Ectopic expression of B and T lymphocyte attenuator in gastric cancer: a potential independent prognostic factor in patients with gastric cancer.

It has been confirmed that B and T lymphocyte attenuator (BTLA; also known as CD272) is a novel co--inhibitory molecule that exhibits a critical role in restraining cell-mediated antitumor immunity. The present study aimed to investigate the expression and prognostic significance of BTLA in gastric adenocarcinoma. Immunohistochemical (IHC) staining was performed to investigate BTLA expression in gastric cancer tissues and normal mucosal tissues. In total, 123 pathologically confirmed specimens were obtained from stage IIIa gastric cancers. A correlation test, Kaplan-Meier curves, and a Cox proportional hazards regression model were used to analyze the data. No BTLA staining in the normal tissues was found, while BTLA-stained gastric carcinoma cells were detected in 75.6% (93/123) of the gastric cancer specimens. High expression levels of BTLA were detected in 31.7% (39/123) of the specimens, while low expression levels were detected in 68.3% (84/123) of the specimens. High BTLA expression levels were associated with shorter survival time, as confirmed by univariate and multivariate analyses. These findings provide a basis for the concept that high BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for the poor prognosis of patients with gastric cancer.

Clinicopathologic significance of putative stem cell marker, CD44 and CD133, in human gastric carcinoma.

BACKGROUND AND OBJECTIVES: CD44 and CD133 have been reported as putative stem cell markers. However, the clinicopathologic significance of CD44 and CD133 expression in patients with gastric carcinoma (GC) has not been clearly elucidated. METHODS: Immunohistochemistry (IHC) was performed to investigate the CD44 and CD133 expression in gastric carcinomas and normal mucosal tissues. Receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots, and Cox proportional hazards regression model were used to analyze the data. RESULTS: The highly expressed CD44 and CD133 were observed in 27/152 (17.7%) and 64/152 (42.1%) of GCs and in 4/60 (6.7%) and 15/60 (25.0%) normal gastric mucosal tissues, respectively (P < 0.05, Fisher's exact test). High expression of CD44 was significantly correlated with tumor poorer differentiation, presence of distant metastasis, advanced TNM stage, and tumor relapse; and high expression of CD133 was positively associated with tumor invasion depth, presence of distant metastasis and advanced TNM stage. More importantly, high-expressed CD44 and CD133 were both associated with shorter survival as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our study introduces high expression of CD44 and CD133 as adverse independent prognostic factors in GC patients. The combined CD44 and CD133 expression may become a useful tool for identifying patients with different clinical outcomes.

Overexpression of ZEB2 in peritumoral liver tissue correlates with favorable survival after curative resection of hepatocellular carcinoma.

BACKGROUND: ZEB2 has been suggested to mediate EMT and disease aggressiveness in several types of human cancers. However, the expression patterns of ZEB2 in hepatocellular carcinoma (HCC) and its effect on prognosis of HCC patients treated with hepatectomy are unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the methods of tissue microarray and immunohistochemistry (IHC) were utilized to investigate ZEB2 expression in HCC and peritumoral liver tissue (PLT). Receiver operating characteristic (ROC), spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. Up-regulated expression of cytoplasmic/nuclear ZEB2 protein was observed in the majority of PLTs, when compared to HCCs. Further analysis showed that overexpression of cytoplasmic ZEB2 in HCCs was inversely correlated with AFP level, tumor size and differentiation (P<0.05). Also, overexpression of cytoplasmic ZEB2 in PLTs correlated with lower AFP level (P<0.05). In univariate survival analysis, a significant association between overexpression of cytoplasmic ZEB2 by HCCs/PLTs and longer patients' survival was found (P<0.05). Importantly, cytoplasmic ZEB2 expression in PLTs was evaluated as an independent prognostic factor in multivariate analysis (P<0.05). Consequently, a new clinicopathologic prognostic model with cytoplasmic ZEB2 expression (including HCCs and PLTs) was constructed. The model could significantly stratify risk (low, intermediate and high) for overall survival (P = 0.002). CONCLUSIONS/SIGNIFICANCE: Our findings provide a basis for the concept that cytoplasmic ZEB2 expressed by PLTs can predict the postoperative survival of patients with HCC. The combined cytoplasmic ZEB2 prognostic model may become a useful tool for identifying patients with different clinical outcomes.

Secreted protein acidic and rich in cysteine (SPARC) is associated with nasopharyngeal carcinoma metastasis and poor prognosis.

BACKGROUND: The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC. METHODS: NPC tissue microarrays (TMAs) were constructed from Sun Yat-sen University Cancer Center (SYSUCC), another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT-PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs) induced by Bmi-1 (NPEC2 Bmi-1). The difference of SPARC expression in the cell lines was tested using a t-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. RESULTS: The expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi-1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (P = 0.002, P = 0.001). SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium. In addition, high level of SPARC positively correlated with the status of distant metastasis (P = 0.001) and WHO histological classification (P = 0.023). NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, P < 0.001), especially patients with advanced stage disease (log-rank, P < 0.001). Multivariate analysis suggested that the level of SPARC expression was an independent prognostic indicator for the overall survival of patients with NPC (P < 0.001). CONCLUSIONS: SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.

Decreased expression of Beclin 1 correlates with a metastatic phenotypic feature and adverse prognosis of gastric carcinomas.

BACKGROUND AND OBJECTIVES: Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The clinicopathological significance of Beclin 1 expression in patients with gastric carcinoma (GC) has not been yet elucidated. METHODS: Immunohistochemistry (IHC) was performed to investigate the Beclin 1 expression in GCs and normal mucosal tissues. Receiver operating characteristic curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: The highly expressed Beclin 1 was observed in 90/155 (58.1%) of GCs, in 24/60 (40.0%) adjacent mucosal tissues and in 13/30 (43.3%) of normal gastric mucosa tissues (P = 0.036). Decreased expression of Beclin 1 in cancer cells was significantly correlated with poor differentiation, nodal and distant metastasis, advanced TNM stage, and tumor relapse. More importantly, Decreased expression of Beclin 1 was associated with shorter survival as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our findings provide a basis for the concept that decreased expression of Beclin 1 in GC may be important in the acquisition of a metastatic phenotype, suggesting that decreased Beclin 1 expression, as examined by IHC, is an independent biomarker for poor prognosis of patients with GC.

No relationship between the distribution of mast cells and the survival of stage IIIB colon cancer patients.

BACKGROUND: Mast cells promote the progression of experimental tumors and might be a valuable therapeutic target. However, the relevant clinical evidence is still controversial. This study analyzed the relationship between the distribution of mast cells and the survival of patients with colon cancer to study whether mast cells contribute to tumor progression. MATERIALS AND METHODS: Ninety-three cases of pathologically confirmed primary cancer tissues matched with adjacent normal mucosa, metastases of regional-draining lymph nodes and regional-draining lymph nodes without metastases were collected from stage IIIB colon carcinoma patients between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. Tryptase-positive mast cells were counted. The relationships of the distribution of mast cells with clinicopathologic parameters and 5-year survival were analyzed. RESULTS: Although the mast cell count in the mucosa adjacent to the primary colon cancer was significantly higher than that in the stroma of the primary colon cancer, no difference in mast cell counts was observed between the stroma in lymph node metastasis and the lymph tissue adjacent to the metastasis. Additionally, the mast cell count in the regional-draining lymph node without the invasion of cancer cells was significantly higher than that in the stroma of lymph node metastasis and adjacent lymph tissue. However, none of those mast cell counts was related to 5-year survival. CONCLUSION: Although mast cell count varied with location, none of the mast cell counts was related to 5-year survival, suggesting that mast cells do not contribute to the progression of stage IIIB colon cancer.

miR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 proto-oncogene in human invasive breast cancer.

The microRNA miR-125b is dysregulated in various human cancers but its underlying mechanisms of action are poorly understood. Here, we report that miR-125b is downregulated in invasive breast cancers where it predicts poor patient survival. Hypermethylation of the miR-125b promoter partially accounted for reduction of miR-125b expression in human breast cancer. Ectopic restoration of miR-125b expression in breast cancer cells suppressed proliferation, induced G(1) cell-cycle arrest in vitro, and inhibited tumorigenesis in vivo. We identified the ETS1 gene as a novel direct target of miR-125b. siRNA-mediated ETS1 knockdown phenocopied the effect of miR-125b in breast cell lines and ETS1 overexpression in invasive breast cancer tissues also correlated with poor patient prognosis. Taken together, our findings point to an important role for miR-125b in the molecular etiology of invasive breast cancer, and they suggest miR-125b as a potential theranostic tool in this disease.

Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivo tumor growth.

INTRODUCTION: MicroRNAs (miRNAs) are a class of small non-coding RNAs (20 to 24 nucleotides) that post-transcriptionally modulate gene expression. A key oncomir in carcinogenesis is miR-21, which is consistently up-regulated in a wide range of cancers. However, few functional studies are available for miR-21, and few targets have been identified. In this study, we explored the role of miR-21 in human breast cancer cells and tissues, and searched for miR-21 targets. METHODS: We used in vitro and in vivo assays to explore the role of miR-21 in the malignant progression of human breast cancer, using miR-21 knockdown. Using LNA silencing combined to microarray technology and target prediction, we screened for potential targets of miR-21 and validated direct targets by using luciferase reporter assay and Western blot. Two candidate target genes (EIF4A2 and ANKRD46) were selected for analysis of correlation with clinicopathological characteristics and prognosis using immunohistochemistry on cancer tissue microrrays. RESULTS: Anti-miR-21 inhibited growth and migration of MCF-7 and MDA-MB-231 cells in vitro, and tumor growth in nude mice. Knockdown of miR-21 significantly increased the expression of ANKRD46 at both mRNA and protein levels. Luciferase assays using a reporter carrying a putative target site in the 3' untranslated region of ANKRD46 revealed that miR-21 directly targeted ANKRD46. miR-21 and EIF4A2 protein were inversely expressed in breast cancers (rs = -0.283, P = 0.005, Spearman's correlation analysis). CONCLUSIONS: Knockdown of miR-21 in MCF-7 and MDA-MB-231 cells inhibits in vitro and in vivo growth as well as in vitro migration. ANKRD46 is newly identified as a direct target of miR-21 in BC. These results suggest that inhibitory strategies against miR-21 using peptide nucleic acids (PNAs)-antimiR-21 may provide potential therapeutic applications in breast cancer treatment.

High expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients.

It has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3) is a crucial epigenetic process in tumorigenesis. However, the expression dynamics of H3K27me3 and its clinicopathological/prognostic significance in hepatocellular carcinoma (HCC) are unclear. In this study, immunohistochemical analysis (IHC) was used to examine protein expression of H3K27me3 in HCC tissues from two independent cohorts and corresponding nontumorous hepatocellular tissues by tissue microarray. The optimal cutpoint of H3K27me3 expression was assessed by the X-tile program. Our results showed that the cutpoint for high expression of H3K27me3 in HCCs was determined when more than 70% of the tumor cells showed positive staining. High expression of H3K27me3 was observed in 134 of 212 (63.2%) and 76 of 126 (60.4%) of HCCs in the testing and validation cohorts, respectively. Correlation analysis demonstrated that high expression of H3K27me3 in HCCs was significantly correlated with large tumor size, multiplicity, poor differentiation, advanced clinical stage and vascular invasion (P < 0.05). In addition, high expression of H3K27me3 in HCC patients was associated closely with shortened survival time, independent of serum α-fetoprotein levels, tumor size and multiplicity, clinical stage, vascular invasion and relapse as evidenced by univariate and multivariate analysis in both cohorts (P < 0.05). In different subsets of HCC patients, H3K27me3 expression was also a prognostic indicator in patients with stage II tumors (P < 0.05). Thus, these findings provide evidence that a high expression of H3K27me3, as detected by IHC, correlates closely with vascular invasion of HCCs and is an independent molecular marker for poor prognosis in patients with HCC.

Mast Cells in Adjacent Normal Colon Mucosa rather than Those in Invasive Margin are Related to Progression of Colon Cancer.

OBJECTIVE: Mast cells (MC) reside in the mucosa of the digestive tract as the first line against bacteria and toxins. Clinical evidence has implied that the infiltration of mast cells in colorectal cancers is related to malignant phenotypes and a poor prognosis. This study compared the role of mast cells in adjacent normal colon mucosa and in the invasive margin during the progression of colon cancer. METHODS: Specimens were obtained from 39 patients with colon adenomas and 155 patients with colon cancers treated at the Sun Yat-sen University Cancer Center between January 1999 and July 2004. The density of mast cells was scored by an immunohistochemical assay. The pattern of mast cell distribution and its relationship with clinicopathologic parameters and 5-year survival were analyzed. RESULTS: The majority of mast cells were located in the adjacent normal colon mucosa, followed by the invasive margin and least in the cancer stroma. Mast cell count in adjacent normal colon mucosa (MCC(adjacent)) was associated with pathologic classification, distant metastases and hepatic metastases, although it was not a prognostic factor. In contrast, mast cell count in the invasive margin (MCC(invasive)) was associated with neither the clinicopathlogic parameters nor overall survival. CONCLUSION: Mast cells in the adjacent normal colon mucosa were related to the progression of colon cancer, suggesting that mast cells might modulate tumor progression via a long-distance mechanism.

Nasopharyngeal extranodal NK/T-cell lymphoma, nasal type: retrospective study of 18 consecutive cases in Guangzhou, China.

OBJECTIVE: The aim of this study was to investigate the frequency and clinicopathologic features of nasopharyngeal extranodal NK/T-cell lymphoma, nasal type (NKTCL), as well as DNA sequence variation of Epstein-Barr virus (EBV) in neoplastic cells harboring in NKTCLs from Guangzhou district. MATERIALS AND METHODS: The clinical data of 18 unselected consecutive nasopharyngeal NKTCLs in one institution were reviewed retrospectively. Immunohistochemical staining and EBV-encoded RNAs (EBERs) in situ hybridization were applied. DNA extraction, polymerase chain reaction (PCR), nested PCR, and sequencing for analyzing the C-terminal and N-terminal regions of LMP1 gene as well as BamHI F fragment of EBV were applied in 16 available samples. RESULTS: NKTCLs accounted for 69.2% (18/26) of nasopharyngeal T- and NK-cell lineage non-Hodgkin lymphomas. In all, 10 out of 18 patients (55.56%) had cervical lymph node(s) involvement. The serum anti-EBV antibody level was elevated (VCA-IgA titer ≥1:40) in 6 of 12 available patients. Two major immunophenotypic subtypes, namely, TIA-1+/EBERs+/CD56+ (10 cases) and TIA-1+/EBERs+/CD56- (8 cases) could be recognized. Genotyping analysis revealed that 10 out of 13 cases (76.9%) of NKTCL were harbored with del-LMP1 [del-LMP1 (Gly335) variant 7 cases, del-LMP1 (Asp335) variant 3 cases]. XhoI-loss was shown in 8/11 cases (72.73%). BamHI "f" variant of Bam F fragment was shown only in 4/14 cases (28.57%).The most common combination was del-LMP1 (Gly335)/ XhoI-loss/F (6/9, 66.7%). CONCLUSIONS: The majority of nasopharyngeal T- and NK-cell lymphomas are NKTCL in Guangzhou district. The patients often have involvement of cervical lymph node(s) and an elevated level of serum anti-EBV antibodies. The CD56 expression rate seems lower than that found in sinonasal NKTCL. The most common EBV variant harboring in nasopharyngeal NKTCL seems somewhat different from that harboring in nasopharyngeal carcinoma in Guangzhou.

Epstein-Barr virus encoded latent membrane protein 1 regulates mTOR signaling pathway genes which predict poor prognosis of nasopharyngeal carcinoma.

BACKGROUND: The oncoprotein Epstain-Barr Virus (EBV)-encoded latent membrane protein1 (LMP1) modulates the pathological effects of the NF-kappaB, AP-1 and JAK/STAT pathways in nasopharyngeal carcinoma (NPC). METHODS: Microarray analysis was performed on the NPC cell line HONE1 stably transfected with a LMP1-expression plasmid or an empty vector. Based on assigned pathways analyzed using the KEGG database, the mTOR signaling pathway was selected for verification by quantitative RT-PCR. Western blot, RNA interference and immunofluorescence were used to determine the relationship between LMP1 and mTOR signing pathway genes, and their clinical significance to NPC. RESULTS: Our studies revealed that overexpression of LMP1 upregulated the mTOR signaling pathway, possibly through phosphorylation of AKT/mTOR/P70S6K/4EBP1 in the NPC cell lines HONE1 and 6-10B. Knockdown of LMP1 reduced expression of p-mTOR and p-4EBP1 in EBV-positive NPC cell line C666-1. In addition, LMP1 expression closely correlated with expression of p-mTOR, p-P70S6K and p-4EBP1 in NPC tumors. Expression of p-P70S6K, p-4EBP1 and LMP1, but not p-mTOR, significantly correlated with overall survival of NPC patients. However, only LMP1 was an independent prognostic factor. CONCLUSIONS: These results suggest that the mTOR signaling pathway is regulated by LMP1 expression in NPC. LMP1 and the genes in the mTOR pathway such as p-P70S6K and p-4EBP1 may be potential prognostic biomarkers.

The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer.

BACKGROUND: Although an abundance of evidence has indicated that tumor-associated macrophages (TAMs) are associated with a favorable prognosis in patients with colon cancer, it is still unknown how TAMs exert a protective effect. This study examined whether TAMs are involved in hepatic metastasis of colon cancer. MATERIALS AND METHODS: One hundred and sixty cases of pathologically-confirmed specimens were obtained from colon carcinoma patients with TNM stage IIIB and IV between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. The density of macrophages in the invasive front (CD68TFHotspot) was scored with an immunohistochemical assay. The relationship between the CD68TFHotspot and the clinicopathologic parameters, the potential of hepatic metastasis, and the 5-year survival rate were analyzed. RESULTS: TAMs were associated with the incidence of hepatic metastasis and the 5-year survival rate in patients with colon cancers. Both univariate and multivariate analyses revealed that the CD68TFHotspot was independently prognostic of survival. A higher 5-year survival rate among patients with stage IIIB after radical resection occurred in patients with a higher macrophage infiltration in the invasive front (81.0%) than in those with a lower macrophage infiltration (48.6%). Most importantly, the CD68TFHotspot was associated with both the potential of hepatic metastasis and the interval between colon resection and the occurrence of hepatic metastasis. CONCLUSION: This study showed evidence that TAMs infiltrated in the invasive front are associated with improvement in both hepatic metastasis and overall survival in colon cancer, implying that TAMs have protective potential in colon cancers and might serve as a novel therapeutic target.

Clinicopathologic features and Epstein-Barr virus infection status of Burkitt's lymphoma in Guangzhou district.

BACKGROUND AND OBJECTIVE: Sporadic Burkitt's lymphoma (sBL) is uncommon and its relation to Epstein-Barr virus (EBV) is unknown in China. This study was to investigate the clinical presentation, morphologic features, immunophenotype and EBV infection status of sBL in Guangzhou district, a prevalent area of EBV infection. METHODS: The clinical data of 21 sBL patients were reviewed. A panel of immunohistochemical staining was performed and EBV-encoded small RNAs (EBERs) in situ hybridization was applied to identify EBV infection. RESULTS: From January 2000 to October 2007, 21 cases(0.87%) of sBL were confirmed among 2416 cases of non-Hodgkin's lymphoma(NHL) in Sun Yat-sen University Cancer Center. Male to female ratio was 4.25 (17/4). The median age was 23 years. Of the 21 patients, 19 (90.48%) had lymph node(s) involvement; 16 (76.19%) had multiple sites involvement; 12 (57.14%) were at advanced stages (III/IV). The 2-year survival rate of 15 patients who received chemotherapy or resection plus chemotherapy was 56.00%. Twenty cases showed the prototypic morphology of sBL, and one was the variant of sBL with plasmacytoid differentiation. The main immunophenotype of these 21 sBLs was sIgM+/CD20+/CD10+/Bcl-6+/Bcl-2-[or Bcl-6+(>95%)/Bcl-2+(<10%)]/TdT-/Ki-67+ 100%. Of 20 detectable cases, 11 showed CD5 expression in a few (3%-20%) tumor cells. P53 was overexpressed in ten cases (47.62%). Six cases (28.57%) had EBV infection, with EBNA1 and EBERs expression, but not LMP1. There were no significant differences in morphology and immunophenotype between EBV-positive and EBV-negative cases. CONCLUSIONS: sBL is uncommon in Guangzhou district, mainly seen in boys and young men. Most patients had lymph node(s) involvement, showing similar morphology and immunophenotype as that of endemic BL. Type I EBV latent infection is associated with 28.57% of cases.

Expression and clinical significance of Wnt-1 and beta-catenin in nasopharyngeal carcinoma.

BACKGROUND AND OBJECTIVE: As signaling molecule and key component of Wnt/beta-catenin signaling pathway respectively, Wnt-1 and beta-catenin are abnormally expressed in several malignancies and correlate with poor prognosis. This study was to investigate the expression and clinical significance of Wnt-1 and beta-catenin in nasopharyngeal carcinoma (NPC). METHODS: The expression of Wnt-1 and beta-catenin in 111 specimens of NPC was detected by SP immunohistochemistry. Their correlations to relapse-free survival (RFS), metastasis-free survival (MFS) and progression-free survival (PFS) were analyzed. RESULTS: The high expression of beta-catenin was observed in 64 (57.7%) of the 111 cases. Its high expression rate was significantly higher in advanced NPC than in early stage NPC (63.1% vs. 40.7%, p = 0.041). The RFS, MFS and PFS were lower in high beta-catenin expression group than in low beta-catenin expression group (p < 0.05). Cox regression analysis demonstrated that beta-catenin was related to poor prognosis of NPC patients. The high expression of Wnt-1 was observed in 68 (61.3%) of the 111 cases, but its expression had no effect on RFS, MFS and PFS (p > 0.05). CONCLUSIONS: Wnt/beta-catenin signaling pathway may be activated abnormally in some NPC patients. beta-catenin may be a prognostic factor of NPC.

[Survivin and COX-2 expressions in giant cell tumor of bone and their relation to the prognosis].

OBJECTIVE: To investigate the expression of survivin and COX-2 in giant cell tumor of bone (GCT) and explore the prognostic factors for GCT. METHODS: The expressions of survivin and COX-2 in 39 GCT tissues of three Jaffe grades and 4 normal bone tissues were detected by immunohistochemical staining, and the data were analyzed in relation to the clinicopathological features of the patients. RESULTS: The expressions of survivin and COX-2 were significantly higher in the GCT tissues than in normal bone tissues (P<0.01). A positive correlation was found between survivin and COX-2 expressions and the pathological grade (P<0.01), but their expressions were not correlated to the patients' gender, age or surgical approaches (P>0.05). An obviously lowered recurrence rate was observed in patients with resection of the bone segment compromised by the tumor and subsequent bone grafting. Survivin and COX-2 were not independent risk factors of the prognosis of GCT. CONCLUSION: Survivin and COX-2 expressions may participate in the pathogenesis and development of GCT, but is not indicative of the prognosis.

Elevated expressions of survivin and VEGF protein are strong independent predictors of survival in advanced nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China. The China 1992 TNM staging system has been widely used for prognosis prediction of NPC patients in China. Although NPC patients can be classified according to their clinical stage in this system, their prognosis may vary significantly. METHOD: 280 cases of NPC with clinical follow-up data were collected and expressions of survivin and VEGF in tumor tissues were investigated by immunohistochemistry (IHC). Apoptosis index (AI) in 100 cases of NPC was detected by the TUNEL method. RESULTS: Expression of survivin and VEGF were significantly associated with TNM stage, T-stage and metastasis of NPC. The patients with survivin and VEGF over-expression presented lower 5-year survival rate, as compared to those of low-expression (42.32% vs. 70.54%, 40.1% vs. 67.8%, respectively, P < 0.05), especially in advanced stage patients (36.51% vs. 73.41%, 35.03% vs. 65.22%, respectively, P < 0.05). The 5-year survival rate in NPC patients with survivin and VEGF dual over-expression was significantly lower than that of patients with dual low-expression (18.22% vs. 73.54%, respectively; P = 0.0003). Multivariate analysis indicated that both survivin and VEGF over-expression in NPC tumor tissues were strong independent factors of poor prognosis in NPC patients. The mean AI in the 39 survivin low-expression cases was 144.7 +/- 39.9, which was significantly higher than that in 61 survivin over-expression cases (111.6 +/- 39.8) (T test, P < 0.05). CONCLUSION: Survivin and VEGF over-expression are independent prognostic factors for the patients with NPC. These results also suggest that tumor survivin and VEGF expressions are valuable prognostic markers for prognosis prediction in NPC patients.

[Expression and clinical significance of TGF-beta1 and its signaling pathway proteins in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Transforming growth factor beta (TGF-beta) has various biological functions, and plays important roles in cell proliferation, differentiation and apoptosis. This study was to investigate the expression and clinical significance of TGF-beta1 and its signaling pathway proteins (TGF-beta1 receptors TGFbetaRI and TGFbetaRII, cytoplasmic mediator Smad4) in nasopharyngeal carcinoma (NPC). METHODS: The expression of TGF-beta1, TGFbetaRI, TGFbetaRII, and Smad4 in 91 specimens of NPC was detected by SP immunohistochemistry. Their correlations to local relapse, distant metastasis and survival rate of the patients were analyzed. RESULTS: The positive rates of TGF-beta1, TGFbetaRI, TGFbetaRII and Smad4 were 69.2%, 73.6%, 62.6% and 72.5% in NPC. The differences in the positive rates of TGF-beta1 (0, 12.7%, 50.8%, and 36.5%) and TGFbetaRII (0, 15.8%, 54.4%, and 29.8%) among stageI, II, III and IV NPC were significant (P<0.05). However, there was no significant difference in the expression of TGFbetaRI and Smad4. The local relapse rate was significantly higher and 5-year overall survival rate was significantly lower in TGF-beta1-positive patients than in TGF-beta1-negative patients (22.2% vs. 3.6%, P<0.05û 63.5% vs. 82.1%, P<0.05). All the 4 proteins had no correlation to the distant metastasis of NPC (P>0.05). CONCLUSION: Autocrine TGF-beta1 exists in NPC patients, which is correlated to the local relapse and survival.

[Expression and clinical significance of survivin and PTEN in adrenal tumors].

BACKGROUND & OBJECTIVE: Since the histomorphology of adrenal tumor is very special, it is difficult to assess the malignancy of the tumors. This study was to explore the expression and clinical significance of Survivin and PTEN proteins in adrenal tumors. METHODS: The expression of Survivin and PTEN in 116 specimens of adrenal tumors, including 39 cases of cortex adenoma, 22 cases of cortex adenocarcinoma, 35 cases of pheochromocytoma, and 20 cases of malignant pheochromocytoma, were detected by LSAB immunohistochemistry. RESULTS: The positive rate of Survivin protein was 75.0%, and that of PTEN protein was 93.1%. The expression intensity of Survivin was correlated to that of PTEN in adrenal tumors (r=-0.486, P<0.05). The expression intensity of Survivin and PTEN in adrenal tumors were not related to patient's age, sex, tumor position, and so on (P>0.05). The expression intensity of Survivin was significantly lower in adrenal cortex adenoma than in adrenal cortex adenocarcinoma (P<0.05), and was significantly lower in pheochromocytoma than in malignant pheochromocytoma (P<0.05). The expression intensity of PTEN was related to the differentiation of adrenal tumor. The expression intensity of PTEN was significantly higher in adrenal cortex adenoma than in adrenal cortex adenocarcinoma (P<0.05), and was significantly higher in pheochromocytoma than in malignant pheochromocytoma (P<0.05). The expression of Survivin protein and PTEN protein was correlated to the prognosis of adrenal cortex adenocarcinoma and malignant pheochromocytoma: the higher the expression intensity of Survivin protein and the lower the expression intensity of PTEN protein, the worse the patient's prognosis (P<0.05). CONCLUSION: The expression of Survivin and PTEN proteins are closely related to the prognosis of adrenal tumors.

[Expression and clinical significance of uPA and PAI-1 in epithelial ovarian cancer].

BACKGROUND & OBJECTIVE: Recent researches showed that urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor (PAI)-1, play an important role in the invasion and metastasis of solid tumors. However, their correlations to epithelial ovarian cancer have seldom been reported. This study was to investigate the roles of uPA and PAI-1 in the invasion and metastasis of epithelial ovarian cancer, to clarify their localization and relationship with prognosis. METHODS: Immunohistochemistry was applied to examine the protein expression of uPA and PAI-1 in 80 specimens of epithelial ovarian cancer and 20 specimens of benign ovarian tumor. The correlations of their expression to the clinicopathologic characteristics and prognosis of the patients were analyzed. RESULTS: The positive rates of uPA and PAI-1 were significantly higher in epithelial ovarian cancer than in benign ovarian tumor (77.5% vs. 30.0%, P<0.001; 55.0% vs. 20.0%, P=0.005). uPA expression was correlated positively to PAI-1 expression in epithelial ovarian cancer (P=0.001). Higher positive rate of uPA was associated with greater metastatic tumor in the peritoneal cavity (P=0.038), but not associated with age, FIGO stage, histological type, pathologic grade, serum CA125 level, ovarian tumor size, and the size of residual tumor (P>0.05). Higher positive rate of PAI-1 was associated with early FIGO stage (P=0.022), but not associated with other parameters (P>0.05). Multivariate analysis showed that uPA was an independent factor for progression-free survival and overall survival, and PAI-1 was an independent factor for overall survival. CONCLUSION: Both uPA and PAI-1 are up-regulated in epithelial ovarian cancer, and might be used as markers to predict the prognosis of epithelial ovarian cancer patients.