Serum HCG beta,CA 72-4 and CEA are independent prognostic factors in colorectal cancer

In colorectal cancer, stage is considered to be the strongest prognostic factor, but also serum tumour markers have been reported to be of prognostic value. The aim of our study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4 and free beta subunit of human chorionic gonadotropin (hCG beta) in colorectal cancer. Preoperative serum samples were obtained from 204 colorectal cancer patients, including 31 patients with Dukes' A, 70 with Dukes' B, 49 with Dukes' C and 54 with Dukes' D cancer. The serum levels of CEA, CA 19-9, CA 242 and CA 72-4 were measured with commercial kits with cut-off values of 5 microg/L for CEA, 37 kU/L for CA 19-9, 20 kU/L for CA 242 and 6 kU/L for CA 72-4. The serum hCG beta was quantitated by an immunofluorometric assay (IFMA) with 2 pmol/L as a cut-off value. Survival analyses were performed with Kaplan-Meier life tables, log-rank test and Cox proportional hazards model. The sensitivity was 44% for CEA, 26% for CA 19-9, 36% for CA 242, 27% for CA 72-4 and 16% for hCG beta. The overall 5-year survival was 55%, and in Dukes' A, B, C and D cancers the survival was 89%, 77%, 52% and 3%, respectively. Elevated serum values of all markers correlated with worse survival (p < 0.001). In Cox multivariate analysis, the strongest prognostic factor was Dukes' stage (p < 0.001), followed by tumour location (p = 0.002) and preoperative serum markers hCG beta (p = 0.002), CA 72-4 (p = 0.003) and CEA (p = 0.005). In conclusion, elevated CEA, CA 19-9, CA 242, CA 72-4 and hCG beta relate to poor outcome in colorectal cancer. In multivariate analysis, independent prognostic significance was observed with hCG beta, CA 72-4 and CEA.     

Preoperative carcinoembryonic antigen level as an independent prognostic factor in colorectal cancer: Taiwan experience

BACKGROUND: Preoperative carcinoembryonic antigen (CEA) level is considered as a factor predictive of survival in colorectal cancer patients. Patients with normal (<5 ng/ml) or lower preoperative CEA levels were reported to have significantly longer survival. This study was carried out in an effort to evaluate the prognostic significance of preoperative CEA levels of patients with colorectal cancer in Taiwan. METHODS: Between 1990 and 1994, 218 patients with histologically confirmed colorectal cancers were evaluated retrospectively at the Veterans General Hospital-Taipei. All the patients had undergone potentially curative surgery. Patients with metastatic diseases were not included. 5-Fluorouracil-based adjuvant chemotherapy was administered if the patients had Dukes' C disease. Reference to the Dukes' classification was according to the classical criteria described in 1932 for carcinoma of the rectum and adapted for use in colonic tumors. Data on gender, age, degree of tumor differentiation, location of the tumor, tumor size, lymph node metastasis, penetration of the bowel wall and preoperative CEA levels were analyzed to determine their association with survival. Blood samples for CEA measurement were taken a few days before operation and were analyzed using the radioimmunoassay method. Multivariate analysis by Cox's proportional hazards regression model was performed to determine the most important predictors of survival among all of the possible variables. RESULTS: By univariate analysis, the size of the tumor (p = 0.012), lymph node metastases (p = 0.007), penetration of the bowel wall (p < 0.001) and preoperative CEA levels (p < 0.001) were found to be significant prognostic factors, while gender, age, degree of tumor differentiation and location of the tumor were not significant. By multivariate Cox analysis, lymph node metastases (p = 0.003), penetration of the bowel wall (p = 0.0001) and preoperative CEA levels (p = 0.0001) were found to be independent prognostic factors in colorectal cancer patients. CONCLUSIONS: The data from our study indicate that in addition to lymph node metastases and penetration of the bowel wall, the preoperative CEA levels are also an independent prognostic factor in non-metastatic colorectal cancer patients after curative surgery. This could serve as an appropriate modification to the initial Dukes' scheme in colorectal cancer.     

Thymidylate synthase expression: an independent prognostic factor for local recurrence, distant metastasis, disease-free and overall survival in rectal cancer.

Several studies have suggested that the intratumoral level of thymidylate synthase (TS) in colorectal tumors correlates with survival. We have studied the correlation between TS expression in primary rectal cancer and locoregional recurrence, distant metastases, and survival. TS enzyme levels were evaluated immunohistochemically using the specific monoclonal antibody TS 106 in paraffin-embedded tumors from 243 patients who had undergone primary surgery for rectal cancer during the years 1980-1993. All patients were included in prospective randomized trials aimed at determining the clinical value of a short preoperative course of local radiation therapy (five doses of 5 Gy each). With a median follow-up of 94 months (range, 43-202 months), it was observed by multivariate analysis that Dukes' stage and TS expression were independent prognostic markers of locoregional recurrence (P < 0.001 and P = 0.038, respectively) distant metastasis (P < 0.001 and P = 0.011, respectively) disease-free survival (P < 0.001 and 0.014, respectively), and overall survival (P < 0.001 and 0.020, respectively). By multivariate analysis, preoperative irradiation therapy showed a borderline improvement in locoregional recurrence (P = 0.051). No other factors, such as age, sex, differentiation of the tumor, or p53 expression, were noted to be independent prognostic factors for clinical outcome in these patients. We concluded that the intratumoral expression of TS in primary rectal cancer is an independent prognostic factor for locoregional recurrence, distant metastases, disease-free survival, and overall survival. Patients with low intratumoral TS expression had a significantly better outcome than those with high TS expression.     

Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy

PURPOSE: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients. METHODS AND MATERIALS: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT. RESULTS: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p = 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes' stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01). CONCLUSION: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT.     

Prognostic importance of the soluble plasminogen activator receptor, suPAR, in plasma from rectal cancer patients

Colorectal cancer is one of the most common tumour types with approximately one third of the tumours located within the rectum. Rectal cancer differs somewhat from colon cancer, e.g. regarding the method of operation and the use of preoperative radiotherapy due to a tendency for local tumour recurrence. Proteolytic enzymes have been identified as key molecules in tumour invasion and metastasis, and factors within the urokinase-plasminogen activation (uPA) system have been associated with prognosis in several tumour types, including colorectal cancer. Recently, methods have been developed to analyse the soluble fraction of the plasminogen activator receptor (suPAR) in blood samples. An association between elevated suPAR levels and poor prognosis has recently been demonstrated in colorectal cancer. We have measured suPAR levels in pretreatment plasma samples from 173 rectal cancer patients in order to confirm its prognostic strength in this clinical entity. suPAR levels were determined in ethylenediamine tetraacetic acid (EDTA) plasma by a kinetic enzyme-linked immunosorbent assay (ELISA) and analysed with respect to sex, age, Dukes' stage, tumour differentiation grade and survival. In a univariate analysis, continuous suPAR plasma levels were associated with survival (P<0.001) with shorter survival among patients with high suPAR values. Patients with suPAR values within the upper quartile had significantly shorter survival (hazard ratio (HR) 2.2, 95% confidence interval (CI) 1.3-43.7, P=0.002). In a multivariate Cox analysis, increasing suPAR values predicted shorter survival independent from Dukes' stage and tumour differentiation grade with an adjusted HR of 2.2 per ng/ml suPAR (95% CI 1.2-4.0, P=0.01). This study thus confirms that measurement of suPAR in preoperative plasma samples gives independent prognostic information in rectal cancer patients, higher values being associated with shorter survival.     

KAI1/CD82 expression as a prognosic factor in sporadic colorectal cancer

BACKGROUND: Since its identification as a suppressor gene for prostate cancer metastasis, down-regulation of KAI1/CD82 in a variety of malignancies has been reported. MATERIALS AND METHODS: Using immunohistochemistry, we examined KAI1/CD82 expression in surgical specimens obtained from 70 patients with advanced colorectal cancer and its correlation with clinicopathological factors, to clarify their prognostic significance. RESULTS: KAI1/CD82 expression was positive in 55% of the 70 colorectal cancers. There were statistically significant correlations between KAI1/CD82 expression and Dukes' stage, venous invasion, lymph node metastasis, tumor differentiation and liver metastasis. The significant correlation between KAI1/CD82 expression and outcome among patients with Dukes' C cancer (p=0.024) is particularly noteworthy. On multivariate analysis, KAI1/CD82 expression and Dukes' stage were identified as significant and independent prognostic factors (p=0.006 and 0.045, respectively). CONCLUSION: KAI1/CD82 expression closely correlates with clinicopathological factors for colorectal cancers. KAI1/CD82 expression appears to be a useful prognostic marker.     

Prognostic significance of nm23 gene product expression in patients with colorectal carcinoma treated with radical intent

Reports of the relationship between the putative metastasis suppressor NM23 and metastasis and/or survival in colorectal cancer patients are conflicting. This study aimed to investigate whether nm23 immunostaining is correlated with established prognostic variables (Dukes' stage, degree of tumour differentiation, T stage and nodal involvement) in colorectal carcinomas for the patients treated with radical intent using Kruskal chi(2) analysis. The rates of survival at five years were estimated with the use of the Kaplan-Meier product-limit method with 95% confidence intervals derived by Greenwood's formula and the curves were compared with the use of the log-rank test. Cox proportional-hazard regression model was used to identify multivariate predictors and the corresponding outcome. The staining was performed on 112 paraffin-embedded surgical specimens collected between 1989-1992 using a monoclonal anti-nm23 antibody. Follow-up of patients was until time of death or for at least 5 years. There was not a significant correlation between tumour staging, degree of tumour differentiation, nodal involvement and nm23 status. Furthermore, there was no significant association with overall 5-year survival, disease recurrence, tumour site, age or sex. Although nm23 may be involved in suppressing tumour metastasis, nm23 immunohistochemistry has no prognostic value in colorectal cancer. For these reasons nm23 does not contribute further to the prognostic information provided by established prognostic variables.     

Survivin和Livin在Dukes'B期结直肠癌中的表达及其临床意义

背景与目的：Survivin和Livin是新发现的凋亡抑制蛋白（inhibitors of apoptosis proteins,IAPs）家族成员,特异性表达于肿瘤细胞和胚胎细胞,在正常细胞中较少表达,其表达与部分肿瘤预后不良相关.本研究检测Survivin及Livin在Dukes＇B期结直肠癌组织中的表达并分析其临床意义.方法：收集81例根治性手术切除后的Dukes＇B期结直肠癌组织,利用免疫组化SP法检测Survivin及Livin的表达并分析两种蛋白与临床特征的关系及对患者生存的影响.结果：Survivin和Livin在Dukes＇B期结直肠癌组织中的阳性率分别为58.0%和45.7%,明显高于正常对照组的16.7%和8.3%（P值均＜0.05）;两者表达不具有相关性（P＞0.05）;Survivin及Livin在结直肠癌组织中的表达与性别、肿瘤部位、肿瘤大小、T分期、大体类型、组织分化程度均无显著性相关（P值均＞0.05）;≥50岁患者Survivin的阳性率高于＜50岁患者（70.6%vs.36.7%,P＜0.05）;Survivin和Livin的表达均与肿瘤复发和/或转移（P=0.02,P=0.001）、总生存不佳有关（P=0.039,P=0.001）;Cox多因素分析显示T4及Livin阳性为Dukes＇B期结直肠癌独立不良预后因素（P=0.002,P=0.047）.结论：Survivin及Livin高表达于Dukes＇B期结直肠癌组织中,Livin与根治性手术后的复发转移和患者预后关系密切.     

Serum YKL-40 and colorectal cancer

YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three hundred and forty patients died. Sixteen per cent of the patients with Dukes' A, 26% with Dukes' B, 19% with Dukes' C and 39% with Dukes' D had high serum YKL-40 levels (adjusted for age). Analysis of serum YKL-40 as a continuous variable showed an association between increased serum YKL-40 and short survival (P < 0.0001). Patients with high preoperative serum YKL-40 concentration had significantly shorter survival than patients with normal YKL-40 (HR = 1.7; 95% CI: 1.3-2.1, P < 0.0001). Multivariate Cox analysis including serum YKL-40, serum CEA, Dukes' stage, age and gender showed that high YKL-40 was an independent prognostic variable for short survival (HR = 1.4; 95% CI: 1.1-1.8, P = 0.007). These results suggest that YKL-40 may play an important role in tumour invasion.     

The preoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of colorectal cancer

A study of preoperative carcinoembryonic antigen (CEA) levels was conducted in 319 patients with surgically treated colorectal cancer, 272 of whom had disease resectable with curative intent. Only three patients could not be completely followed. All of the remaining 316 patients have been followed for a minimum of 5 years or until death. From the standpoint of diagnosis, the CEA test was more frequently positive (greater than 5 ng/ml) in patients with advanced stage disease, with larger primary tumors, and with more differentiated histopathologic characteristics. It was grossly insensitive in diagnosis of resectable cancer (26%) and was only reasonably reliable (72%) in patients with unresectable and metastatic disease. In relationship to surgical pathology of colorectal cancer, CEA levels were significantly correlated with stage of disease and with size of the primary tumor in Dukes' B lesions, but not with extent of nodal metastasis in Dukes' C lesions. In advanced stage lesions, CEA was inversely correlated with degree of anaplasia. In the overall patient group, and also among resectable patients, the preoperative CEA level was strongly associated with survival after adjustment for the effects of a number of other prognostic factors. Within stages of resectable disease, however, CEA was not significantly associated with survival among patients with Dukes' A and B lesions or Dukes' C lesions with one to three nodes involved. CEA was found to be a significant and independent prognostic determinant only in patients with Dukes' C lesions who had four or more metastatically involved lymph nodes. Under these circumstances, a preoperative CEA level could perhaps be of some value for stratification of Dukes' C patients in randomized colorectal cancer surgical adjuvant trials. The value of this test as a prognostic guide in clinical practice, however, would seem to be limited because of a lack of sensitivity in identifying individual poor prognosis patients.     

Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.

Evidence as to the value of preoperative carcinoembryonic antigen (CEA) in guiding treatment for patients with colorectal cancer is conflicting. The aim of this prospective study was to investigate the value of preoperative CEA in predicting tumour factors of proven prognostic value and long-term survival in patients undergoing surgery for colorectal cancer. Preoperative serum CEA, tumour ploidy, stage and grade were ascertained in 277 patients undergoing colorectal cancer surgery. This cohort of patients were followed up for a minimum of 5 years, or until death, in a dedicated colorectal clinic. Patients with an elevated CEA had a 5 year survival of 39%. This increased to 57% if the CEA was normal (P=0.001). The proportion of patients with a raised CEA increased with a more advanced tumour stage (P < 0.000001) and a poorly differentiated tumour grade (P < 0.005). Once stage had been controlled for, CEA was not a predictor of survival. No relationship between tumour ploidy and CEA was found. In conclusion, a raised preoperative serum CEA is likely to be associated with advanced tumour stage and poor long-term survival, compared with patients with a normal value.     

免疫组化检测Survivin和Livin表达可预测Dukes'''' B期结直肠癌术后的复发和生存

Objective： To detect the expressions of Survivin and Livin in Dukes＇ B colorectal cancer tissues and analyze the prognosis after curative resection. Methods： The expressions of Survivin and Livin were evaluated immunohistochemically in Dukes＇ B colorectal cancer specimens from 81 patients after curative resection of the tumor. Their correlations to clinical characters and survival were also explored. Results： The positive rates of Survivin and Livin in colorectal cancer tissues were significantly higher than those in normal colorectal tissues （58.0% vs. 16.7% and 45.7% vs. 8.3% respectively, P 〈 0.05）. The expressions of Survivin and Livin were not related to gender, tumor site, primary size, T stage, pathologic category, and degree of differentiation （P 〉 0.05）, and no relationship was found between the expressions of Survivin and Livin （P 〉 0.05）. The expression rate of Survivin in patients older than 50 years was higher than that in patients younger than 50 years （70.6% vs. 36.7%, P 〈 0.05）. Both Survivin and Livin were related to recurrence and/or metastasis （P = 0.02 and P = 0.001, respectively）, and shorter survival （P = 0.039 and P = 0.001, respectively）. Cox multivariate analysis showed T4 and positive Livin expression were independent prognostic factors （P = 0.002 and P = 0.047, respectively）. Conclusion： Survivin and Livin are over-expressed in Dukes＇ B colorectal cancer tissues and are positively related to recurrence and/or metastasis and poor prognosis after curative resection of the tumor.     

Selection criteria for high risk and low risk groups of recurrence and metastasis in patients with primary colorectal cancer

Among 371 patients with primary colorectal cancer, 54 patients suffered from recurrence/metastasis (recurrence group) and 317 survived without recurrence for at least 5 years (non-recurrence group). The clinicopathological characteristics of the 2 groups were compared and occult neoplastic cells (ONCs) in the lymph node sinuses were detected by cytokeratin immunohistochemistry. There were significant differences of the following factors: venous invasion (v-) vs. (v+) for Dukes' A patients (p=0.0315); harvested lymph nodes (LN) or=15 for Dukes' B patients (p=0.0388); (v-) vs. (v+) (p=0.0059), lymphatic invasion (ly-) vs. (ly+) (p=0.0435) for Dukes' A and B patients combined; D>n vs. D=n (p=0.0033), depth of tumor invasion or=se/a2 (p=0.0329) for Dukes' C patients. When the detection of >or=3 ONCs was defined as positive, the sensitivity, specificity, PPV, and NPV were respectively 77%, 100%, 100% and 71% in Dukes' B patients, as well as 75%, 72%, 73% and 74% in Dukes' C patients. The high-risk groups for recurrence/metastasis were identified by the following criteria: (v+) and (ly+), or=se/a2, and ONCs (+) of those with >or=2 factors for Dukes' C patients (selection rate; approximately 21.2-37.5%). These factors seem to be appropriate for separating patients into high-risk and low-risk groups of colorectal cancer recurrence/metastasis.     

Growth potential of human colorectal carcinomas in nude mice: association with the preoperative serum concentration of carcinoembryonic antigen in patients

A preoperative serum carcinoembryonic antigen (CEA) concentration greater than 5 ng/ml portends a poor prognosis for patients with colorectal carcinoma. The purpose of this study was to determine if the tumorigenicity of colorectal carcinomas in nude mice was associated with the preoperative serum CEA concentration. Neoplasms from 53 patients were either implanted as fragments or dissociated with collagenase and DNase, and 3 x 10(6) viable cells were injected into the flanks of BALB/c nude mice. The growth potential of tumors resected from patients with CEA levels exceeding 5 ng/ml was greater than that of tumors from patients with normal serum CEA: 26 of 33 carcinomas from patients with CEA greater than or equal to 5 ng/ml were tumorigenic in nude mice, whereas only 8 of 22 neoplasms from patients with normal serum CEA were tumorigenic in nude mice (P less than 0.001). Primary colorectal cancers, not metastases, were the basis for the association between tumorigenicity and preoperative CEA. Tumorigenicity was also associated with stage of disease, since Dukes' D primary tumors and metastases were more tumorigenic than Dukes' A to C primary tumors. Growth in nude mice was not associated with other prognostic factors such as tumor site, mucin production, local invasion, or stage of histological differentiation. The tumorigenic capability of human colorectal carcinomas may be associated with the preoperative serum CEA concentration and may reflect an increased potential to develop clinical metastases.     

结直肠癌根治术后复发转移的多因素分析

复发转移是结直肠癌术后非常重要的预后因素,而复发转移的相关因素是大肠癌根治术后个体化随访和辅助治疗的依据。本文旨在探讨结直肠癌根治术后复发转移的相关临床病理因素。     

The prognostic value of argyrophil nucleolar organiser regions (AgNORs) in colorectal cancer.

Argyrophil nucleolar organiser regions (AgNORs) are increased in a variety of malignant cells compared with normal cells, and a recent study has claimed that AgNORs have prognostic value in colorectal cancer. We have studied the AgNOR counts in tumours from 95 colonic resections performed in 94 patients in whom a minimum 5 year follow-up was available. In 71 pathological specimens adjacent normal mucosa was also examined. There was a significant difference between AgNORs per cell in normal mucosa (median 1.46, range 1.10-1.80) compared with tumour cells (median 1.92, range 1.42-2.95, P less than 0.001). There were no significant differences in average AgNORs per cell between tumours in each Dukes' stage or category of differentiation. The average AgNORs per cell in tumours of patients surviving disease-free for 5 years was the same as that in tumours of patients dying of colonic cancer recurrence. We conclude that AgNORs have no prognostic value in colorectal cancer and are not correlated with Dukes' staging or differentiation of the tumour.     

Correlation between occult neoplastic cells in the lymph node sinuses and recurrence in patients with curatively resected Dukes' B colorectal cancer

This study investigated whether it is possible to detect patients who have a high risk of metastasis and recurrence after resection of stage II Dukes' B primary colorectal cancer. Among 434 patients who underwent curative resection of primary colorectal cancer, 167 (38.5%) had Dukes' B cancer. Among them, 19 patients (11.4%) suffered from postoperative metastasis or recurrence. In 17 patients with recurrence who could be followed-up completely (recurrence group) and 17 other patients who survived for at least 5 years without recurrence (non-recurrence group), immunohistochemical staining of resected lymph nodes for cytokeratin (AE1/AE3 and CAM 5.2) was performed. AE1/AE3 was positive in 76.5% and 47.1% of the patients from the recurrence and non-recurrence groups, respectively, while CAM 5.2 was positive in 52.9% and 17.6%, respectively. There were no significant differences of either AE1/AE3 or CAM 5.2 positivity between the groups. However, the occult neoplastic cell count (mean +/- SD) floating in the lymph node sinuses was significantly higher in patients from the recurrence group who were positive for AE1/AE3 or CAM 5.2 than in patients from the non-recurrence group (6.12+/-6.00 vs. 0.59+/-0.71; p=0.0019 and 3.94+/-5.06 vs. 0.29+/-0.69; p=0.0098, respectively). These results suggest that patients with Dukes' B primary colorectal cancer who have a higher risk of recurrence can be selected by immunostaining of resected lymph nodes for cytokeratin.     

Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis.

BACKGROUND: The proteolytic enzyme plasmin, which is generated from the precursor plasminogen by the action of urokinase plasminogen activator, is thought to play a role in tumor cell invasion and metastasis. Urokinase plasminogen activator receptor (uPAR) is functionally involved in the cell surface activation (i.e., cleavage) of plasminogen. Increased tumor tissue levels of uPAR are associated with poor prognosis in several types of cancer. This retrospective study was undertaken to test the relationship between preoperative plasma levels of soluble uPAR (suPAR) and survival in patients with colorectal cancer. METHODS: suPAR levels in preoperative plasma from 591 patients with colorectal cancer were determined by use of a kinetic enzyme-linked immunosorbent assay and analyzed with respect to associations with postoperative survival, Dukes' stage, age, and serum carcinoembryonic antigen level. Plasma suPAR measurements were log transformed for survival analysis, which employed the Kaplan-Meier method and the Cox proportional hazards model. All P values reported are two-sided. RESULTS: Univariate analysis, using the log-transformed suPAR concentrations, demonstrated that there was an increasing risk of mortality with increasing plasma suPAR level (P<.0001). An arbitrary cut point, the median for all patients (1.37 ng/mL), divided patients with Dukes' stage B, C, or D disease into statistically different prognostic groups. In multivariate Cox analysis including Dukes' stage, age, and carcinoembryonic antigen level, the suPAR concentration independently predicted survival (P<.0001). CONCLUSIONS: The preoperative plasma suPAR level independently predicted survival of patients with colorectal cancer. Further studies of plasma suPAR in patients with cancer are needed to evaluate the utility of plasma suPAR measurements and cut points in identifying high-risk patients among those with early stage disease.     

p53 mutation found to be a significant prognostic indicator in distal colorectal cancer

There has been few reports describing that the prognostic significance of p53 alteration in colorectal tumors depended on the site of origin. Therefore, in this study, we examined whether there is a valid association between the p53 alterations and the prognosis of colorectal cancer patients, especially distal colorectal cancer cases. Tumor samples were collected from 110 patients resected for colorectal cancer between 1989 and 1997. The entire coding region of the p53 gene was analyzed by automated direct sequencing. In addition, the DO-7 monoclonal antibody was used in the immunohistochemical (IHC) assessments. By the Cox univariate analyses in all tumors, Dukes' stage, lymph node metastasis, liver metastasis, p53 mutation and p53 protein overexpression were significant predictors of survival. The cases without p53 mutation showed significantly improved prognosis compared to the cases with p53 mutation (p = 0.0085). In distal tumors, Dukes' stage, liver metastasis, p53 mutation and p53 protein overexpression were significant predictors of survival. Multivariate analysis of all tumors, p53 mutation and liver metastasis were independent indicators of poor survival (p = 0.0223 for p53 mutation, p = 0.0254 for liver metastasis). Also in distal tumors, p53 mutation was an independent indicator (p = 0.0011). Furthermore, the relative risk associated with p53 mutation in distal tumors was much higher than that in all tumors (8.260 vs. 1.796). However, p53 protein overexpression was not an independent indicator of survival in all tumors as well as distal tumors (p = 0.1918 in all tumors, p = 0.0607 in distal tumors). In proximal tumors, p53 mutation was not an independent indicator (p = 0.6673). We think that p53 mutation is a very useful prognostic indicator when distal colorectal cancers are considered.