Objective: To investigate the dynamic expression pattern of carcinoembryonic Wnt3a and its early monitoring value using a hepatocellular carcinoma model. Methods: Forty-eight Sprague Dawley (SD) rats were fed with pellet feed containing 2-acetylaminofluorene (2-AAF, 0.05%) to induce hepatocarcinogenesis, and control rats were fed a pellet diet. Liver tissue and blood samples were collected every two weeks. Liver tissues were pathologically examined using HE staining and grouped. The gene and Wnt3a mRNA expression were analyzed by genome-wide microarray. The expression and distribution of Wnt3a in liver tissue were analyzed by immunohistochemistry. Wnt3a concentration in liver tissue and serum was quantified by enzyme-linked immunosorbent assay. Statistical methods such as χ² test, Mann-Whitney test and analysis of variance were used to analyze the differences between groups. Results: According to the pathological examination results, the rat livers were divided into four groups: control, hepatocyte degeneration, precancerous lesions and hepatocellular carcinoma. Genome-wide expression profiling analysis and comparison with the control group revealed that 268 and 312 genes were up-regulated and 57 and 201 genes were down-regulated in the precancerous and cancerous group when signal logarithm ratio (SLR) was >8 log₂^cy5/cy3, and these significantly altered genes mainly involved in cell proliferation, signal transduction, tumor metastasis, and apoptosis. The expression of Wnt3a at mRNA level was significantly increased in all stages of cancer induction, including degeneration group (1.15±0.24, q=8.227), precancerous group (1.85±0.18, q=12.361) and cancerous group (2.59±0.55, q=18.082). Compared with the control group (0.25±0.11, F=121.103, P<0.001), the degeneration group, the precancerous group and the liver cancer group were up-regulated by 4.6, 7.4 and 10.4-folds, respectively. Immunohistochemistry showed that compared with the control group, the positive rate of Wnt3a in the degeneration group was 66.7% (12/18, χ²=10.701, P=0.001), and both the precancerous and liver cancer groups were positive (9/9, χ²=17.115, P<0.001). Wnt3a expression was gradually increased in liver and blood samples during the process of carcinogenesis, and the difference between two groups was statistically significant (F=176.711, P<0.001). Wnt3a overexpression was secreted into blood stream via cancerous liver tissue, and there was a linear correlation between Wnt3a levels in blood and liver samples (r=0.732, P<0.001). Conclusions: Wnt3a overexpression is closely related with hepatocellular carcinogenesis, and thus may become a new monitoring marker.
Rats ; Animals ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Rats, Sprague-Dawley ; Carcinogenesis/metabolism* ; 2-Acetylaminofluorene ; RNA, Messenger/metabolism* ; Precancerous Conditions

Breast ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; diagnosis ; metabolism ; pathology ; Female ; Humans ; Hyperplasia ; metabolism ; pathology ; Keratin-5 ; metabolism ; Keratin-6 ; metabolism ; Precancerous Conditions ; diagnosis ; metabolism ; pathology ; Stem Cells ; metabolism ; pathology

Animals ; Colonoscopy ; methods ; Colorectal Neoplasms ; pathology ; Disease Models, Animal ; Heterogeneous-Nuclear Ribonucleoproteins ; metabolism ; Precancerous Conditions ; pathology ; Rodentia

OBJECTIVETo investigate the diagnostic applications of endometrial intraepithelial neoplasia (EIN), and the expression of PTEN in endometrial lesions.

METHODSFifty-one cases of endometrial lesions were enrolled in this study. Using diagnostic criteria of EIN, the diagnosis were made and compared with the original results. Immunohistochemistry for PTEN was performed in all cases.

RESULTSTwo cases of simple hyperplasia originally diagnosed were reclassified as EIN. Three cases with atypia originally diagnosed showed no EIN pattern. PTEN deletion rates were 50.0%, 50.0%, 66.7% and 81.8% in proliferative endometrium, benign hyperplasia, EIN and endometrial carcinoma, respectively.

CONCLUSIONSDiagnosis of EIN is applicable and its morphology and diagnostic criteria are different from the classical one (WHO94) for endometrial hyperplasia. Detection of PTEN deletion by immunohistochemistry is useful in identifying EIN, but cannot be used as an ultimate confirming factor.

Adult ; Aged ; Carcinoma, Endometrioid ; metabolism ; pathology ; Endometrial Hyperplasia ; metabolism ; pathology ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Middle Aged ; PTEN Phosphohydrolase ; metabolism ; Precancerous Conditions ; metabolism ; pathology ; Young Adult

Humans ; Infant ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Male ; Mucin-1 ; metabolism ; Nephrectomy ; Precancerous Conditions ; metabolism ; pathology ; surgery ; Vimentin ; metabolism ; WT1 Proteins ; metabolism ; Wilms Tumor ; metabolism ; pathology ; surgery

OBJECTIVETo detect the expression of PTEN, PIP3 and cyclin D1 in oral squamous cell carcinoma and precancerous lesions and analyze their correlation.

METHODSImmunohistochemistry SP method was used to detect the expression of PTEN, PIP3 and cyclin D1 in 63 cases of oral squamous cell carcinoma, 29 cases of simple hyperplasia, 33 cases of dysplasia, and 25 cases of normal oral mucosa.

RESULTSThe negative or low expression of PTEN in oral squamous cell carcinoma was 25%, which was remarkably lower than that in other groups. The positive expression of PIP3 in simple hyperplasia, dysplasia and oral squamous cell carcinoma was 66%, 64%, and 76% respectively, which were much higher than those in normal oral mucosa. The positive expression of cyclin D1 in oral squamous cell carcinoma was 49%, which was significantly higher than that in other groups. The negative correlation between PTEN with PIP3, cyclin D1 and the positive correlation between PIP3 and cyclin D1 were observed.

CONCLUSIONSPTEN may play a role in the oncogenesis of oral squamous cell carcinoma, and PTEN may down-regulate the expression of PIP3, and then down-regulate the expression of cyclin D1, which leads to the suppression of cell growth.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Cyclin D1 ; metabolism ; Genes, Tumor Suppressor ; Humans ; Mouth Neoplasms ; metabolism ; pathology ; PTEN Phosphohydrolase ; metabolism ; Precancerous Conditions ; metabolism ; pathology

OBJECTIVETo evaluate the expression of p27 protein in oral precancerous lesions and oral squamous cell carcinoma (OSCC).

METHODSImmunohistochemistry was used to detect p27, p53, murine double minute (MDM2) and p21 protein expression in a series of 13 specimens with simple hyperplasia, 44 with dysplasia and 48 with OSCC. An attempt was made to correlate the protein levels with clinicopathologic parameters and Ki-67 protein levels.

RESULTSPositive p27 staining was present in 79.55% of the dysplasia samples, as well as in 81.25% of the OSCC samples. p27 protein overexpression in OSCC group was significantly higher than that in leukoplakia group (P < 0.001). The extent of p27 expression was positively associated with Ki-67 expression (P < 0.001). Cases with p27 overexpression displayed concurrent expression of p53 and/or MDM2 (P = 0.034) in OSCC group.

CONCLUSIONSp27, p53, MDM2 and p21 may all play important roles in the genesis of OSCC. The alterations of one or more cell cycle regulators are prevalent in oral premalignant lesions and OSCC and the regulators can regulate each other.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Cycle Proteins ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Humans ; Immunohistochemistry ; Mouth Neoplasms ; metabolism ; pathology ; Precancerous Conditions ; metabolism ; pathology

OBJECTIVETo study the syndrome evolution law of Chinese medicine (CM) in the patients with gastric mucosal dysplasia.

METHODSThree hundred and twenty four gastric mucosal dysplasia patients with deficiency and excess correlation syndromes were enrolled by a multi-center collaboration for two years' clinical follow-up to detect the levels of tumor supplied group of factors (TSGF) and carcino-embryonic antigen (CEA).

RESULTSAmong the 324 cases, 29 cases turned cancer in the two years, and the canceration rate was 9.0%. The three syndromes with higher canceration rate were the damp-heat accumulating Wei syndrome concurring or combining with asthenia-cold in Pi and Wei syndrome for 16.7%; stagnation in Wei collaterals syndrome concurring or combining with asthenia of both qi and yin syndrome for 13.2%; stagnation of Gan and Wei qi syndrome concurring or combining with asthenia-cold in Pi and Wei syndrome for 8.0%, respectively. Among the three syndromes, the highest level of TSGF occurred in the former two syndromes. In the half year before carcinogenesis, the syndromes of the patients took on deficiency and excess concurrent syndromes, and the deficiency syndromes involving the qi and blood deficiency syndrome and the Shen deficiency syndrome accounting for 48.0%.

CONCLUSIONSGastric mucosal dyspalsia canceration syndromes took on the polymorphism of excess and deficiency concurrent syndromes and had the characteristics of deficiency syndromes involving qi and blood deficiency syndrome and Shen-yin-yang deficiency syndrome.

Biomarkers, Tumor ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Gastric Mucosa ; metabolism ; pathology ; Gastroscopy ; Humans ; Hyperplasia ; Medicine, Chinese Traditional ; Precancerous Conditions ; metabolism ; pathology ; Stomach Neoplasms ; diagnosis ; pathology ; Syndrome

OBJECTIVETo investigate the changes of cytokeratin 19 during oral carcinogenesis.

METHODS53 specimens including normal oral mucosa, oral epithelial hyperplasia, oral epithelial dysplasia and oral squamous cell carcinoma were investigated by immunohistochemistry, SDS-PAGE and Western blotting.

RESULTSCK19 was detectable in suprabasal cell layers in epithelial dysplasia and in oral cancer, especially in poor-differentiated cancerous cells. With the lesions getting worse, the positive rate, the intensity and the constituent ratio of CK19 raised significantly.

CONCLUSIONSThe results suggest that the CK19 expression in suprabasal cell layers of oral mucosa can be used as a marker of diagnosis of oral precancerous lesions and CK19 expression is the initial events during oral carcinogenesis.

Adult ; Aged ; Blotting, Western ; Female ; Humans ; Immunohistochemistry ; Keratins ; analysis ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; pathology ; Mouth Neoplasms ; metabolism ; pathology ; Precancerous Conditions ; metabolism ; pathology

Animals ; Apoptosis ; Azoxymethane ; Colorectal Neoplasms ; chemically induced ; metabolism ; pathology ; Cytoskeletal Proteins ; metabolism ; Precancerous Conditions ; chemically induced ; metabolism ; pathology ; Rats ; Rats, Inbred F344 ; Trans-Activators ; metabolism ; beta Catenin