carcinoma cell lines, which showed metastatic and nonmetastatic properties, and reported that DLC-1 was downregulated in the metastatic cell line (Euer et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells

et al. 2003

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Southern analysis showed that seven of nine human gastric cancer cell lines did not express DLC-1 mRNA, but contained the DLC-1 gene. To identify the mechanism of the loss of DLC-1 mRNA expression in these cell lines, we investigated the methylation status of DLC-1 gene by using methylation-specific PCR (MSP) and Southern blot, and found that five of seven DLC-1 nonexpressing gastric cancer cell lines were methylated in the DLC-1 CpG island. Treatment with 5-aza-2 0 -deoxycytidine (5-Aza-dC) induced DLC-1 mRNA expression in the gastric cancer cell lines that have the methylated alleles. Studies using SNU-601 cell line with methylated DLC-1 alleles revealed that nearly all CpG sites within DLC-1 CpG island were methylated, and that the in vitro methylation of the DLC-1 promoter region is enough to repress DLC-1 mRNA expression, regardless of the presence of transcription factors capable of inducing this gene. In all, 29 of 97 (30%) primary gastric cancers were also shown to be methylated, demonstrating that methylation of the DLC-1 CpG island is not uncommon in gastric cancer. In addition, we demonstrated that DLC-1 mRNA expression was induced, and an increase in the level of acetylated H3 and H4 was detected by the treatment with trichostatin A (TSA) in two DLC-1 nonexpressing cell lines that have the unmethylated alleles. Taken together, the results of our study suggest that the transcriptional silencing of DLC-1, by epigenetic mechanism, may be involved in gastric carcinogenesis.

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Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases

Cited by 79 publications

References 38 publications

EGFR, HER2 and HER3 expression in primary colorectal carcinomas and corresponding metastases: Implications for targeted radionuclide therapy

EGFR, HER2 and HER3 expression in primary colorectal carcinomas and corresponding metastases: Implications for targeted radionuclide therapy

Exposure to the Tobacco Smoke Constituent 4-Aminobiphenyl Induces Chromosomal Instability in Human Cancer Cells

Transcriptional silencing of the DLC-1 tumor suppressor gene by epigenetic mechanism in gastric cancer cells

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