PURPOSE: E2F-1 is a transcriptor that converts G1 to S in the cell cycle, and Topoisomerase II-alpha is a key enzyme in the metabolism of DNA, and an indicator of cell replication. The purpose of this study was to evaluate the clinical validity of E2F-1 and Topoisomerase II-alpha as prognostic factors in colorectal cancer. METHODS: The expressions of E2F-1 and Topoisomerase II-alpha were studied immunohistochemically using tumor specimen sections fixed with formalin and paraffin-embedded for 84 cases of colorectal cancer. The correlation between E2F-1 and Topoisomerase II-alpha expressions, and their relationship with the clinicopathological factors, such as tumor differentiation, tumor invasion, lymph node metastasis and tumor stage were investigated. RESULTS: Of the 84 specimens, 43 (51.2%) were immunohistochemically negative for E2F-1, and 41 (48.8%) were positive. The expression of E2F-1 correlated with poor tumor differentiation, increased lymph node metastasis and high tumor stage. The expression of Topoisomerase II-alpha also correlated with poor tumor differentiation, increased lymph node metastasis and high tumor stage. The E2F-1 and Topoisomerase II-alpha expressions indices were significantly correlated. CONCLUSION: These results suggest that the expressions of E2F-1 and DNA Topoisomerase II-alpha may play a role as a prognostic factor for colorectal cancer, but further studies will be required for its comfirmation.
Cell Cycle ; Colorectal Neoplasms* ; DNA ; DNA Topoisomerases, Type I* ; Formaldehyde ; Lymph Nodes ; Metabolism ; Neoplasm Metastasis

Carcinoma, Hepatocellular ; genetics ; metabolism ; DNA Methylation ; DNA Restriction Enzymes ; metabolism ; DNA, Neoplasm ; genetics ; Glutathione S-Transferase pi ; genetics ; metabolism ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Polymerase Chain Reaction ; methods

OBJECTIVETo detect the correlation between the expression of topoisomerase 2 alpha (TOP2A) and the biological behaviors of human colorectal carcinoma.

METHODSImmunohistochemistry and real-time RT-PCR were used to detect the expression of TOP2A in colorectal carcinomas and normal mucosa.

RESULTSThe protein and mRNA expressions of TOP2A in the metastatic lymph nodes were significantly higher than those in matched primary lesions and normal tissues (P<0.05). No significant difference was found in TOP2A expressions between normal mucosa and colorectal carcinomas. The protein and mRNA expressions of TOP2A were significantly correlated to the lymph node metastasis and invasion depth (P<0.05), but not to the differentiation of the tumor (P>0.05).

CONCLUSIONTOP2A plays an important role in the invasion and metastasis of the colorectal carcinomas, and may serve as a valuable indicator for the diagnosis, treatment and the prognostic evaluation of the malignancy.

Antigens, Neoplasm ; metabolism ; Colorectal Neoplasms ; metabolism ; pathology ; DNA Topoisomerases, Type II ; metabolism ; DNA-Binding Proteins ; metabolism ; Female ; Humans ; Lymphatic Metastasis ; Male ; Poly-ADP-Ribose Binding Proteins

Antigens, Neoplasm ; genetics ; metabolism ; Breast Neoplasms ; enzymology ; genetics ; metabolism ; DNA Topoisomerases, Type II ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; physiology ; Humans

To determine whether family history of cancer may be a risk factor for the mutator phenotype in colorectal cancer, we recruited 143 consecutive colorectal cancer patients with a family history of accompanying cancers not meeting the Amsterdam criteria. Microsatellite instability (MSI) at 5 markers, hMLH1-promoter methylation, and expression of mismatch repair (MMR) proteins (hMLH1, hMSH2, hMSH6, hMPS1, and hPMS2) were determined. Among the relatives of familial colorectal cancer patients, colorectal cancer was the most common tumor type. Of the proband colorectal cancers, 26 (18.2%) showed high-level MSI (MSI-H); 47 additional tumors with mutator phenotype (32.9%) were identified by hMLH1-promoter methylation and/or loss of MMR protein expression. Mutator phenotype was associated with right-sided colon cancer and the type of accompanying cancer. Family history, which was differentially quantified according to the degree of relatives and the type of accompanying cancers, effectively discriminated MSI-H from microsatellite stable (MSS) and low-level microsatellite instability (MSI-L) and mutator phenotypes. Our findings indicate that familial colorectal cancer may be associated with multiple occurrences of colorectal or accompanying cancers and that family history could be correlated with microsatellite instability.
Adaptor Proteins, Signal Transducing/genetics/metabolism ; Adenosine Triphosphatases/metabolism ; Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Colorectal Neoplasms/*genetics/metabolism/pathology ; DNA Methylation ; DNA Mismatch Repair ; DNA Repair Enzymes/metabolism ; DNA, Neoplasm/genetics ; DNA-Binding Proteins/metabolism ; Female ; Humans ; Male ; *Microsatellite Instability ; Middle Aged ; MutS Homolog 2 Protein/metabolism ; Neoplasm Proteins/metabolism ; Nuclear Proteins/genetics/metabolism ; Phenotype ; Promoter Regions, Genetic ; Risk Factors

OBJECTIVETo analyze the relationship between DNA content and biological behavior and its prognostic significance in non-small cell lung cancer.

METHODSTumor DNA content was determined by flow cytometry in the specimens from 58 patients with resected non-small cell lung cancer. The DNA content of each cell subpopulation was expressed as the DNA index (DI), and an internal standard was provided by the normal pulmonary parenchymal cells in the same specimen. The prognostic value of DNA content in non-small cell lung cancer was assessed by Cox's model analysis.

RESULTSIn qualitative analysis, there was no relationship between DNA ploidy (diploidy or aneuploidy) and the following factors: tumor size, metastasis of lymph node, clinical stage, pathologic type, pathologic grade or survival. In quantitative analysis, high DNA index was observed in tumor size > 3 cm, metastasis of lymph node, stage III/IV, adenocarcinoma and shorter survival, which was statistically significant. Cox's model analysis showed that DNA index was a prognostic factor in non-small cell lung cancer and DNA index > 2.0 was an independent prognostic factor.

CONCLUSIONDNA index analysis is useful for the evaluation of the biological behavior and the prognosis of non-small cell lung cancer.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; DNA, Neoplasm ; metabolism ; Female ; Humans ; Lung Neoplasms ; metabolism ; Male ; Middle Aged

The proliferative activity of human gastric carcinoma was measured by means of in vitro incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), into the newly-synthesized DNA of fresh tumors and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) using avidin-biotin peroxidase method. Eighty-two cases of surgically resected human gastric carcinomas consisting of 18 various histologic types were subjected to study. The mean BrdU labelling index (LI) and PCNA LI were 22.9% and 39.1%, respectively. The correlation between BrdU LI and PCNA LI was statistically significant (correlation coefficient mu = 0.61334, p = 0.0001). We concluded that immunohistochemical staining for PCNA may become a practical method instead of in vitro or in vivo BrdU labeling to assess the proliferation fraction of the gastric cancer patient.
Antibodies, Monoclonal ; Antigens, Neoplasm/*metabolism ; Bromodeoxyuridine/*metabolism ; Carcinoma/*metabolism/pathology ; Cell Division ; DNA Replication ; DNA, Neoplasm/biosynthesis ; Humans ; Immunoenzyme Techniques ; Nuclear Proteins/*metabolism ; Proliferating Cell Nuclear Antigen ; Stomach Neoplasms/*metabolism/pathology ; Tumor Cells, Cultured

OBJECTIVETo investigate the expression of GST-pi and Topo II-alpha, and their relationships with clinicopathological parameters in colorectal carcinoma.

METHODSThe expression of GST-pi and Topo II-alpha were detected by avidin-biotin-peroxide complex (ABC) method in tumor specimens, matched paratumor tissues from 60 cases with colorectal carcinoma and normal colonic tissues from 15 cases.

RESULTSThe expression rates of GST-pi and Topo II-alpha were 90.0% and 86.7% respectively in tumor tissues, significantly higher than those in matched paratumor tissues and normal tissues (P< 0.01). The expressions of GST-pi and Topo II-alpha were associated with cellular differentiation, Dukes stage and lymph node metastasis (all P< 0.01), but not with tumor size and histological type (all P > 0.05). The expression level of GST-pi was significantly higher in poorly differentiated tumors than that in well differentiated tumors. The expression level of Topo II-alpha in well-differentiated tumors were stronger than that in poorly differentiated tumors.

CONCLUSIONSThe detection of GST-pi and Topo II-alpha expressions may be helpful to judge the malignant behavior, metastasis and prognosis in human colorectal carcinoma.

Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; metabolism ; Colorectal Neoplasms ; metabolism ; pathology ; DNA Topoisomerases, Type II ; metabolism ; DNA-Binding Proteins ; metabolism ; Female ; Glutathione S-Transferase pi ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging

OBJECTIVETo make quantitative analysis of DNA content of breast cancer with neuroendocrine (NE) cells and its significance.

METHODSUsing MIPS-III image analyzer, DNA content and 9 parameter measurements of the tumor nuclei were made in both NE positive (17) and negative (64) breast carcinomas.

RESULTSOut of 81 breast carcinomas, 17 cases were NE positive while 64 cases were NE negative. In the NE (+) cases, the integral optic density, mean optic density, DNA index, DNA stemlines peak, > 5c aneuploidy cells and the rate of aneuploidy cells were all lower than those in the NE negative breast carcinoma cases (P < 0.01). The positive rates of NE cells were 32.5% and 7.9% in grade I - II breast carcinomas and in grade III breast carcinomas respectively with significant difference between the two groups (P < 0.01).

CONCLUSIONOur study shows that NE (+) breast carcinomas have lower DNA parameters than NE (-) breast carcinomas, suggesting that NE (+) breast carcinomas have lower malignancy.

Aneuploidy ; Breast Neoplasms ; genetics ; pathology ; Carcinoma, Neuroendocrine ; genetics ; pathology ; DNA, Neoplasm ; genetics ; metabolism

Animals ; Annexin A2 ; chemistry ; genetics ; metabolism ; physiology ; DNA Replication ; Endocytosis ; Exocytosis ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms ; metabolism ; pathology ; Prognosis ; Tissue Plasminogen Activator ; metabolism ; physiology