Adenocarcinoma, Mucinous ; enzymology ; pathology ; Cathepsin B ; metabolism ; Cathepsin D ; metabolism ; Colorectal Neoplasms ; enzymology ; pathology ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness

OBJECTIVETo explore the expression of manganese superoxide dismutase (MnSOD) in colorectal carcinoma and its relationship with the clinicopathological findings.

METHODSThe expressions of MnSOD in colorectal carcinoma, adenoma, and adjacent corresponding intestinal mucosal tissues were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The relationship between MnSOD expression level in colorectal adenoma and clinical parameters was analyzed.

RESULTSThe expression of MnSOD was negative in adjacent corresponding colorectal tissues. The positive expression rate of MnSOD was 44% (11/25) in colorectal adenoma and 76% (19/25) in colorectal carcinoma (P < 0.05 when compared with the colorectal adenoma and its adjacent tissues). The expression of MnSOD was positively correlated with histopathological grades (P < 0.05) but not with other clinicopathological findings (P > 0.05).

CONCLUSIONThe expression of MnSOD may be associated with the carcinogenesis and progression of colorectal carcinoma, and therefore may be used as a new biomarker.

Adult ; Aged ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Male ; Middle Aged ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the expression of PI3K p85alpha in normal colorectal tissue, colorectal adenoma and primary colorectal carcinoma and explore its significance in the progression of colorectal cancer.

METHODSThe expression of PI3K p85alpha was detected in 116 normal colorectal tissue, colorectal adenoma and primary colorectal carcinoma specimens using immunohistochemical staining, and the relationship between the expression of PI3K p85alpha protein and the clinicopathological factors was analyzed.

RESULTSThe positivity rates of the expression of PI3K p85alpha protein increased gradually in the progression of colorectal cancer and showed significant differences between the tissues (P<0.05). A significant difference was also noted in the positivity rates of the PI3K p85alpha expression in colorectal carcinoma tissues at different Dukes' stages (P<0.05). No obvious correlation was found between PI3K p85alpha expression and the degree of the tumor differentiation.

CONCLUSIONSAbnormal PI3K p85alpha expression occurs in the progression of colorectal cancer in close relation to the clinical stage, and the PI3K/AKT pathway plays an important role in the progression of colorectal cancer.

Adenoma ; enzymology ; pathology ; Adult ; Aged ; Carcinoma ; enzymology ; pathology ; Colorectal Neoplasms ; enzymology ; pathology ; Disease Progression ; Humans ; Immunohistochemistry ; Middle Aged ; Phosphatidylinositol 3-Kinases ; metabolism ; Signal Transduction ; Young Adult

OBJECTIVETo study the thymidine phosphorylase (TP) expression in different types of cancer and its correlation with tumor microvessel density (MVD).

METHODSThe expression of TP and MVD was detected by immunohistochemistry method. In a series of 251 cancer patients there were 48 patients with gastric cancer, 53 with colorectal cancer, 47 with breast cancer, 56 with cervical cancer, 47 with lung cancer. Normal gastric (n = 25), colorectal (n = 25), cervical (n = 17) and lung (n = 25) tissues around the cancer were also examined.

RESULTSThe TP expression rate was 64.6% in gastric cancer, 67.9% in colorectal cancer, 80.9% in breast cancer, 82.1% in cervical cancer, and 63.8% in lung cancer, which was significantly higher than that in normal tissues (P = 0.0000). TP expression was positively correlated with MVD in gastric, colorectal, breast, and cervical cancers. The correlation was not statistically significant in lung cancer.

CONCLUSIONThis study indicates that TP overexpression in cancer may be associated with tumor angiogenesis.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; blood supply ; enzymology ; Colorectal Neoplasms ; blood supply ; enzymology ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Stomach Neoplasms ; blood supply ; enzymology ; Thymidine Phosphorylase ; metabolism ; Uterine Cervical Neoplasms ; blood supply ; enzymology

BACKGROUND/AIMS: Telomeres are simple repeat elements located at each chromosome end of eukaryotic cells. The main function of telomeres is to cap the chromosome end and protect it from enzymatic attack. Telomerase that facilitates the synthesis of telomere has been detected in not only cancer but also precancerous lesion. In this study, we compared the telomerase expression between low grade and high grade colorectal tubular adenoma. METHODS: Among thissues from forty eight patients with colorectal tubular adenoma (23 low grade and 25 high grade colorectal dysplasia), telomerase expressions were evaluated by immunohistochemical staining. RESULTS: We classified 48 patients into two groups by the extent of nuclei staining pattern. High telomerase expression was a group which showed staining nucleus pattern above 50% in tubular adenoma. Low telomerase expression was a group which showed staining pattern nucleus below 50%. Twelve in 25 high grade colorectal dysplasia showed high telomerase expression (48%). Only one in 23 low grade colorectal dysplasia showed high telomerase expression (4%). Telomerase expression was much higher in the tissues from the patients with high grade than in those with low grade colorectal dysplasia (p<0.05). CONCLUSIONS: Activation of telomerase may be related to the malignant potential in colorectal epithelial cells. Further studies are needed to define the role of telomerase in colorectal tumorigenesis.
Adenocarcinoma/*enzymology/pathology ; Adult ; Aged ; Colorectal Neoplasms/*enzymology/pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Telomerase/immunology/*metabolism

OBJECTIVETo investigate the expression of proline-rich tyrosine kinase-2 (Pyk2) in human primary colorectal carcinoma (CRC) and it's prognostic significance.

METHODSThe expression of Pyk2 was retrospectively examined with immunohistochemistry (IHC) in 108 tissues of primary CRC. The correlation of Pyk2 expression to prognosis and relevant clinical factors were analyzed.

RESULTSThe rate of Pyk2 low-expression in CRC was 56.5% (61/108). The expression of Pyk2 correlated significantly to the histological grade (P < 0.05) and the TNM stage (P < 0.05), while no correlation between Pyk2 expression and age, tumor size (P > 0.05). Patients with Pyk2 over-expression had significantly higher 5-year survival rate (66.0%) than those with Pyk2 low-expression (31.4%). Pyk2 expression, together with carcinoma histologic grade and TNM stage were prognostic factors to CRC on the multivariate analysis.

CONCLUSIONSPyk2 expression can be a prognostic factor to the CRC patients together with other predictors.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Focal Adhesion Kinase 2 ; metabolism ; Humans ; Male ; Middle Aged ; Prognosis

OBJECTIVETo investigate the expression of cancerous inhibitor of protein phosphatase 2A(CIP2A) in human colorectal cancer, and to examine the association of CIP2A expression with clinicopathology and prognosis.

METHODSCIP2A expression in colorectal cancer tissue microarray of 92 cases was detected by immunohistochemistry method.

RESULTSUp-regulated CIP2A expression was closely related with TNM staging, histological type, peritoneal seeding and liver metastasis (all P<0.05), but not related with gender, age, tumor location, CEA, family history and grade of differentiation. Overall survival rates of 1-, 3-, 5-, and 10-year in high CIP2A expression group were 97.1%, 71.4%, 59.2%, and 44.4% respectively, significantly lower than 98.2%, 85.7%, 80.3%, and 74.9% in low CIP2A expression group(P=0.021). Multivariate analysis showed that CIP2A was not an independent factor associated with prognosis(P=0.099, HR=1.982, 95%CI:0.879 to 4.469).

CONCLUSIONSUp-regulated CIP2A expression is closely related to clinicopathology of colorectal cancer. CIP2A may be used as a potential predictive marker of metastasis, prognosis and therapeutic target in colorectal cancer.

Autoantigens ; Biomarkers, Tumor ; metabolism ; Colorectal Neoplasms ; enzymology ; pathology ; Humans ; Immunohistochemistry ; Liver Neoplasms ; Membrane Proteins ; Neoplasm Staging ; Prognosis ; Protein Phosphatase 2 ; metabolism ; Survival Rate ; Tissue Array Analysis

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is downregulated during the early stages of colorectal carcinogenesis. The aim of the present study was to investigate the potential role of 15-PGDH in normal-appearing colorectal mucosa as a biomarker for predicting colorectal neoplasms. We obtained paired tumor and normal tissues from the surgical specimens of 32 sporadic colorectal cancer patients. mRNA expression of 15-PGDH was measured using a quantitative real-time PCR assay. We evaluated the association between 15-PGDH mRNA expression in normal-appearing mucosa, the presence of synchronous adenoma, and the cumulative incidence of metachronous adenoma. The relative 15-PGDH expression of normal-appearing mucosa in patients with synchronous adenoma was significantly lower than in patients without synchronous adenoma (0.71 vs 1.00, P = 0.044). The patients in the lowest tertile of 15-PGDH expression in normal-appearing mucosa were most likely to have synchronous adenoma (OR: 10.5, P = 0.024). Patients with low 15-PGDH expression in normal-appearing mucosa also demonstrated more advanced stage colorectal cancer (P = 0.045). However, there was no significant difference in the cumulative incidence of metachronous adenoma according to 15-PGDH mRNA expression in normal-appearing mucosa (P = 0.333). Hence, 15-PGDH in normal-appearing colorectal mucosa can be a useful biomarker of field effect for the prediction of sporadic synchronous neoplasms.
Aged ; Colorectal Neoplasms/*diagnosis/enzymology/pathology ; Down-Regulation ; Female ; Humans ; Hydroxyprostaglandin Dehydrogenases/genetics/*metabolism ; Intestinal Mucosa/*enzymology ; Male ; Middle Aged ; Neoplasm Staging ; Neoplasms, Multiple Primary/enzymology/pathology ; Neoplasms, Second Primary/enzymology/pathology ; Odds Ratio ; Predictive Value of Tests ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Risk Factors ; Tumor Markers, Biological/*metabolism

BACKGROUND/AIMS: Nuclear factor-kappa B p65 (NF-kappa B p65), nuclear factor-kappa B1 p50 (NF-kappa B p50) have been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. Recently, p38 mitogen-activated protein kinase (MAPK)/ NF-kappa B/ cyclin D1 signaling pathway has been shown to play an important part in the pathogenesis of human cancers. This study was designed to investigate the expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins in premalignant lesions of colon and colorectal adenocarcinoma. METHODS: Paraffin sections of 20 normal mucosa, 20 low-grade tubular adenoma, 20 high-grade tubular adenoma and 64 adenocarcinoma tissues were analysed immunohistochemically for the expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins. RESULTS: The expression of NF-kappa B p65, NF-kappa B p50, and p38 MAPK alpha proteins were significantly higher in adenocarcinoma tissue in comparison with that in normal mucosa, low-grade tubular adenoma, and high-grade tubular adenoma tissues. Expression of NF-kappa B p50 was more frequent in poorly differentiated histologic grade, presence of nodal metastasis, and advanced stage. Expression of p38 MAPK alpha protein was higher in advanced tumor stage, presence of nodal metastasis and advanced stage. Synchronous expression of NF-kappa B p65, NF-kappa B p50, p38 MAPK alpha, and cyclin D1 proteins were significantly higher in adenocarcinoma tissue. CONCULSIONS: With the increased expression of NF-kappa B p65, NF-kappa B p50, and p38 MAPK alpha proteins, p38 MAPK/ NF-kappa B/ cyclin D1 signaling pathway may play a role in the pathogenesis of colorectal carcinoma.
Adenocarcinoma/enzymology/*metabolism/pathology ; Colorectal Neoplasms/enzymology/*metabolism/pathology ; Cyclin D1/immunology/*metabolism ; Data Interpretation, Statistical ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa/metabolism ; Male ; Middle Aged ; NF-kappa B/immunology/*metabolism ; NF-kappa B p50 Subunit/immunology/metabolism ; Neoplasm Staging ; Precancerous Conditions/enzymology/*metabolism ; Transcription Factor RelA/immunology/metabolism ; p38 Mitogen-Activated Protein Kinases/*metabolism

OBJECTIVETo examine the association of 5-lipoxygenase (5-LOX) expression with clinicopathological factors in colorectal cancer.

METHODSImmunohistochemical stain was used to detect the 5-LOX expression in 52 resected specimens of colorectal cancer. The association between 5-LOX expression and clinicopathological factors was examined.

RESULTSThe positive rate of 5-LOX expression in 52 specimens of colorectal carcinoma was 73.1% (38/52). In 41 colorectal cancer specimens with lymph node metastasis, the positive rate of 5-LOX expression was higher than that in the specimens without metastasis (87.8% vs. 18.2%, P<0.05). The positive rate of 5-LOX expression in the specimens with deep infiltration (T3 and T4) was higher than that in the specimens with superficial infiltration (T1 and T2) (81.1% vs. 53.3%, P<0.05). The positive rate of 5-LOX expression in TNM stage III and IIII cancer was higher than that in stage I and II (79.5% vs. 53.8%, P<0.05). The positive rate of 5-LOX expression in cancers of poor differentiation and non-differentiation adenocarcinoma was higher than that of well and moderately differentiated cancer (100% vs. 50.0%, P<0.05). There were no significant differences of 5-LOX expression with tumor size,vascular invasion and peritoneal dissemination.

CONCLUSION5-LOX expression in colorectal carcinoma is closely associated with lymph node metastasis, infiltration depth, differentiation degree and TNM stage.

Adult ; Aged ; Aged, 80 and over ; Arachidonate 5-Lipoxygenase ; metabolism ; Colorectal Neoplasms ; enzymology ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging