Expression level of valosin-containing protein is strongly associated with progression and prognosis of gastric carcinoma.

PURPOSE: Valosin-containing protein (VCP; also known as p97) was shown to be associated with antiapoptotic function and metastasis via activation of nuclear factor kappa-B signaling pathway. In this study, association of VCP expression with recurrence of gastric carcinoma (GC), in which lymphatic vessels are the main route of spread, was examined. PATIENTS AND METHODS: VCP expression in 330 patients with GC (242 males and 88 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry, in which staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. RESULTS: Ninety-four (28.7%) patient cases showed level 1 and 233 patient cases (71.3%) showed level 2 VCP expression. Patients with level 2 expression showed higher rates of large tumor size (P <.0001), undifferentiated histologic subtype (P <.05), presence of vascular and lymphatic invasion (P <.0001 for both), presence of lymph node metastasis (P <.0001), deep tumor invasion (P <.0001), and poorer disease-free and overall survivals (P <.0001 for both) compared with those with level 1 VCP expression. Multivariate analysis revealed VCP expression level as an independent prognosticator for disease-free and overall survival. VCP level was an indicator for disease-free and overall survival in the early (pT1; P <.01 and P <.05, respectively) and advanced (pT2-4; P <.05 for both) group of pathologic tumor-node-metastasis system classification. CONCLUSION: The prognostic significance of VCP expression level in GC was demonstrated.     

Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis.

PURPOSE: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma. EXPERIMENTAL DESIGN: We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35-84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci. RESULTS: Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T(1-2) versus T(3-4), P < 0.05), presence or absence of venous invasion (P < 0.05), and tumor stage (I and II versus III and IV; P < 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P < 0.001) and poorer disease-free and overall survival (P < 0.01 and P < 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P < 0.05 and <0.01, respectively). CONCLUSIONS: A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.     

VCP蛋白表达与胃癌预后的相关性研究

目的：探讨VCP蛋白表达与胃癌预后的关系，确立VCP作为判断胃癌预后的独立因子作用。方法：在187倒胃癌组织手术标本中进行VCP的免疫组织化学染色，比较肿瘤细胞和正常血管内皮细胞VCP的表达，并结合肿瘤浸润、转移、预后等临床因素进行分析比较。结果：VCP的表达与胃癌的浸润、淋巴结转移相关，单变量分析中年龄、胃癌的浸润深度、脉管浸润、淋巴结转移及远处转移等因素显示与胃癌的预后相关（P〈0．05），多变量分析显示了VCP表达水平较肿瘤的分化、淋巴结浸润、转移与胃癌预后相关的危险系数高，故VCP的表达更能反映胃癌的预后。结论：VCP的表达是胃癌重要、独立的预后因子。     

Thymidylate synthase expression in colorectal cancer: a prognostic and predictive marker of benefit from adjuvant fluorouracil-based chemotherapy.

PURPOSE: We studied the prognostic value of thymidylate synthase (TS) expression in primary colorectal cancer (CRC) and the role of TS expression as a predictor of chemotherapeutic benefit in patients treated with adjuvant chemotherapy. PATIENTS AND METHODS: TS expression was immunohistochemically assessed on tumor sections from 862 patients with CRC Dukes' stages B and C enrolled onto randomized trials evaluating fluorouracil (5-FU)-based adjuvant chemotherapy. RESULTS: TS expression was an independent prognostic factor for disease-free (P =.05) and overall survival (P =.05). In the subgroup treated with surgery alone, TS was an independent prognostic factor for disease-free (P <.001) and overall survival (P =.001), whereas this was not the case in the subgroup of adjuvantly treated patients. Patients whose tumors expressed high TS levels had a tendency to improved outcome after adjuvant therapy (not significant). The group whose tumors expressed the highest TS grade, grade 3 (34% of the patients), had a significantly longer disease-free survival if they were treated with adjuvant therapy compared with surgery alone (multivariate analyses, P =.02), whereas patients whose tumors expressed low TS levels (28% of the patients) had an impaired outcome after adjuvant therapy (multivariate analyses: disease-free survival, P =.01; overall survival, P =.01). CONCLUSION: TS expression predicts for survival independent of Dukes' stage in patients with CRC treated with surgery alone. The study indicates that patients with high TS levels may benefit from adjuvant 5-FU-based chemotherapy. However, patients with low TS levels seem to have a worse outcome when treated with adjuvant chemotherapy.     

Expression level of valosin-containing protein (VCP) as a prognostic marker for gingival squamous cell carcinoma.

BACKGROUND: Valosin-containing protein (VCP) is associated with anti-apoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, association of VCP expression with prognosis of gingival squamous cell carcinoma (GSCC) was examined. PATIENTS AND METHODS: VCP expression in 74 patients with GSCC (34 males and 40 females) with ages ranging from 42 to 85 (median 66) years was evaluated by immunohistochemistry, in which staining intensity in tumor cells was categorized as either weaker (level 1) or equal to/stronger (level 2) than that in the endothelial cells. RESULTS: Twenty-four (32.4%) cases showed level 1 and 50 (67.6%) level 2 VCP expression. Patients with level 1 GSCC showed a significantly better 5-year survival rate than those with level 2 GSCC (5-year overall survival: 100% versus 84.9%, P < 0.05). Multivariate analysis revealed VCP expression level, lymph node metastasis and pT(TNM) to be independent factors for overall survival. Patients with GSCC at stages I and II showed favorable prognosis regardless of VCP expression status, whereas at stages III and IV, patients with level 1 VCP expression showed better survival rates than those with level 2 expression. CONCLUSION: Prognostic significance of VCP expression level in GSCC was demonstrated.     

Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort.

PURPOSE: This study aims to clarify the clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The clinicopathologic features of 5-year survivors and disease-free survivors were elucidated in a cohort of 230 patients prospectively observed for > 5 years (64 to 192 months) after curative resection of HCC. RESULTS: The incidence of 5-year overall and disease-free survivors were 37% (85 of 230) and 20% (45 of 230), respectively. Clinicopathologic features associated with 5-year survivors included female sex (P =.024), preoperative serum albumin > or= 40 g/L (P =.033), AST < 50 u/L (P =.001), tumor < 5 cm (P =.001), solitary tumor (P =.035), encapsulated tumor (P =.021), no venous invasion (P =.001), no microsatellite nodule (P =.001), and early pathologic tumor-node-metastasis (pTNM) stage (I or II, P <.001). Features favoring 5-year disease-free survivors were preoperative serum AST < 50 u/L (P =.007), tumor < 5 cm (P =.005), encapsulated tumor (P =.007), no venous invasion (P <.001), no microsatellite nodule (P =.001), and early pTNM stage (I or II, P <.001). By multivariate analysis, pTNM stage was the only significant predictive factor for both overall and disease-free survival. CONCLUSION: This study shows that long-term disease-free survival > 5 years after resection of HCC can be achieved in patients with favorable tumor characteristics. Early pTNM stage was the most reliable predictor of both long-term overall and disease-free survivors.     

Expression Level of Valosin Containing Protein is Associated with Prognosis of Primary Orbital MALT Lymphoma

Objective: To investigate whether the expression level of valosin-containing protein (VCP) is correlated withthe prognosis of primary orbital mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: VCP expressionin 58 samples from primary orbital MALT lymphoma patients was determined by immunohistochemisty usingmonoclonal antibodies. Correlations between VCP expression level and prognosis were clarified by statisticalanalysis. Results: It was found that the percentage of VCP positive cells in samples of primary orbital MALTlymphoma ranged from 32% to 95%. The samples were divided into two groups (level 1 and level 2) accordingto the median value (45%) of the percentage of VCP positive cells. It was found that the expression level of VCPwas significantly correlated with recurrence (P=0.003) and tumor size (P=0.008). At the same time, the 5-yeardisease-free and overall survival rate of patients of level 1 was significantly better than that of level 2 (P=0.001;P=0.032). There was no observed correlation between the expression level of VCP and other clinical features.Conclusion: VCP could be a useful marker for predicting the prognosis of primary orbital MALT lymphoma.     

Differential Expression of IQGAP1/2 in Hepatocellular Carcinoma and its Relationship with Clinical Outcomes

Purpose: To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes. Methods: IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis. Results: IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (Ⅲ and Ⅳ, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (Ⅲ and Ⅳ, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2- tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189). Conclusion: Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.     

Prognostic significance of CD100 expression in soft tissue sarcoma

BACKGROUND: CD100, a class IV semaphorin, promotes angiogenesis, invasive growth, proliferation, and antiapoptosis of cancer cells in vitro. The expression of CD100 in soft tissue sarcoma (STS) and its correlation with clinicopathologic factors and prognostic significance were evaluated. METHODS: Expression levels of CD100 in patients with localized STS were evaluated immunohistochemically on paraffin-embedded sections from 81 patients, including 47 men and 34 women with a median age of 54 years. Staining intensity was categorized into weaker than (level 1) or equal to that of lymphocytes with a rate of <10% stained tumor cells (level 2) or >10% stained tumor cells (level 3). Ki-67 staining was performed in parallel. RESULTS: Forty-two tumors (52%) had level 1 CD100 expression, 18 tumors (22%) had level 2 CD100 expression, and 21 tumors (26%) had level 3 CD100 expression. Tumors that had level 2 and 3 CD100 expression were correlated significantly with higher mitotic count, cellularity, ratio of necrosis, and Ki-67 labeling index (LI) compared with tumors that had level 1 CD100 expression. There was no correlation between CD100 expression and other characteristics. Among the 3 levels of CD100 expression, higher expression levels were correlated with poorer overall and disease-free survival. Multivariate analysis revealed that CD100 expression (levels 1 and 2 vs level 3) and tumor size (5 cm) were independent prognosticators for overall survival (P < .05 for both), and CD100 expression (levels 1 and 2 vs level 3) was an independent prognosticator for disease-free survival (P < .05). CONCLUSIONS: The results from this study indicated the demonstrated prognostic significance of CD100 expression in STS.     

RELATIONSHIP OF THE EXPRESSION OF MDR1 GENE PRODUCT IN HEPATO CELLULAR CARCINOMA TO INVASION AND METASTASIS

ＩＮＴＲＯＤＵＣＴＩＯＮＰｇｌｙｃｏｐｒｏｔｅｉｎ（Ｐｇｐ），ｔｈｅｐｒｏｄｕｃｔｏｆｔｈｅｍｕｌｔｉｄｒｕｇｒｅｓｉｓｔａｎｃｅ（ＭＤＲ１）ｇｅｎｅ，ｉｓａ１７０Ｋｄａｍｅｍｂｒａｎｅｐｒｏｔｅｉｎｒｅｓｐｏｎｓｉｂｌｅｆｏｒｐｕｍｐｉｎｇ...     

Decreased Expression of LKB1 Correlates with Poor Prognosisin Hepatocellular Carcinoma Patients Undergoing Hepatectomy

Aim: To study any correlation of LKB1 expression with prognosis in hepatocellular carcinoma (HCC) cases.Methods: A total of 70 HCC patients and 20 primary intrahepatic stone patients in the first affiliated hospital ofWenzhou Medical College were enrolled in this study. LKB1 expression was detected by immunohistochemistry.Patients were followed-up and prognostic factors were evaluated. Result: LKB1 expression was decreased in theHCC samples. Loss of LKB1 expression in HCC was significantly related to histologic grade (P=0.010), vascularinvasion (P=0.025) and TMN stage (P=0.011). Patients showing negative LKB1 expression had a significantlyshorter disease-free and overall survival than those with positive expression (P = 0.001, P=0.000, respectively).Multivariate Cox regression analysis indicated that LKB1 expression level was an independent factor of survival(P = 0.033). Conclusion: HCC patients with decreased expression LKB1 have a poor prognosis. The loss of LKB1expression is correlated with a lower survival rate.     

肝癌患者围手术期外周血甲胎蛋白mRNA表达与术后复发的关系

背景与目的:甲胎蛋白(alpha-fetoprotein,AFP)mRNA是检测肝癌患者外周血中癌细胞常用的标志物。本研究探讨肝癌患者围手术期的外周血中AFPmRNA表达与术后复发的关系。方法:应用巢式PCR和Taq Man MGB探针法PCR定量技术,检测56例肝细胞癌患者术前和术后外周血、15例良性肝占位性病变合并肝硬化患者外周血以及30例健康志愿者外周血AFP mRNA的表达情况。结果:肝癌患者术前外周血AFP mRNA的阳性率为42.9%(24/56),高于良性肝占位合并肝硬化患者的13.3%(2/15)和健康对照的10.0%(3/30),其差异均有统计学意义(P=0.035,P=0.002)。术前AFP mRNA的表达与肿瘤有无肉眼及镜下血管侵犯的相关性有统计学意义(P=0.029,P<0.001)。AFP mRNA阴性患者1、2、3年生存率及无瘤生存率均比AFP mRNA阳性患者术后高(P=0.003,P=0.039)。Cox多因素分析结果显示术前外周血AFP mRNA阳性是预测术后复发的独立因素(P=0.018)。术后患者外周血AFP mRNA的阳性率为37.5%(21/56),术后AFP mRNA的表达与患者各项临床病理特征、预后以及术前AFP mRNA水平的相关性均无统计学意义。结论:肝癌患者术前外周血中AFP mRNA阳性者比AFP mRNA阳性者肿瘤侵袭性更强,术后可能更易复发。     

Expression of hepatoma-derived growth factor is correlated with lymph node metastasis and prognosis of gastric carcinoma.

PURPOSE: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined. PATIENTS AND METHODS: HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry. Samples with >90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1. RESULTS: One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001 for both) compared to those with level 1 expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival. CONCLUSION: HDGF expression level was shown to be a prognostic factor for gastric carcinoma.