Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer

BACKGROUND: Although the TNM stage is the most important prognostic factor for gastric cancer, there is a need for new prognostic and predictive factors, because the prognosis varies among patients of the same stage. The purpose of this study was to clarify the relationship of p53, nm23, proliferating cell nuclear antigen (PCNA) and c-erbB-2 with the clinicopathological parameters and the survival results. METHODS: For 841 patients who had undergone gastrectomy for gastric cancer at Seoul National University Hospital from July 1996 to December 1997, the expression levels of p53, nm23, PCNA and c-erbB-2 in gastric cancer tissues were examined immunohistochemically. Also, the clinicopathological parameters such as gender, age, operation type, TNM stage and size of the tumor, histology and Lauren classification were analyzed retrospectively. RESULTS: There were 568 males and 273 females (2.07:1) with a mean age of 56 years (range:25-82 years). The percentages of positive expression of p53, nm23 and c-erbB-2 were 43, 74 and 17%, respectively; 59% of tumors expressed PCNA index > or =50. p53 expression was associated with age, gender, tumor size, histology, Lauren classification, stage, nm23 expression, PCNA index >or =50 and c-erbB-2 expression. nm23 expression was associated with age, tumor size, Borrmann type, histology, Lauren classification and stage. PCNA index > or =50 was associated with age, gender, tumor size, Borrmann type, histology, Lauren classification and c-erbB-2 expression. c-erbB-2 expression was associated with gender, Borrmann type, histology and Lauren classification. p53 and nm23 were related with poor prognosis in univariate analysis. nm23 was related with poor prognosis of stage III and diffuse-type gastric cancer in univariate subgroup analysis. However, in a multivariate study, these prognostic impacts were not maintained. CONCLUSION: The expression of p53 and nm23 seems to be related with poor prognosis of gastric cancer patients who have undergone gastrectomy. However, the prognostic significance was not revealed by a multivariate analysis.     

Prognostic significance of CEA, CA 19-9 and CA 72-4 preoperative serum levels in gastric carcinoma.

The prognostic value of preoperative serum levels of CEA, CA 19-9 and CA 72-4 tumor markers was investigated in 153 patients resected for gastric cancer. The positivity rates for CEA, CA 19-9 and CA 72-4 were 20.9, 34.6 and 28.1%, respectively. Multiple logistic regression analysis for positive levels of tumor markers indicates that CEA positivity is significantly related to the depth of invasion (p < 0.005) and the presence of distant metastasis (p < 0. 05), CA 19-9 positivity is related to nodal involvement (p < 0.05) and the depth of invasion (p < 0.05), whereas CA 72-4 positivity is influenced by tumor size (p < 0.005) and noncurative surgery (p < 0. 05). Positive levels of each tumor marker were associated with a worse prognosis if compared with negative cases using univariate analysis. Multivariate analysis of curatively resected cases identified depth in gastric wall (p < 0.0001), nodal status (p < 0. 0005), and tumor location in the upper third (p < 0.05) as significant prognostic variables; CEA, CA 19-9 and CA 72-4 serum positivity did not reach statistical significance. However, when the positivity of the three markers was associated, a p value < 0.05 was observed. The analysis of survival curves stratified by tumor stage revealed that marker positivity significantly affects survival in stages I, II and IV (p < 0.05). The combined assay of CEA, CA 19-9 and CA 72-4 preoperative serum levels provides additional prognostic information in patients resected for gastric cancer; patients with preoperative positivity for one of these tumor markers should be considered at high risk of recurrence even in early stages of gastric carcinoma.     

Multimarker phenotype predicts adverse survival in patients with lymph node-negative colorectal cancer

BACKGROUND: The heterogeneity of stage II colon cancer underlines the need for identifying high-risk, lymph node-negative patients. The objective of this study was to define a multimarker prognostic model of 5-year survival in patients with lymph node-negative, mismatch repair (MMR)-proficient colorectal cancer (CRC). METHODS: Immunohistochemistry for 13 tumor markers was performed on 587 lymph node-negative, MMR-proficient CRC samples by using a tissue microarray. Immunoreactivity was evaluated semiquantitatively. A receiver-operating characteristic-based approach was used to detect clinically relevant tumor markers and to determine cutoff scores for tumor positivity. Univariate and multivariate analyses stratified by pathologic T3 (pT3) or pT4 tumor classification were performed. RESULTS: In univariate analysis, the absence of CD8+ tumor infiltrating lymphocytes (TILs) (P < .001), loss of p27 (P = .006), positive urokinase-type plasminogen activator (uPA) expression (P = .002), and positive uPA receptor (uPAR) expression (P = .037) were associated with an adverse prognosis. In multivariate analysis, CD8 (P = .001), p27 (P = .031), and uPA (P = .014) were independent prognostic factors. The multimarker phenotype of negative CD8, loss of p27, and positive uPA expression led to significantly worse survival compared with all other combinations of these features. Stratified by pT3 or pT4 stage, CD8 (P = .006) and uPA (P = .011) had independent prognostic value. Combined CD8 negativity and uPA positivity led to a more adverse prognosis in both patients with pT3 tumors and patients with pT4 tumors (P < .001). No difference was observed in the length of survival between patients with pT3 tumors who had CD8 negativity and uPA positivity and patients with pT4 tumors (P = .267). CONCLUSIONS: The multimarker phenotype of the absence of CD8+ TILs, loss of p27, and positive uPA expression was predictive of an adverse prognosis in patients with lymph node-negative, MMR-proficient CRC. The current findings suggested that a subgroup of patients with high-risk, lymph node-negative pT3 tumors should be considered for adjuvant therapy.     

FLEP chemotherapy for alpha-fetoprotein-producing gastric cancer

OBJECTIVE: This study aimed at comparing the efficacy of FLEP chemotherapy in the treatment of stage IV AFP-producing gastric cancer and stage IV non-AFP-producing gastric cancer. METHODS: Between 1989 and 2002, 57 patients with stage IV inoperable gastric cancer were given a combination of chemotherapy with 5-fluorouracil (5-FU), leucovorin (LV), etoposide (VP-16) and cis-diamminedichloroplatinum (CDDP) (designated as FLEP). In the two groups classified histologically according to AFP positivity, the rate of response and conversion to surgery, disease-free and overall survival were compared. The disease-free and overall survival in the two groups was compared by a log-rank test. RESULTS: Patients of the AFP-producing group had a significantly better response rate (70 vs. 31.9%, p = 0.03) and a better conversion rate (40 vs. 12.8%, p = 0.04) than those of the non-AFP-producing group. Patients of the AFP-producing group also had a significantly better disease-free and overall survival (p = 0.02) than those of the non-AFP-producing group. AFP-producing gastric cancer was identified as an independent prognostic factor. CONCLUSION: FLEP chemotherapy was more effective for stage IV AFP-producing gastric cancer than in stage IV non-AFP-producing gastric cancer. Preoperative FLEP chemotherapy improved the prognosis of AFP-producing gastric cancer because of downstaging.     

Lack of any Prognostic Relationship between Adiponectin Receptor (Adipo R1/R2) Expression for Early/ Advanced Stage Gastric Cancer

Introduction: Adiponectin (ApN) is a complement C1q-related protein, mainly secreted from adipose tissue,that signals through ApN receptor1 (Adipo-R1) and ApN receptor 2 (Adipo-R2). Low serum ApN concentrationsare associated with obesity-related malignancies. However, there are very few studies on any prognostic roleof ApN receptors in gastric cancer. Objectives: The aim of this study is to investigate the relationship betweenAdipoR1/R2 expression and early/advanced stage gastric cancer in terms of clinicopathologic characteristicsand survival. Materials and Methods: Eighteen patients with early and 39 with advanced stage gastric cancerwho underwent surgical gastric resection were included in this study. Results: Adipo-R1 expression was low in2 of the 18 patients with early stage gastric cancer (11.1%), while 4 had low Adipo-R2 expression (22.2%). Inthose with advanced stage gastric cancer, 7 of 39 had low Adipo-R1 expression (17.9%) and 16 had low Adipo-R2expression (41%). Adipo-R2 expression was significantly higher (p=0.011) in moderately differentiated tumorswhen compared to well-differentiated tumors. While there was nearly a statistically significant relationshipbetween TNM stage (T, tumor size; N, regional lymph node; M, whether distant metastases exist) and Adipo-R2expression (p=0.054), there was no relationship between Adipo-R1/-R2 expression with tumor stage and survival.Conclusion: Adipo-R1/-R2 expression has no prognostic significance of in early/advanced stage gastric cancer.     

Low level of p27(Kip1) protein expression in gastric adenocarcinoma is associated with disease progression and poor outcome

BACKGROUND AND OBJECTIVES: Low tumor expression of the p27(Kip1) protein, which is involved in cell cycle control and apoptosis, is considered a negative prognostic factor in different types of cancer. The aim of this study was to evaluate the clinical and pathological significance of low p27(Kip1) protein expression in patients who had undergone resection for gastric adenocarcinoma. METHODS: p27(Kip1) protein was studied by immunohistochemistry in formalin-fixed tumor sections from 95 patients who underwent resection for gastric adenocarcinoma between 1991 and 1996. Based on the median value of protein expression, p27(Kip1) protein expression was classified as low or high. RESULTS: Low p27(Kip1) protein expression was significantly associated with tumor de-differentiation, increased penetration through the gastric wall, lymph node metastasis, and advanced tumor stage. In the group of 84 patients who underwent curative surgery, 5-year survival was 74% in cases with high p27(Kip1) protein expression and 38% in those with low p27(Kip1) protein expression (P < 0.001). At multivariate analysis, low p27(Kip1) protein expression was an independent negative prognostic factor for survival (RR = 3.671; P = 0.004). CONCLUSIONS: In gastric adenocarcinoma, low p27(Kip1) protein expression is associated with poorly differentiated and advanced tumors and is a negative prognostic factor of potential clinical value.     

Higher Ki67 Expression is Associates With Unfavorable Prognostic Factors and Shorter Survival in Breast Cancer

Background: The prognostic value of the Ki67 expression level is yet unclear in breast cancer. The aim of thisstudy was to investigate the association between Ki67 expression levels and prognostic factors such as grade, Her2and hormone receptor expression status in breast cancers. Materials and Methods: Clinical and pathologicalfeatures of the patients with breast cancer were retreived from the hospital records. Results: In this study, 163patients with breast cancer were analyzed, with a mean age of 53.4±12.2 years. Median Ki67 positivity was 20%and Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001),estrogen receptor (ER) negativity (p=0.035), Her2 positivity (p=0.001), advanced stage (p<0.001) and lymphnode positivity (p<0.003) . Lower Ki67 levels were significantly associated with longer median relapse-free andoverall survival compared to those of higher Ki67 levels. Conclusions: High Ki67 expression is associated withER negativity, Her2 positivity, higher grade and axillary lymph node involvement in breast cancers. The levelof Ki67 expression is a prognostic factor predicting relapse-free and overall survival in breast cancer patients.     

A modified prognostic score for patients with curatively resected gastric cancer

AIMS AND BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide; the risk of dying depends on several patient and disease characteristics. An existing prognostic score predicts survival in gastric cancer patients undergoing curative resection based on patient age, tumor site, extent of wall invasion and nodal status, categorized as simply as negative or positive. METHODS: Our aim was to modify the original prognostic score by incorporating information on nodal stage according to the latest TNM classification (number of involved nodes), based on a retrospective series of 610 chemotherapy-naive gastric cancer patients recruited to a surgical clinical trial. We then tested the modified score on an independent series of 136 gastric cancer patients. RESULTS: Nodal stage added significant prognostic information to the nodal status classification (P < 0.001), and was therefore included in the modified score. With the latter, we were able to identify three risk groups with overall five-year survival varying from more than 70% to less than 30%. The prognostic performance of the modified score was better than that achieved with the AJCC-UICC TNM staging. CONCLUSIONS: The modified score, based on established prognostic factors, is proposed as a simple tool for prognostic grouping of gastric cancer patients undergoing curative surgery.     

Prognostic indicators for neuroblastoma: Stage,grade, DNA ploidy,MIB-1-proliferation index,p53, HER-2/neu and EGFr–a survival study

Neuroblastoma, a tumor of the sympathetic nervous system, is one of the most common solid malignancies in infants and represents 7% of all cases of childhood cancer outside of the central nervous system. Thirty-five samples of neuroblastoma from 31 patients were obtained from Duke University Medical Center between 1979 and 1991 and studied to determine the relative prognostic value of a number of clinical, histologic, nuclear, and oncogenic features. The features studied were: stage, Shimada classification, DNA ploidy, MIB-1-proliferation index and status for HER-2/neu, p53 and epidermal growth factor receptor (EGFr). Only age (P = .03), HER-2/neu (P = .01), and p53 (P = .02) reached statistical significance as prognostic indicators. The median survival for patients with no HER-2/neu expression was 12 months; median survival for patients with no HER-2/neu expression was 138 months. Similary, the median survival for patients with p53 expression was 12 months; patients with no p53 expression had a median survival was 144 months. The combination of either HER-2/neu or p53 positivity was especially strong as a prognostic indicator (p = .002).     

转录因子Sp1在胃癌中的表达及其与预后的关系

目的 研究转录因子Sp1在胃癌及正常胃黏膜组织中的表达特征,并探讨其表达对胃癌患者预后的影响。方法 用免疫组织化学方法,检测65例胃癌原发灶及40例因胃良性病变行胃部分切除标本中的正常胃黏膜组织Sp1表达情况,观察其表达特性并研究该因子表达与患者长期生存率的关系。结果 所测正常胃黏膜组织Sp1表达阳性率仅为12．5％（5／40）。且均表达于正常胃腺的颈部,在成熟细胞较多的胃腺体底部未见有表达。与之相反,Sp1在胃癌组织中则有较高表达率,为53．8％（35／65）。肿瘤组织中Sp1蛋白呈无表达、弱表达及强表达患者的平均生存期分别为1700d、1560d及1026d,彼此间差异有统计学意义（P=0．036）。Sp1蛋白表达与肿瘤侵袭深度及TNM分期密切相关（P=0．001,P=0．026）,而与淋巴结转移数目及Lauren分型无明显相关（P=0．306,P=0．667）。结论 在正常胃黏膜和胃癌组织中,Sp1蛋白表达具有不同的分布特征。Sp1可作为判断胃癌患者预后的一个独立指标,并可能通过除淋巴结转移以外的其他机制促进肿瘤的侵袭和发展。     

胃癌p16表达的预后意义

目的　探讨基因 p16在胃癌中表达的临床意义特别是与胃癌预后的关系。 方法　用ABC法检测本院 1991年 1月至 1998年 12月间经手术切除的 15 2例胃癌的p16表达状况 ,分析 p16的表达与胃癌分期、组织学类型、分化程度、病灶部位、肿瘤大小及生存率的关系。用Cox比例风险模型评估影响预后的因素。结果　在 15 2例胃癌中 ,p16的表达率为 72 4% ,p16阴性及阳性胃癌在 5年生存率、年龄、性别、肿瘤大小、肿瘤分化程度等方面有显著性差异 ,肿瘤TNM分期及p16的表达状况是影响胃癌预后的独立因素。结论　p16的表达状况可作为判断胃癌预后的指标。     

Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer

The prognostic value of the immunohistochemical expression of epithelial and stromal syndecan-1 was evaluated in 296 patients with gastric carcinoma. Formalin-fixed, paraffin-embedded specimens of gastric adenocarcinomas were stained with mouse monoclonal antibody B-B4 against human syndecan-1. Loss of immunoreactivity (syndecan-1 immunoreactivity correlated with a higher stage of disease (stages II-IV), tumour location in the upper third of the stomach, nodal metastases (N1 or N2), positive stromal syndecan-1 staining, deep tumour penetration (to subserosa or deeper = T2-T4), larger tumour size (> or = 5 cm) and intestinal type of cancer. No correlation between epithelial syndecan-1 immunoreactivity and age, gender, distant metastases, grade of differentiation or Borrmann classification was observed. Positive stromal syndecan-1 immunoreactivity correlated with decreased epithelial syndecan-1 expression, intestinal type of cancer and Borrmann type I. Patients with low epithelial syndecan-1 expression in cancer cells had worse overall survival than patients with strong epithelial syndecan-1 staining (p = 0.0012). Stromal syndecan-1-positive patients had a worse outcome than patients with syndecan-1-negative stroma (p = 0.0193). In Cox multivariate analysis, stromal syndecan-1 immunoreactivity was a prognostic factor independent of TNM stage, surgery for cure and tumour size. Thus, the immunohistochemical expression of syndecan-1 might be a predictor of outcome in patients with gastric adenocarcinoma.     

The prognostic relevance of fascin expression in human gastric carcinoma

OBJECTIVE: Fascin, an actin-bundling protein that is found in membrane ruffles, microspikes, and stress fibers, induces membrane protrusions and increases cell motility in various transformed cells. The expression of fascin in epithelial neoplasms has been described only recently, and its role in gastric cancer is still unknown. METHODS: Paraffin sections of gastric carcinoma from 214 patients were immunohistochemically investigated using monoclonal antifascin antibody. Staining more than 5% of tumor cells was recorded as positive immunoreactivity. RESULTS: Overall, fascin immunoreactivity was detected in 54 out of a total of 214 patients (25%). 26 patients were classified as 1+ (5-25% immunoreactive tumor cells) and 28 were 2+ (>25%). In these patients, 7 tumors showed high (>75%) fascin immunoreactivity. Increased immunoreactivity of fascin was sometimes seen at the edge of the tumor. Fascin immunoreactivity was increased according to the extent of primary tumor (p = 0.026). Fascin expression was correlated with age (p = 0.005), serosal invasion (p = 0.013), positive lymph node metastasis (p = 0.006), histopathological grading (p = 0.019), TNM stage (p = 0.003) and recurrence (p = 0.006); however, it was not correlated with distant metastasis (p = 0.108), Lauren's type (p = 0.205), or R classification (p = 0.056). Among 166 patients with T1, T2, T3 or T4, those with fascin-positive tumors had a significantly poorer prognosis than those with fascin-negative tumors (p = 0.029). Multivariate analysis showed that fascin expression was not an independent poor prognostic factor. CONCLUSION: Our findings suggest that the immunohistochemical detection of fascin could provide useful information as one of the prognostic factors in gastric cancer patients.     

Evaluation of intraoperative intraperitoneal cytology for advanced gastric carcinoma

OBJECTIVE: We evaluated intraperitoneal cytology during surgery as a significant predictor of survival and tried to establish strategies for preventing peritoneal carcinomatosis. METHODS: The study included 236 patients with gastric carcinoma macroscopically invading the serosa who underwent intraperitoneal cytological examination during surgery. In the 215 resected patients, the relationship between cytological positivity for cancer cells and various clinicopathologic features was analyzed. Additionally, postoperative survival was assessed in relation to the positivity of intraoperative cytology. RESULTS: Cancer cells were positive [Cy+] in 78 (33.1%) of 236 patients who underwent cytological examinations. Among 73 patients with peritoneal metastases, 53 patients (72.6%) were Cy+, as were 25 (15.3%) of the 163 patients without peritoneal metastases. Multivariate analysis indicated that peritoneal metastasis (p = 0.0001) and the depth of tumor invasion (p = 0.0069) were significant factors correlated with Cy+. Among patients with curative surgery, the 5-year survival rate of the Cy+ group was 22.2%, which was worse (p = 0.0004) compared with that of the Cy(-) group (60.9%). Among Cy+ patients, the survival rate of the group treated with intraperitoneal administration of mitomycin C (MMC) and OK-432 was better (p = 0.0108) than that of the historical control group. CONCLUSION: These results suggest that intraperitoneal cytological examination can be a significant prognostic factor for gastric carcinoma with serosal invasion. In addition, dissemination of cancer cells in the peritoneum may be controlled by intraperitoneal immunochemotherapy with MMC and OK-432.     

Evaluation of effectiveness of chemotherapy in patients with gastric cancer after curative resection

Background. A prospective randomized study involving gastric cancer patients was undertaken to evaluate combined adjuvant chemotherapy and the prognostic value of biologic markers. Methods. One hundred and eighty-five patients under 75 years of age who underwent a curable resection of pathologic stage II or III gastric cancer were randomly assigned to receive adjuvant chemotherapy containing either: mitomycin C (MMC) plus oral 5-fluorouracil (FU) (MF), epirubicin plus oral FU (EF), or oral FU (F). Tumor tissue collected at surgery was immunohistochemically analyzed for p53 and proliferating cell nuclear antigen, and DNA ploidy was determined. Results. All prognostic factors were equally distributed in each arm. There was no significant difference among the groups in the 5-year overall survival. When the relationship between the biologic markers and prognosis was analyzed, the overall survival of all patients and stage III patients was poorer in those with p53 positivity, but the difference did not achieve significance. For patients with positive nodes, irrespective of the treatment regimen, p53-positivity was significantly associated with poorer prognosis (P = 0.05). In stage III patients, the survival of those with p53-positivity and DNA aneuploidy was significantly worse than that for patients with any other combination (P = 0.02). Conclusion. No survival benefit was observed with the combined chemotherapeutic regimens compared with FU alone. p53 positivity was negatively correlated to survival for node-positive and stage III patients. Received: July 3, 2000 / Accepted: September 21, 2000     

探索淋巴结外侵犯对胃癌患者生存预后的影响（附2 386例报告）

背景与目的：在第8版胃癌TNM分期中,淋巴结外侵犯被列为独立疾病登记变量之一,其阳性患者具有更高的疾病相关病死率和复发率,与不良预后密切相关。探讨淋巴结外侵犯（extracapsular lymph node involvement,EC-LNI）与胃癌临床病理学特征之间的关系,分析其对胃癌患者生存预后的影响。方法：回顾性分析河北医科大学第四医院外三科自2012年1月1日—2015年1月1日行根治性手术治疗的2 386例胃癌患者,分析EC-LNI与临床病理学特征的关系及其对胃癌患者生存预后的影响。结果：2 386例胃癌患者中EC-LNI（+）333例（13.96%）,EC-LNI（-）2 053例（86.04%）。单因素分析结果显示,肿瘤直径、组织学类型、Borrmann分型、浸润深度pT分期、肿瘤pTNM分期、Lauren分型、脉管瘤栓、神经受侵、Ki-67增殖指数、血清肿瘤标志物癌胚抗原（carcinoembryonic antigen,CEA）、糖类抗原（carbohydrate,CA）19-9及CA72-4表达情况均与EC-LNI状态有关（均P<0.05）;多因素分析结果显示,肿瘤直径大小（P=0.010）、组织学类型（P=0.016）、肿瘤浸润深度pT分期（P=0.011）、肿瘤pTNM分期（P=0.003）、Borrmann分型（P=0.032）、脉管瘤栓浸润（P=0.022）均是发生EC-LNI的独立危险因素。2 386例胃癌患者中共有2 273例（95.26%）获得完整随访资料,全组患者5年总生存率（overall survival,OS）为49.32%,5年无病生存率（disease-free survival,DFS）为44.61%。其中EC-LNI（+）者5年OS为27.86%,5年DFS为25.39%,而EC-LNI（-）者5年OS、DFS分别为52.87%、47.79%,两组患者的5年OS、DFS差异均有统计学意义（P均<0.001）。单因素分析显示,EC-LNI数目（P=0.001）与胃癌患者预后有关,同时年龄、病灶部位、肿瘤直径、组织学类型、Borrmann分型、肿瘤浸润深度pT分期、淋巴结转移pN分期、肿瘤pTNM分期、Lauren分型、脉管瘤栓有无、Ki-67阳性比例、术后是否化疗也均与预后相关（均P<0.05）。多因素分析显示,肿瘤组织学类型（P=0.013）、浸润深度pT分期（P=0.020）、淋巴结转移pN分期（P=0.019）、肿瘤pTNM分期（P=0.001）、脉管瘤栓有无（P=0.031）和EC-LNI数目（P=0.001）是影响患者预后的独立危险因素,而术后辅助化疗（P=0.003）是患者预后的保护性因素。结论：EC-LNI与胃癌患者的肿瘤分期及预后密切相关,有无EC-LNI和EC-LNI数目均是影响胃癌患者预后的危险因素。     

Prognostic significance of tenascin-C expression in clear cell renal cell carcinoma

Tenascin-C is an extracellular matrix protein that plays an important role in cell proliferation, migration and tumor invasion in various types of cancer. However, few reports exist on tenascin-C expression in renal cell carcinoma (RCC). This study aimed to assess the prognostic significance of tenascin-C in clear cell RCC. Using immunohistochemistry, 137 formalin-fixed, paraffin-embedded tissue sections obtained from patients with clear cell RCC were examined for tenascin-C expression. Tenascin-C expression was observed in 55 (40.1%) of the 137 clear cell RCC sections. Tumor cells displayed membranous and/or cytoplasmic staining for tenascin-C. Tenascin-C expression was more prominent near the pseudocapsule of the tumor and around the tumor vessels. Tenascin-C expression was significantly associated with a higher stage (P=0.0065) and higher nuclear grade (P=0.0001). However, there was no correlation between the tenascin-C expression and venous involvement. The cancer-specific survival rate in patients with a tenascin-C-positive primary tumor was significantly lower than that in those with a tenascin-C-negative primary tumor in univariate analysis (P=0.0017). However, tenascin-C expression did not exhibit a significant value for cancer-related death in the Cox regression analysis. In patients with stage 1-3 disease, the 5-year metastasis-free rate in patients with the tenascin-C-positive primary tumor was significantly lower than that in those with the tenascin-C-negative primary tumor (67.8 vs. 88.5%, respectively; P=0.0038). The Cox regression analysis showed that tenascin-C expression is a significant predictor of metastasis (P=0.0345). The tenascin-C expression was strongly related to the stage, nuclear grade and 5-year metastasis-free rate. Therefore, tenascin-C expression may be a possible marker for the metastatic potential of clear cell RCC.     

干细胞标志物SOX-2、β-catenin表达与胃癌术后复发转移关系

背景与目的：胃癌术后复发转移严重影响患者生存情况,SOX基因是经典Wnt信号通路的调控因子,其在胃癌术后复发及转移过程中可能发挥重要作用。本研究旨在探讨胃癌术后复发、远处转移患者肿瘤组织中SOX-2、β-catenin表达情况,探讨两者在胃癌术后复发及转移的作用。方法：采用免疫组化方法检测71例经手术切除胃癌患者的肿瘤组织中SOX-2和β-catenin蛋白表达情况,并分析其与临床病理特征和无病生存时间(disease free survival,DFS)的关系。结果：SOX-2在胃癌中的表达与胃癌复发转移、淋巴结浸润及分化程度有关(P=0.011,P=0.036,P=0.034),与患者性别、年龄及T分期无关。β-catenin在胃癌中的表达与胃癌复发转移、淋巴结浸润及T分期有关(P=0.025,P=0.014,P=0.026),与分化程度、患者性别及年龄无关。且二者均呈阳性表达者其术后复发转移率高于任意单阳性者,复发转移率分别为84%(21/25)和66.7%(24/36),二者均阴性表达者其复发转移率为30%(3/10)。生存分析显示SOX-2和β-catenin的表达与患者DFS相关。结论：SOX-2、β-catenin表达可能是胃癌术后复发转移有效的预测因子,两者联合检测有利于预测胃癌患者术后复发转移。