[Expression of Tcf-4, MMP7 and Survivin in Colorectal Cancer and Its Clinical Significance].

OBJECTIVE: To explore the clinical and pathological significance and correlations among the xpressions of Tcf-4, MMP7 and survivin in colorectal cancer. METHODS: The expressions of Tcf-4, MMP7 and survivin mRNA in tumor tissues and adjacent normal mucosa from 50 colorectal cancer patients were detected by reverse transcription PCR (RT-PCR). The expressed proteins of Tcf-4, MMP7 and survivin were measured using mmunohistochemistry staining technique (Elivision) in 100 colorectal cancer samples and 60 normal mucosa tissue samples. We analyzed the correlations between those measurements and their associations with clinical and pathological characteristics. RESULTS: Positive expressions of Tcf-4, MMP7 and survivin mRNA were found in both cancer and adjacent mucosa tissues, despite a higher level of expression in the cancer tissues (P < 0.01). Expressed proteins were detected in cancer tissues of 69.00% (69/100) of those with a positive Tcf-4 expression, 77.00% (77/100) of those with a positive MMP7 expression, and 65.00% (65/100) of those with a positive survivin expression. Compared with cancer tissues, lower levels of protein expression were found in normal mucosa tissues [16.67% (10/60) for Tcf-4, 13.33% (8/60) for MMP7 and 15.00% (9/60) for survivin, P < 0.01]. The expressions of Tcf-4, MMP7 and survivin were all associated with lymphatic metastasis and Dukes staging (P < 0.05). MMP7 expression was associated with depth of tumor invasion (P < 0.05). Survivin expression was associated with tumor differentiation. The Spearman rank correlation analyses showed that protein expressions in colorectal cancer tissues in those with a positive Tcf-4 were correlated with those with a positive MMP7 (r = 0.302) and those with a positive survivin (r = 0.279) (P < 0.01), but not in those with a positive MMP7 and those with a positive survivin (r = 0.097, P > 0.05). CONCLUSION: The expression levels of Tcf-4, MMP7 and survivin are high in colorectal cancer, all being linked to lymph node metastasis and Dukes stages of patients. This suggests that they may be involved in the occurrence, development, malignant growth and clinical progression of colorectal cancer.

[Expression of secreted frizzled related protein 1, ß-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significances].

OBJECTIVE: To investigate the expression of secreted frizzled-related protein 1 (SFRP1), ß-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significance. METHODS: The expression of SFRP1, ß-catenin and E-cadherin mRNA and protein in tumor and pericancerous tissue samples from 60 cases of colorectal cancer was assayed by reverse-transcription PCR and immunohistochemistry, respectively. The correlation of their expression with clinicopathological factors of colorectal cancer was analyzed. RESULTS: In 52/60 cases the relative mRNA expression of SFRP1 in cancer tissue and pericancerous tissue was 0.4837±0.1532 and 0.7170 ±0.1830; for ß-catenin was 0.9293± 0.3705 and 0.6469±0.3166; and for E-cadherin was 0.5556±0.2535 and 0.9422±0.2372 (P<0.01), respectively. SFRP1 mRNA expression was associated with lymphatic metastasis (P<0.05). The positive rate of SFRP1 in colorectal cancer was 31.67% (19/60), and was significantly lower than that in pericancerous colorectal mucosa (75.00%, 45/60). No relationship between SFRP1 protein expression and clinical pathology was found. Abnormal expression rates of ß-catenin and E-cadherin in colorectal cancer were 75.00% (45/60) and 58.33% (35/60), respectively, which were significantly higher than that in pericancerous colorectal mucosa (1.67% and 6.67%), respectively. Abnormal ß-catenin and E-cadherin expression was associated with tumor differentiation, lymphatic metastasis and Duke's staging. SFRP1 protein expression was negatively correlated with ß-catenin and E-cadherin expression (r=-0.517, -0.442, Ps<0.01). CONCLUSION: Down-regulation of SFRP1 in colorectal cancer may cause abnormal Wnt signaling and induce abnormal ß-catenin and E-cadherin expression, indicating that SFRP1 might be involved in the development and progression of colorectal cancer, and could be a novel therapeutic target for colorectal cancer.

[The expression of KAI1 in gastric adenocarcinoma and relationship with angiogenesis/lymphangiogenesis].

OBJECTIVE: To seek good markers to predict invasion and metastasis of gastric adenocarcinoma (GAC). METHODS: Expression of Kangai 1 (KAI1), CD34, and D2-40 were examined by immunohistochemistry containing 145 specimens of GAC and 50 specimens of normal gastric tissue. Microvessel density (MVD) and lymph vessel density (LVD) were determined by the mean number of small CD34-positive or D2-40-positive vessels counted. And the relationship of KAI1, MVD and LVD, as well as the role of them on invasion, metastasis and prognosis in GAC were analyzed. RESULTS: The positive rate of KAI1, the median scores of MVD and LVD in normal gastric tissue and GAC tissue were 92.0%, (9.2 +/- 7.8)/LP, (7.5 +/- 7.6)/LP and 37.2%, (21.6 +/- 9. 1)/ LP, (22.6 +/- 12.7)/LP, respectively. And there was a significant different between the two groups (P < 0.05). The expression of KAI1, the scores of MVD and LVD were significantly related with pathologic-tumor-node metastasis (pTNM) stages, depth of invation and lymph node metastasis (all P < 0.05). There was a significant relationship between the expression of KAI1 and the scores of MVD or LVD. The survival rate of the KAI1-positive or KAI1-negative group was significantly different (P < 0.01); the survival rates were significantly lower in MVD > or = 22's group than that in MVD < 22's group, so was the same relationship between the LVD > or = 23's group and the LVD < 23's group (both P < 0.01). Cox regression analysis: pTNM stage, expression of KAI1, and the scores of MVD were independent factors of postoperative survival time in GAC (P < 0.05). CONCLUSION: The combined detection of KAI1, CD34, and D2-40 has an important role in predicting the progression and prognosis of GAC.

[Expression of Gal-3 and CD82/KAI1 proteins in non-small cell lung cancer and their clinical significance].

OBJECTIVE: To study the expression of galectin 3 (Gal-3) and CD82/KAI1 proteins in non-small cell lung cancer (NSCLC) and the correlation between their expression and clinical significance. METHODS: The expression of Gal-3 and CD82/KAI1 proteins was detected by immunohistochemistry in 160 specimens of NSCLC and 20 specimens of normal lung tissue. RESULTS: The positive rates of Gal-3 and CD82/KAI1 proteins in the NSCLC were 63.8% and 37.5%, respectively, the positive rates of Gal-3 and CD82/KAI1 proteins in the normal lung tissue were 25.0% and 95.0%, respectively, and there was a significant difference between the two groups (P < 0.01). The expression of Gal-3 and CD82/KAI1 proteins was significantly correlated with the grade of tumor, lymph node metastasis, and pathological-TNM stages (all P < 0.05). Spearman analysis showed that there was a negative correlation between expressions of Gal-3 and CD82/KAI1 in NSCLC (r = -0.732, P < 0.01). Overexpression of Gal-3 and low expression of CD82/KAI1 were related to poor prognosis: the survival rate was significantly lower in the positive Gal-3 group (survival time: 23.0 ± 17.5 months) than that in the negative group (survival time: 71.6 ± 21.6 months) (P < 0.01). The survival rates of the CD82/KAI1-positive group (survival time: 72.5 ± 19.5 months) and CD82/KAI1-negative group (survival time: 21.6 ± 16.1 months) were significantly different (P < 0.01). Multivariate analysis indicated that pTNM stage and positive expression of Gal-3 and CD82/KAI1 are independent prognostic factors of NSCLC (P < 0.01). CONCLUSIONS: The expression of Gal-3 and CD82/KAI1 may be related to the initiation, development and metastasis of NSCLC. Combined detection of Gal-3 and CD82/KAI1 has an important role in predicting the progression and prognosis of NSCLC.

Overexpression of MMP-1 and VEGF-C is associated with a less favorable prognosis in esophageal squamous cell carcinoma.

BACKGROUND: This study addresses the association of matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor-C (VEGF-C) expression in esophageal squamous cell carcinoma (SCC) with clinicopathologic characteristics in the patients. MATERIAL AND METHODS: We profiled the expression of MMP-1 and VEGF-C by cDNA microarray in 4 cases and by reverse transcription-polymerase chain reaction (RT-PCR) in 14 cases of esophageal SCC. Another 90 cases were reviewed by immunohistochemical examination of paraffin-embedded sections. RESULTS: Expression of MMP-1 and VEGF-C mRNA in normal esophageal tissue and tumor tissue was compared. Data were fully consistent with the results of RT-PCR. Immunohistochemistry showed that compared to the normal mucosa MMP-1 and VEGF-C protein expression was upregulated in both esophageal atypical hyperplasia (n = 16) and esophageal SCC. Depth of tumor invasion, lymph node metastasis, and clinical stage were directly associated with prognosis in all cases. Furthermore, median overall survival and disease-free survival were significantly shorter in patients with a higher expression of MMP-1 and VEGF-C than in patients with lower expression levels. CONCLUSION: We demonstrated that the expression of both MMP-1 and VEGF-C mRNA and protein was upregulated in esophageal SCC tissues. Protein expression was associated with progressive tumor stage and poor prognosis in patients with esophageal SCC.

Menetrier's disease and differential diagnosis: A case report.

BACKGROUND: Gastric mucosal hypertrophy, also known as Menetrier's disease (MD), is more common in men over 50 years of age, and the cause is unknown. The symptoms of the disease are atypical, mostly accompanied by hypoproteinemia and edema, and sometimes accompanied by symptoms such as epigastric pain, weight loss, and diarrhea. Most experts believe that the site of the disease is mainly located in the fundus of the stomach and the body of the stomach. We found that the site of the disease in this patient involved the antrum of the stomach. CASE SUMMARY: We introduced the case of a 24-year-old woman who had repeated vomiting for 5 d and was admitted to our hospital. After various examinations such as computed tomography and pathology in our hospital, the final diagnosis of the presented case is MD. The salient feature is that the mucosal folds in the fundus and body of the stomach are huge and present in the shape of gyrus. The greater curvature is more prominent, and there are multiple erosions or ulcers on the folds. The patient did not undergo gastric surgery and did not undergo re-examination. She is drinking Chinese medicine for treatment, and her vomiting and abdominal pain symptoms have improved. This disease is relatively rare in clinical practice, and it is easy to be misdiagnosed as gastric cancer, chronic gastritis and gastric lymphoma, etc. CONCLUSION: MD can occur in the antrum, it is necessary to raise awareness of the disease and reduce misdiagnosis.

[Comparative proteomic analysis of human gallbladder carcinoma].

OBJECTIVE: To find out potential molecular targets for gallbladder carcinoma diagnosis and treatment by analyzing and comparing the proteins expressed in human gallbladder carcinoma tissue and benign gallbladder tissue. METHODS: Proteomic analysis of 6 human gallbladder carcinoma tissues and 6 benign gallbladder tissues was carried out. Total proteins of the carcinoma tissue and benign gallbladder tissue were separated by two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were analyzed and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Immunohistochemistry was used to examine the expression of PEBP1 protein in an independent series of samples. RESULTS: Protein extracts of individual samples in each type of tissues were separated on two-dimensional gels. There were forty six differentially expressed proteins in the gallbladder carcinom tissues. Seventeen proteins were successfully identified by MS, in which nine proteins were overexpressed in tumors while the other eight proteins were underexpressed. The increased level of PEBP1 protein in gallbladder carcinoma was further confirmed by immunohistochemical analysis. CONCLUSION: Seventeen differentially expressed proteins were successfully characterized by comparative proteomic analysis. Those results may provide scientific foundation for screening the molecular biomarkers which can be used in diagnosis and treatment of gallbladder carcinoma, as well as to improve its prognosis and provide a new clue for carcinogenesis research of gallbladder carcinoma.

Inhibition of KiSS-1 on metastasis of nasopharyngeal carcinoma implant tumor in nude mice.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant neoplasm originated from the nasopharyngeal epithelium and is mainly prevalent in Southern China and Southeast Asia countries. KiSS-1 is an inhibitor of tumor metastasis in a range of cancers. METHODS: We establish a cell substrain of SUNE-1-5-8F (NPC cell line from humans) that trsnfected with lentiviral vectors carried with KiSS-1 gene and were selected by puromycin. A transplantation tumor animal model in BALB/c-nu mice was successfully established with a substrain that stably overexpressed KiSS-1. RESULTS: Our result showed that the size of transplantation tumor in the nude mice with KiSS-1 overexpression in transplantation tumor was not difference from the size of transplantation tumor in the controlled transplantation tumor mice. We detected metastatic tumor in lung but not in liver. Moreover, we also found that in the nude mice with KiSS-1 overexpression in transplantation tumor showed extremely fewer metastatic tumor in lung compared with the controlled transplantation tumor mice model. In conclusion, KiSS-1 may be beneficial for the inhibition of metastasis of human NPC. CONCLUSION: This study may throw light on the treatment of NPC and may help improve the prognosis of patients with NPC.

[Inhibition of gastric cancer cells growth in vitro by sulindac].

OBJECTIVE: To investigate the effect of sulindac on proliferation and apoptosis of human gastric cancer BGC-823 cells and its antineoplastic mechanisms. METHODS: Human gastric cancer BGC-823 cells were incubated with sulindac at various concentrations and for different times. Morphological changes of BGC-823 cells were observed under an inversion microscope. MTT colorimetric assay was used to examine the effect of sulindac on the proliferation of BGC-823 cells. Flow cytometry was used to determine the cell cycle distribution and apoptosis. Transmission electron microscopy was performed to examine cell apoptosis morphology. Immunohistochemical staining was used to detect the expressions of COX-2, bcl-2 and ki-67 in the cells. RESULTS: sulindac induced morphologic alterations in BGC-823 cells, inhibited cell proliferation, increased the proportion of cells in G0/G1 phase and decreased the proportion of cells in S phase, induced apoptosis of BGC-823 cells, and decreased expressions of COX-2, bcl-2, ki-67 in the cells. All the effects were in a time- and dose-dependent manner (P < 0.05). Some characteristic morphologic features of apoptosis were revealed by transmission electron microscopy. CONCLUSION: sulindac may inhibit the growth of gastric cancer BGC-823 cells in vitro and the anti-tumor mechanism may be related to changes in cell cycle distribution, induction of apoptosis and inhibition of expression of COX-2, bcl-2, and ki-67.

[Expressions of Slug, ZEB1 and KISS-1 in gastric adenocarcinoma and their clinical significance].

OBJECTIVE: To identify potential markers for predicting invasion, metastasis, and prognosis of gastric adenocarcinoma (GAC). METHODS: The expressions of Slug, ZEB1 and KISS-1 were detected immunohistochemically in 261 GAC tissues and 80 normal gastric tissues. RESULTS: The positivity rates of Slug, ZEB1, and KISS-1 in gastric tissues were 2.5%, 1.3%, and 87.5%, respectively, significantly different from the rates of 62.1%, 28.4%, and 41.1% in GAC tissues (P<0.05). The expression level of Slug was significantly correlated with the depth of invasion, lymph node metastasis, and pTNM stages; the positivity rates of both ZEB1 and KISS-1 were significantly correlated with the tumor grade, depth of invasion, lymph node metastasis and pTNM stages. Slug expression was positively correlated with ZEB1 expression, and KISS-1 expression was inversely correlated with Slug and ZEB1 expressions. Kaplan-Meier analysis showed that the overall survival time of patients with positive expressions of Slug and ZEB1 was significantly shorter than that of the negative patients, and the survival time of patients positive for KISS-1 was significantly longer than the negative patients. COX multivariate analysis showed that positive Slug, ZEB1 and KISS-1 protein expressions and pTNM stages were independent prognostic factors of GAC (P<0.05). CONCLUSION: The abnormal expressions of Slug, ZEB1 and KISS-1 may contribute to the tumorigenesis of GAC and are related with lymph node metastasis, pTNM stages, and prognosis of GAC. The combined detection of Slug, ZEB1, and KISS-1 expression has an important value in predicting the progression and prognosis of GAC.

Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry.

BACKGROUND: Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells (CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC. MATERIALS AND METHODS: Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses. RESULTS: In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD) was 21.7±11.1 in GAC tissues. There was a significantly difference between the positive and negative groups. There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (≥22) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05). CONCLUSIONS: VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC.

[Relation between helicobacter pylori L-form infection and tumor angiogenesis in human esophageal carcinoma].

OBJECTIVE: To investigate the correlation between helicobacter pylori L-form (Hp-L) infection in human esophageal carcinoma (EC) and tumor angiogenesis, and study the effect of Hp-L on the malignant biological behaviors of EC. METHODS: Hp-L was examined in 98 patients with EC and 30 controls by Gram stain, electronmicroscopic technique and immunohistochemical stain (ABC method). VEGF, p53 protein and microvessel density (MVD) were examined by immunohistochemical stain (SP method) with their relationship with the clinicopathologic factors analyzed. RESULTS: The positive rate of Hp-L was 60.2% in EC group. Two types of Hp-L were detected in the tissue of EC by electronmicroscopic technique, which lay in the outer or inner carcinoma cells. The positive rates of Hp-L, MVD, VEGF and p53 in the cancer group were significantly higher than those in control group (P < 0.005-0.001). The positive rates of MVD, VEGF and p53 in the Hp-L positive group of EC were significantly higher than those in Hp-L negative group (P < 0.005-0.001). The positive rate of Hp-L was correlated with MVD (r = 0.46, P < 0.01) and the expression of VEGF and p53 (r = 0.31, P < 0.01). The positive rate of Hp-L in the EC group was correlated with vessel invasion, depth of invasion, metastasis to the para-esophageal and distant lymph nodes except tumor size. CONCLUSION: Hp-L infection in EC is closely related with tumor angiogenesis and may be an important promoting factor in esophageal carcinoma growth, invasion and metastasis.

[Epstein-Barr virus infection and p16(INK4a) overexpression in gastric adenocarcinoma].

OBJECTIVE: To study Epstein-Barr virus infection and p16 protein abnormal expresson in carcinogenesis and progression of gastric adenocarcinomas (GAC). METHODS: Immunohistochemical staining SP method was used to detect the expression of LMP-1 and p16 in 97 cases of GAC. RESULTS: EBV LMP-1 and p16 protein were detected in 30.9% (30/97) and in 63.91% (62/97) cases of gastric adenocarcinomas respectively. There was no significant difference between EBV-positive and EBV-negative gastric carcinomas in sex, histologic type, depth of tumor invision, lymph node metastasis and clinical stages (P > 0.05); overexpression of p16 was associated with lymph node metastasis and clinical stages; no correlation was found between the expression of EBV LMP-1 and p16 protein. CONCLUSION: 1. EBV play a role in carcinogensis of GAC. 2. P16 gene abnormality is frequently involved in GAC and might be one of the important prognostic factors. 3. EBV infection and p16 alteration are two independent roles in GAC carcinogenesis.