Prognostic evaluation of CD44 expression in correlation with bcl-2 and p53 in colorectal cancer

To investigate the expression of CD44 in colorectal cancer and examine its association with clinicopathological features, bcl-2, p53 and long-term outcome, paraffin-embedded tumour specimens from 61 patients with Dukes stage B (AJCC/UICC stage I) and 39 patients with Dukes stage C (AJCC/UICC stage III) colorectal adenocarcinoma were assessed by immunohistochemistry. The expression of CD44, bcl-2 and p53 were correlated with 5-year follow-up. Low CD44 expression was present in 30%, moderate in 30% and extensive in 40% of cases. It was not related to patient sex and age but was related to tumour differentiation, stage and tumour site. No association was demonstrated between CD44 and bcl-2. However, there was significant evidence of an association between CD44 and p53 in 66 cases in which p53 was previously assessed. There was a trend towards increased survival in patients whose tumours expressed lower levels of CD44 protein. When entered into multivariate analysis model, which also included bcl-2 and p53, CD44 staining emerged as an indicator of poor prognosis in colorectal cancer patients.     

结直肠癌组织RSK4、p53蛋白的表达及临床病理意义

目的:探讨结直肠癌组织中P90核糖体S6激酶4(RSK4)蛋白、p53蛋白的表达及其临床病理意义。方法:选取我院病理科2014年1月~2016年5月既往收集的结直肠癌手术后标本70例及同期结直肠癌癌旁组织30例,采用免疫组化染色检测两组标本中RSK4蛋白、p53蛋白的表达情况,并分析其与结肠癌患者临床病理特征的相关性。结果:结直肠癌组织中RSK4蛋白、p53蛋白的阳性表达率分别为20.00%、55.71%,而癌旁组织中RSK4蛋白、p53蛋白阳性表达率分别为53.33%、10.00%,两组比较差异均具有统计学意义(P0.05)。Ⅰ期+Ⅱ期、高分化和中分化结直肠癌组织RSK4蛋白的阳性表达率显著高于Ⅲ期、低分化结直肠癌(P0.05);Ⅰ期+Ⅱ期、浸润深度(T1、T2)、未发生淋巴结转移的结直肠癌组织中p53蛋白阳性表达率显著的低于Ⅲ期、浸润深度(T3、T4)、发生淋巴结转移的结肠癌组织(P0.05)。结论:结直肠癌组织中RSK4蛋白表达下调、p53蛋白表达上调,二者可能与结直肠癌的发生和发展有关,并可能作为结肠癌诊断和预后评估的参考指标。     

结直肠癌组织中Ezrin和P53的表达及临床病理特征的关系研究

目的:探讨结直肠癌组织中Ezrin和P53的表达及临床病理特征的关系。方法:选取2014年5月至2016年6月我院收治的140例结直肠癌患者,行手术切除结直肠癌组织,经纳入排除标准后,94例癌组织标本纳入本研究并作为研究组,并从中抽取35例手术标本切缘的正常结直肠黏膜组织作为对照组,采用免疫组化测定Ezrin和P53的表达情况,并对两者进行相关性分析。结果:Ezrin、p53蛋白在研究组的表达阳性率分别为52.13%、56.38%,明显高于对照组的0.00%(x~2=25.731、33.496,P0.05)。高、中分化患者Ezrin、p53表达阳性率分别为46.99%、51.81%,明显低于低、未分化患者的90.91%、90.91%(x~2=7.508,P0.05;x~2=4.401,P0.05);有淋巴结转移患者Ezrin、p53表达阳性率分别为77.05%、68.85%,明显高于无淋巴结转移患者的6.06%、33.33%(x~2=43.245,P0.05;x~2=15.846,P0.05);浸润深度T3、T4患者的Ezrin表达阳性率55.81%明显高于浸润深度T1、T2患者的12.50%(x~2=5.503,P0.05);TNM分期Ⅲ、Ⅳ患者Ezrin、p53表达阳性率分别为88.24%、74.51%,明显高于TNM分期Ⅰ、Ⅱ患者的9.30%、34.88%,(x~2=5.522,P0.05;x~2=5.036,P0.05)。49例Ezrin表达阳性患者中,p53表达阳性有11例,而56例Ezrin表达阴性患者中,p53表达阴性14例,Ezrin表达与p53表达无相关性(r=0.209,P0.05)。结论:Ezrin和P53蛋白均与结直肠癌发生和发展存在一定的相关性,有助于结直肠癌预后的判断。     

Aberrant E-cadherin staining patterns in invasive mammary carcinoma

Background

Advances in our understanding of the molecular biology of colorectal cancer have fuelled the search for novel molecular prognostic markers to complement existing staging systems. Markers assessed in combination may perform better than those considered individually. Using high-throughput tissue microarray technology, we describe the prognostic value of combined p53 / Bcl-2 status in colorectal cancer.

Patients and methods

Tumour samples from 462 patients who underwent elective surgery to resect a primary colorectal cancer between 1994 and 2000 (mean follow-up of 75 months) were assembled in tissue microarray format. Clinico-pathological data including tumour grade, stage, vascular invasion status along with disease specific survival data has been collected prospectively. Immunohistochemical analysis of p53 and Bcl-2 expression was performed using antibodies DO-7 (p53) and 124 (Bcl-2), and results correlated with known clinico-pathological variables and outcomes.

Results

Abnormal nuclear p53 accumulation and Bcl-2 overexpression were detected in 221/445 (49.6%) and199/437 (45.5%) tumours respectively, with a significant inverse correlation between the two markers (p = 0.023). On univariate analysis no correlations were found between either marker and standard clinico-pathological variables, however nuclear p53 expression was associated with a significantly reduced survival (p = 0.024). Combined analysis of the two markers indicated that 112/432 (24.2%) cases displayed a p53(-)/Bcl-2(+) phenotype, this occurring more frequently in earlier stage tumours. Kaplan-Meier analysis revealed a significant survival advantage in these p53(-)/Bcl-2(+) tumours compared with the remaining cases (p = 0.0032). On multivariate analysis using the Cox proportional hazards model, neither p53 expression nor Bcl-2 expression alone were of independent prognostic significance, however the combined p53(-)/Bcl-2(+) phenotype was significantly associated with a good prognosis in this series (HR 0.659, 95%CI 0.452–0.959, p = 0.029).

Conclusion

Patient stratification by combined p53 / Bcl-2 phenotype provides stage-independent prognostic information in colorectal cancer. Specifically, that up to a quarter of patients display a good prognosis p53(-)/Bcl-2(+) phenotype. This may indicate a more clinically indolent phenotype and a subset of patients for whom less aggressive adjuvant treatment appropriate.     

Prognostic significance of DNA aneuploidy and p21 ras oncoprotein expression in colorectal cancer and their role in the determination of treatment modalities

The purpose of the present study was to investigate the prognostic significance of DNA ploidy, S-phase fraction and p21 ras oncoprotein expression in patients with colorectal cancer and to correlate these factors with the clinical behavior of the tumors and their response to therapy. Of 79 patients with colorectal cancer 57% (45/79) had early stage disease. Forty-one percent (32/79) had aneuploid tumors while 30% (24/79) of the tumors had a high (>10%) S-phase fraction. p21ras oncoprotein expression was detected in 38% (30/79) of tumors. Patients with aneuploid tumors had a worse prognosis than patients with diploid tumors (p=0.0002). Similarly, patients with high S-phase fraction tumors had a shorter survival than those with low S-phase fraction tumors (p=0.005). No such difference was found between p21 raspositive and p21 ras-negative tumor subgroups. In early stage colorectal cancer, aneuploidy was closely correlated with disease outcome (p=0.029). Early stage patients with diploid tumors who received radiotherapy and chemotherapy had a better prognosis than patients with aneuploid tumors. In conclusion, DNA ploidy is a significant and independent prognostic factor in colorectal cancer. Aneuploidy and genetic alteration of the p21 ras oncoprotein are important in determining the biological aggressiveness of colorectal cancer. Furthermore, DNA ploidy may identify those subgroups of patients with early stage disease who may benefit from more aggressive treatment.     

结直肠癌mP53 和PCNA 表达的相关性及临床意义

目的:探讨结直肠癌中突变型P53基因(mP53)和增殖细胞核抗原(PCNA)表达的相关性及临床意义。方法:应用免疫组化二步法,检测60例结直肠癌组织及20例正常肠粘膜中mP53、PCNA的表达,结合临床病理资料进行统计分析。结果:60例结直肠癌中mP53阳性表达率65.0%,PCNA阳性表达率78.3%,20例正常肠粘膜中mP53、PCNA表达均为阴性(P<0.05)。mP53和PCNA阳性表达率在低分化组、浆膜层浸润组、淋巴结转移组均较高(P均<0.05)。mP53和PCNA表达呈正相关(r=0.58,P<0.05)。结论:mP53和PCNA在结直肠癌中表达均增高,二者与结直肠癌病理学分级、浸润深度和淋巴结转移有关,可作为判断结直肠癌预后的参考指标。     

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI) detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69). Positive LVI was significantly correlated with lymph node metastasis (p < 0.001), tumor size (p < 0.001), histological grading (p = 0.017), tumor depth (p = 0.001), and stage (p < 0.001). Multivariate logistic analysis identified LVI (p = 0.036) as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04) and overall survival (p = 0.032) in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer.     

Ephrin B2 Receptor and Microsatellite Status in Lymph Node-Positive Colon Cancer Survival

BACKGROUND: Ephrin B2 receptor (EphB2) is a target of the canonical wnt pathway implicated in colorectal carcinogenesis, and its down-regulation may be associated with adverse prognosis. We evaluated its prognostic value in resected colon cancer stratified by microsatellite status and other clinicopathologic characteristics. METHODS: We identified all cases of resected stage III colon cancer from 1995 to 2009 managed in the Capital Health district of Nova Scotia. Tissue microarrays were constructed and immunohistochemistry (IHC) for tumor EphB2 staining assigned into quartiles. Microsatellite status was evaluated by IHC for MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2). Microsatellite stable tumors were defined as both MLH1/MSH2 (+/+); tumors staining otherwise were classified with microsatellite instability (MSI-H). Primary and secondary outcomes were disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: We identified 159 cases with sufficient tissue for microarray analysis having a median follow-up of 3.47 years (range, 0.14–14). Median age was 61, 52% were male, 40% had an event, and 29% died. MSI-H was present in 18 (13%). Univariate analysis of EphB2 expression on DFS and OS showed a hazard ratio (HR) of 2.00 (P = .01) and 2.14 (P = .03), respectively. Multivariate analysis of EphB2 expression on DFS and OS showed an HR of 2.24 and 2.23, respectively, with tumor IHC ≤ 50%. CONCLUSIONS: In this cohort, decreased EphB2 expression was an independent prognostic factor for recurrence and death and may have prognostic relevance in tumors with MSI-H. However, this would require prospective validation in a larger study.     

Cytoplasmic Poly（A） Binding Protein 4 Is Highly Expressed in Human Colorectal Cancer and Correlates with Better Prognosis

Cytoplasmic poly(A) binding protein 4(PABPC4) is an RNA-processing protein that plays an important role in the regulation of gene expression.The aim of this study was to investigate the expression pattern and identify the potential clinical significance of PABPC4 in colorectal cancer.Immunohistochemical analysis revealed that 26.7%(27/101 patients) of primary colorectal tumors and 60.5%(23/38 patients) of corresponding adjacent,normal tissues showed high cytoplasmic expression of PABPC4,whereas expression was absent in 98%(43/44 patients) of distant,normal tissues.Using Kaplan-Meier analysis,we observed that the expression of PABPC4 was significantly correlated with disease-free survival and overall survival in patients with stageⅡand stageⅢcolorectal cancer(P = 0.022 and P = 0.020,respectively).PABPC4 expression was positively associated with survival outcome,and may have predictive value in the prognosis of patients with colorectal cancer.Taken together,our findings indicate that PABPC4 may play a role in the pathogenesis of colorectal cancer.     

Ex vivo localization and immunohistochemical detection of sentinel lymph node micrometastasis in patients with colorectal cancer can upgrade tumor staging

ABSTRACT: BACKGROUND: It is not clear if sentinel lymph node (SLN) mapping can improve outcomes in patients with colorectal cancers. The purpose of this study was to determine the prognostic values of ex vivo sentinel lymph node (SLN) mapping and immunohistochemical (IHC) detection of SLN micrometastasis in colorectal cancers. METHODS: Colorectal cancer specimens were obtained during radical resections and the SLN was identified by injecting a 1% isosulfan blue solution submucosally and circumferentially around the tumor within 30 min after surgery. The first node to stain blue was defined as the SLN. SLNs negative by hematoxylin and eosin (HE) staining were further examined for micrometastasis using cytokeratin IHC. RESULTS: A total of 54 patients between 25 and 82 years of age were enrolled, including 32 males and 22 females. More than 70% of patients were T3 or above, about 86% of patients were stage II or III, and approximately 90% of patients had lesions grade II or above. Sentinel lymph nodes were detected in all 54 patients. There were 32 patients in whom no lymph node micrometastasis were detected by HE staining and 22 patients with positive lymph nodes micrometastasis detected by HE staining in non-SLNs. In contrast only 7 SLNs stained positive with HE. Using HE examination as the standard, the sensitivity, non-detection rate, and accuracy rate of SLN micrometastasis detection were 31.8% (7/22), 68.2% (15/22), and 72.2%, respectively. Micrometastasis were identified by ICH in 4 of the 32 patients with HE-negative stained lymph nodes, resulting in an upstaging rate 12.5% (4/32). The 4 patients who were upstaged consisted of 2 stage I patients and 2 stage II patients who were upstaged to stage III. Those without lymph node metastasis by HE staining who were upstaged by IHC detection of micrometastasis had a significantly poorer disease-free survival (p = 0.001) and overall survival (p = 0.004). CONCLUSION: Ex vivo localization and immunohistochemical detection of sentinel lymph node micrometastasis in patients with colorectal cancer can upgrade tumor staging, and may become a factor affecting prognosis and guiding treatment.     

Surgical outcomes for colon and rectal cancer over a decade: results from a consecutive monocentric experience in 902 unselected patients

Background

This study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003.

Methods

A consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed.

Results

Of the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001).

Conclusion

A prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome.     

Penetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by inherited mutations in DNA mismatch-repair genes, most commonly MLH1 or MSH2. The role MSH6 plays in inherited cancer susceptibility is less well defined. The aim of this study was to investigate the penetrance and expressivity of MSH6 mutations in kindreds ascertained through endometrial cancer probands unselected for family history. Detailed pedigrees were constructed for six MSH6 mutation carriers. All reported cancers and precancers were confirmed, and tissues were obtained when available. Tumors were analyzed for microsatellite instability (MSI) and for expression of MSH2, MLH1, and MSH6. MSH6 mutation status was determined for 59 family members. Of these 59 individuals, 19 (32%) had confirmed cancers and precancers. There was an excess of mutation carriers among the 19 affected family members (11 [58%] of 19) compared with those among the 40 unaffecteds (8 [20%] of 40, P=.0065, odds ratio = 5.5, 95% CI = 1.66-18.19). In four of the seven tumors analyzed from mutation carriers other than the probands, MSI and/or MMR protein expression was consistent with the involvement of MSH6. Overall estimated penetrance of the MHS6 mutations was 57.7%. Of the tumors in mutation carriers, 78% were part of the extended HNPCC spectrum. This study demonstrates that MSH6 germline mutations are, indeed, associated with increased cancer risk and that the penetrance of mutations may be higher than appreciated elsewhere. A combination of MSI and immunohistochemistry analyses may be helpful in screening for MSH6 mutation carriers.     

Prognostic Value of E-cadherin-, CD44-, and MSH2-associated Nomograms in Patients With Stage II and III Colorectal Cancer

BACKGROUND: To evaluate the prognostic value of E-cadherin, CD44, and MSH2 expression for colorectal cancer (CRC) and construct nomograms that can predict prognosis. METHODS: We retrospectively analyzed the expression of E-cadherin, CD44, and MSH2 in 223 paraffin-embedded stage II and III CRC specimens using immunohistochemistry in the training cohort. Their prognostic values were assessed using Kaplan–Meier curves and univariate and multivariate COX regression models. Moreover, a number of risk factors were used to form nomograms to evaluate survival, and Harrell's concordance index (C-index) was used to evaluate the predictive accuracy. Further validation of the nomograms was performed in an independent cohort of 115 cases. RESULTS: Low E-cadherin expression and low CD44 expression were significantly associated with diminished overall survival (OS) and disease-free survival (DFS) in stage II and III CRC patients and patients with negative MSH2 expression had better clinical outcomes. Moreover, the multivariate COX analysis identified E-cadherin, CD44 and MSH2 expression as independent prognostic factors for DFS and OS. Using these three markers and three clinicopathological risk variables, two nomograms were constructed and externally validated for predicting OS and DFS (C-index: training cohort, 0.779 (95% CI 0.722–0.835) and 0.771 (0.720–0.822), respectively; validation cohort, 0.773 (0.709–0.837) and 0.670 (0.594–0.747), respectively). CONCLUSION: The expression levels of E-cadherin, CD44 and MSH2 were independent prognostic factors for stage II and III CRC patients. By incorporating clinicopathological features and these biomarkers, we have established two nomograms that could be used to make individualized predictions for OS and DFS.     

RCN2和PEAK1在结直肠癌中的表达与临床病理特征及预后的关系

目的:检测网织钙结合蛋白2(RCN2)和伪足富集的非典型激酶1(PEAK1)蛋白在结直肠癌组织中的表达情况,分析RCN2和PEAK1表达与患者临床病理特征和预后的关系。方法:免疫组织化学法检测90例结直肠癌组织及其癌旁正常组织中RCN2和PEAK1蛋白表达情况,分析结直肠癌组织RCN2和PEAK1表达与患者临床病理特征的关系,Kaplan-Meier生存曲线分析RCN2和PEAK1表达对患者预后的影响,Spearman等级相关检验结直肠癌组织RCN2和PEAK1表达的相关性。结果:RCN2和PEAK1蛋白在结直肠癌组织中的阳性表达率均明显高于癌旁正常组织(P0.05)。结直肠癌组织RCN2表达与肿瘤直径、浸润深度和TNM分期均有关(P0.05),PEAK1表达与肿瘤浸润深度、淋巴结转移和TNM分期均有关(P0.05)。Log Rank检验结果显示,RCN2阳性表达组和PEAK1阳性表达组患者的术后5年总生存率均分别低于RCN2阴性表达组和PEAK1阴性表达组患者(P0.05)。结直肠癌组织RCN2和PEAK1表达呈正相关性(r=0.586,P=0.000)。结论:RCN2和PEAK1蛋白在结直肠癌组织中呈高表达,且均与肿瘤恶性进展和不良预后关系密切。RCN2和PEAK1可作为结直肠癌治疗靶标的候选分子。     

Clinical Significance of Frizzled Homolog 3 Protein in Colorectal Cancer Patients

Frizzled homolog 3 receptor was up-regulated in several gastrointestinal cancers such as esophageal and gastric cancers. Moreover, frizzled homolog 3 has recently reported to be expressed in colorectal adenoma specimens. In the present study, we investigated the clinical significance of frizzled homolog 3 protein in colorectal cancer patients. Using immunocytochemical staining, frizzled homolog 3 expression was examined in 186 colorectal cancer specimens, 79 colorectal adenoma specimens, 133 colorectal polyp specimens, 127 colorectal cancer specimens with lymph node and/or distant metastasis, 310 specimens of various non-colorectal cancer metastatic carcinomas and 40 specimens with simultaneous occurrence of colorectal cancer, colorectal adenoma and colorectal polyp. Statistical analysis was used to correlate frizzled homolog 3 protein expression to the clinicohistopathological factors, recurrence/metastasis and survival after follow-up for 42 months in colorectal cancer patients. Frizzled homolog 3 protein was expressed in 100% colorectal cancer specimens, 89% colorectal adenoma specimens, 75% colorectal polyp specimens and 69% normal colorectal epithelial tissues. Moreover, frizzled homolog 3 immunocytochemical scores were highly correlated with colorectal cancer progression. Furthermore, frizzled homolog 3 was expressed in a comparatively lower percentage of metastatic hepatocellular carcinoma and metastatic renal clear cell carcinoma with focal and very weak staining than other metastatic tumor types. On the other hand, the frizzled homolog 3 immunocytochemical scores of colorectal adenomas with synchronous colorectal carcinomas were significantly higher than those of pure colorectal adenomas. Statistical analysis showed that frizzled homolog 3 immunocytochemical scores were associated with Dukes stage and lymph node status. Finally, stratified groups of colorectal cancer patients had significant differences in their recurrence/metastasis and survival. In conclusion, the present large-scale study has clearly showed that frizzled homolog 3 protein can generate clinically important information for colorectal cancer patients.     

Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer

BACKGROUND: Prognostic factors from clinical, laboratory and pathological data of patients with colorectal cancer are essential to identify high-risk groups to whom beneficial adjuvant therapy could be given. Endothelin-1, a growth factor, has been associated with the development and spread of solid tumours. This prospective study was performed to determine whether preoperative plasma big ET-1 levels might be useful as a prognostic indicator in patients with colorectal carcinoma. METHOD: Sixty-five consecutive patients with colorectal cancer confirmed by biopsy were included prospectively into this study over a 12-month period. Plasma samples from a peripheral vein were obtained prior to surgery. Univariate analysis of survival using age (< or > 70 years), sex, Dukes' stage (A&B versus C), tumour size (< or > 50 mm), vascular invasion and plasma big ET-1 levels was performed and significant factors were then analysed with the Cox regression model. RESULTS: Three variables, age, Dukes' tumour stage and plasma big ET-1 levels, were found to have prognostic significance (p<0.05). Factors associated with a poorer prognosis were age >70 years (p=0.02), Dukes' C tumours (p=0.04) and plasma big ET-1 levels >4.2 pg/mL (p=0.02). The Cox regression model identified the same three variables as having independent prognostic value for overall survival. CONCLUSION: Preoperative plasma big ET-1 levels may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 levels may be useful in the selection of high-risk lymph node-negative patients with colorectal cancer for adjuvant therapy.     

大肠癌组织中TS和COX-2的表达及其与患者无病生存期的关系

目的:探讨大肠癌患者癌组织中环氧化酶-2(COX-2)、胸苷酸合成酶(TS)的表达及其与患者无病生存期的关系。方法:筛选我院收治的大肠癌根治术患者,选择无病生存期大于48个月者30例和无病生存期小于48个月者29例。采用免疫组化法检测大肠癌组织中COX-2和TS的表达,并分析其与患者无病生存期的关系。结果:49例结直肠癌患者中,TS的阳性表达率为91.84%,COX-2的阳性表达率为77.55%。不同无病生存期的大肠癌患者TS的表达水平比较无统计学差异(P=0.646)。COX-2在无病生存期48个月的患者癌组织中表达水平明显低于无病生存期48个月的患者,差异有统计学意义(P=0.033)。结论:COX-2与大肠癌患者的无病生存期显著相关,可能成为预测大肠癌预后的参考指标。     

Preoperative plasma soluble urokinase plasminogen activator receptor as a prognostic marker in rectal cancer patients. An EORTC-Receptor and Biomarker Group collaboration

BACKGROUND AND AIMS: Since approximately 30% of patients with Dukes' stage B colorectal cancer will experience disease recurrence within five years of primary treatment, current staging of patients with early colorectal cancer apparently fails to adequately predict patient outcome. It has previously been shown that the preoperative plasma concentration of soluble urokinase plasminogen activator receptor (suPAR) is associated with the survival of patients with early colorectal cancer. In this study we sought to confirm the independent prognostic value of suPAR in rectal cancer. METHODS: suPAR was retrospectively determined by two different versions of a suPAR ELISA in preoperatively collected plasma samples from a Swedish (n = 354) and a Danish (n = 255) cohort of rectal cancer patients. RESULTS: In both cohorts the suPAR concentration was significantly higher in Dukes' stage D patients than in Dukes' stage A-C patients (p < 0.0001). Among Dukes' stage A-C patients, no differences in median suPAR values were seen. In univariate analysis, continuous suPAR was found to be associated with survival (p < 0.0001 in both cohorts). Of particular interest was that similar results were obtained for Dukes' stage A and B patients when analyzed separately. In multivariate analysis, continuous suPAR was found in both cohorts to be independent of Dukes' stage. CONCLUSIONS: This study confirms that the preoperative concentration of plasma suPAR contains independent prognostic information on patients with rectal cancer. This result was independent of the two different versions of an in-house suPAR ELISA used to perform the analyses. The next step in the evaluation of suPAR as a prognostic parameter in rectal cancer will be to launch an appropriately dimensioned prospective study where the benefit of applying preoperative plasma suPAR measurement to clinical decision-making regarding adjuvant therapy is assessed.     

Nuclear and cytoplasmic expression of ErbB-4 in prostate cancer

PURPOSE: To evaluate cytoplasmic and nuclear ErbB-4 expression in prostate cancer specimens and its association with outcome. BASIC PROCEDURES: Specimens of 50 prostate cancer patients were investigated for ErbB-4 overexpression using Immunohistochemistry staining. Cytoplasmic and nuclear staining was graded as 0-3 according to its intensity. The prognostic parameters were tumor stage, PSA level, Gleason score, probability of positive lymph nodes (Partin's tables and Roach equation), and 5-year disease free survival (Kattan nomogram). MAIN FINDINGS: Overexpression of ErbB-4 (> or = 1) was detected in 30 (60%) patients and overexpression using cytoplasmic and nuclear staining was > or = 2 in 19 (38%) and 17 (34%) patients, respectively. In only one third of the specimens was there any similarity between the 2 types of staining. Advanced tumor stage, high pretreatment PSA levels and high Gleason scores were evenly distributed among the patients with low (< or = 1) and intermediate/high (> or = 2) ErbB-4 expression. The probability of lymph node involvement and 5-year disease free survival were similar in both types of staining. PRINCIPAL CONCLUSIONS: ErbB-4 was overexpressed (cytoplasmic and nuclear staining) in approximately one third of prostate cancer patients. The rate of similarity between the 2 staining types was only 33%: overexpression was evenly distributed among intermediate/high and low risk prostate cancer patients with both staining methods.