Peripheral benzodiazepine receptors in androgen sensitive dunning rat prostatic adenocarcinoma

Several lines of evidence implicate the ras oncogene in tumorigenesis. However, changes in ras oncogene is uncommon in prostate cancer. We evaluated tumors from 55 patients with metastatic prostate cancer (50 lymph nodes, 5 bone metastases), 10 patients with localized cancers and 35 diethylstilbestrol treated primary tumors. Also, 15 patients with benign prostatic hyperplasia and 23 with prostatic intraepithelial neoplasia (PIN) were investigated for ras p21 expression. Avidin biotin immunoperoxidase was used on formalin-fixed, paraffin-embedded tissues with the Pan-ras (Ab-1) monoclonal antibody. Antibody titration demonstrated expression of ras p21 in none of the benign, PIN or DES-treated primary tumor specimens. However, 30% of untreated primary tumors and 94.5% of metastatic tumors (94% of lymph node metastases, 100% of bone metastases) showed expression (p=0.00002). Semi-quantitative evaluation of ras protein expression revealed a significant correlation with Gleason score in lymph node metastases (p=0.001). This study suggests a possible role of ras oncogene in prostate cancer progression, metastasis and androgen independency.     

P53 mutation analysis of colorectal liver metastases: relation to actual survival, angiogenic status, and p53 overexpression.

PURPOSE: To correlate TP53 mutations with angiogenic status of the tumor and prognosis after liver surgery in patients with colorectal liver metastases and to correlate immunohistochemical staining of p53 protein with TP53 gene mutations. EXPERIMENTAL DESIGN: Tumors of 44 patients with surgically treated colorectal liver metastases were analyzed for (a) TP53 mutations using denaturing gradient gel electrophoresis followed by sequencing, (b) microvessel density using the hot spot overlap technique, (c) apoptotic rate in tumor cells and endothelial cells of tumor microvessels using double immunostaining for anti-cleaved caspase 3 and anti-CD34, and (d) expression of p53 protein using immunohistochemistry. RESULTS: TP53 mutations were detected in 36% of the metastases and occurred more frequently in liver metastases from left-sided colon tumors than from right-sided colon tumors (P = 0.04). In metastases with TP53 mutations, microvessel density was higher compared with tumors with wild-type p53. Endothelial cell apoptosis was not different in tumor microvessels from TP53-mutated versus nonmutated tumors. The 5-year actual survival was not influenced by TP53 mutational status, microvessel density, or endothelial cell apoptotic rate of the tumors. Based on immunohistochemical p53 overexpression, the positive and negative predictive values of TP53 mutations were 61% and 82%. CONCLUSIONS: In patients with surgically treated colorectal liver metastases, TP53 mutations and angiogenic status did not influence prognosis. Immunohistochemistry is not a reliable technique for detecting TP53 mutations.     

Expression of metallothionein in colorectal cancers and synchronous liver metastases

The aim of this study is to clarify whether the expression of metallothionein (MT) is related with the malignant potential in primary colorectal cancer and/or synchronous liver metastasis. Immunohistochemical staining for MT was performed on the specimens of adenocarcinoma of the colon and rectum and its liver metastases in 34 patients treated with curative surgery, respectively. Expression of MT was compared with clinicopathological variables and patient survival. In patients with primary colorectal cancer, positive expression was found in 7 of 34 (20.6%) patients, but MT was not detected in any of the cases of liver metastases (0%; p = 0.0111). In the primary tumor, positive MT expression was significantly associated with a higher degree of lymph node involvement (mean +/- SD: 48.4 +/- 33.8 vs. 18.6 +/- 24.4% in MT-positive and MT-negative tumors, respectively; p = 0.0122). The survival rate in the patients with MT-negative tumors was significantly better than that in those with MT-positive tumors as primary sites (p = 0.0198). MT expression in colorectal cancer may be a potential marker affecting lymph node metastases and may be a predictor of a poor prognosis, particularly in patients with synchronous liver metastases.     

Liver fatty acid-binding protein is a new prognostic factor for hepatic resection of colorectal cancer metastases.

BACKGROUND AND OBJECTIVES: Liver fatty acid-binding protein (L-FABP) is reported as a biological marker for enterocytic differentiation. We evaluated the prognostic value of L-FABP expression for patients undergoing hepatic resection of colorectal cancer metastases. METHODS: The study group comprised 68 patients who underwent hepatic resection for colorectal cancer metastases between 1982 and 1996 at Niigata University Medical Hospital, Niigata, Japan. L-FABP expression was immunohistochemically studied in metastatic liver tumors and their primary colorectal cancers. The relationship between L-FABP expression and patient prognoses was statistically analyzed. RESULTS: L-FABP was positively stained in 56% (38/68) of liver metastases from colorectal cancers and in 56% (38/68) of their primary tumors. Of 68 cases, 54 (79%) showed similar immunohistochemical findings between primary and metastatic tumors. Patients with L-FABP-positive liver metastases showed better prognosis than patients with L-FABP-negative metastases (P = 0.046). L-FABP expression in primary colorectal cancers more significantly (P = 0.009) affected long-term survival after hepatic surgery. Multivariate analysis revealed that the prognostic effect of L-FABP expression in primary colorectal cancers was exerted independently and that its impact was larger than conventional pathological prognosticators. CONCLUSIONS: L-FABP expression is suitable for use as a new presurgical prognostic factor for patients undergoing hepatic surgery for colorectal cancer metastases.     

Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer.

PURPOSE: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopathologic and biological variables in colorectal cancers. EXPERIMENTAL DESIGN: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. RESULTS: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. CONCLUSIONS: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients.     

p73 Overexpression and angiogenesis in human colorectal carcinoma

BACKGROUND: Solid tumors requires neovascularization for growth and metastasis. Angiogenesis depends on the local balance between positive and negative effectors, the production of which can be regulated by oncogenes and tumor suppressor genes. The aim of this study was to investigate expression of p73, a gene homologous to the tumor suppressor gene p53, in colorectal cancer and its relationship to angiogenesis. METHODS: p73 expression was examined by immunohistochemistry and western blot analysis on 56 primary colon carcinomas with matched normal mucosas. Vascular endothelial growth factor (VEGF) and microvessels were highlighted using a monoclonal antibody specific to VEGF and von Willebrand factor (vWF). RESULTS: The immunoexpressions of p73 were significantly higher in the primary colorectal carcinomas than that in the matched normal mucosa (P < 0.001). Western blotting showed that 85% patients have a high level of p73 expression (more than double the normal level). A close association between p73 and VEGF expression level was observed (P = 0.016). Colorectal adenocarcinoma that expressed p73 showed significantly greater vascularity than p73-negative tumors (P = 0.012). However, no association between immunoexpression of p73 and tumor stage or differentiation was observed. CONCLUSION: These findings suggest a potential role of p73 in tumor angiogenesis.     

Thymidylate synthase protein expression in primary colorectal cancer compared with the corresponding distant metastases and relationship with the clinical response to 5-fluorouracil.

Thymidylate synthase (TS) expression in colorectal cancer metastases has been shown to predict for the clinical response to 5-fluorouracil. Because primary tumors may easily provide accessible sources of tissue for marker analysis, we have investigated the stability of TS expression between primary colorectal cancer and the corresponding distant metastases and compared their relative ability to predict response to chemotherapy on a series of 27 patients homogeneously treated with biochemically modulated fluorouracil for advanced disease. By immunohistochemistry, high levels of TS expression were observed in 19 of 27 (70%) primary tumors and in 13 of 27 (48%) metastatic samples. Overall, TS levels observed in primary tumors did not correlate with those measured in the corresponding metastases (r = 0.30, P = 0.13), with higher TS levels in primary tumors in 8 of 10 discordant cases. Accordingly, the degree of TS immunoreactivity was significantly higher in primary tumors compared with the corresponding metastases (mean TS score 3.8; median, 4 versus 2.8; median 3; P = 0.001). Response rates after chemotherapy for metastatic disease were similar for patients with low and high TS levels in their primary tumors (37% versus 53%, P = 0.47). In contrast, response rates were 71% and 23% in patients with low and high TS in metastatic samples (P = 0.012), respectively. In summary, TS levels measured in primary colorectal cancer do not reflect those observed in the corresponding metastases and cannot be used to predict their response to chemotherapy. The basis for the higher TS content of primary colorectal cancer compared with the corresponding metastases needs clarification.     

Analysis of the p53/BAX pathway in colorectal cancer: low BAX is a negative prognostic factor in patients with resected liver metastases.

PURPOSE: To determine the prognostic value of the central downstream apoptosis effector BAX in relation to its upstream regulator p53 in R0-resected hepatic metastases of colorectal cancer. PATIENTS AND METHODS: Retrospective analysis of 41 patients who underwent potentially curative resection of liver metastases from colarectal cancer was performed. Tumor DNA was screened for p53 mutations by single-stranded conformational polymorphism polymerase chain reaction and for BAX frameshift mutations by fragment length analysis. Protein expression of BAX, p21, and p53 was investigated by immunohistochemistry. RESULTS: Overall median survival was 40.2 months. Tumors with BAX frameshift mutations were considered microsatellite mutator phenotype-positive and were excluded from further prognostic analyses. Patients with high BAX protein expression had a median survival of 53.6 months compared with 35.4 months for patients with low BAX expression (P < .05). The negative prognostic value of low BAX expression was more evident in those patients with wild-type p53 (median survival, 54.0 v 23.3 months for BAX-negative tumors; P < .01). Low BAX expression was an independent negative prognostic marker in multivariate regression analysis for all patients independent of the p53 status (relative risk, 3.03, P = .03), especially for p53 wild-type tumors (relative risk, 8.21; P = .0095). CONCLUSION: We conclude that low BAX expression is an independent negative prognostic marker in patients with hepatic metastases of colorectal cancer. The best survival was seen in patients with an intact p53-to-BAX pathway; ie, wild-type p53- and BAX-positive tumors. Thus, analysis of apoptosis signaling pathways (here, p53 in concert with its downstream death effector, BAX) might yield more prognostic power in future studies as compared with analysis of single genes such as p53 alone.     

Clinicopathological significance of Nup88 expression in patients with colorectal cancer

OBJECTIVE: The nucleoporin Nup88 is overexpressed in a series of human malignancies, however, its clinicopathological significance has not been studied. Our aims were to analyze Nup88 expression in normal mucosa, primary tumors and metastases from colorectal cancer patients and further to identify relationships of Nup88 expression with clinicopathological and other factors. MATERIALS AND METHODS: Using immunohistochemistry, we investigated Nup88 expression in 198 primary colorectal tumors, 96 normal mucosa samples and 35 lymph node metastases. RESULTS: The results showed that the intensity of Nup88 expression increased from the normal mucosa to the primary tumors (p < 0.0001) and tended to increase from the primary tumors to the metastases (p = 0.15). Both primary tumors and metastases presented stronger expression in the invasive margin and vascular-invaded areas. Nup88 expression was positively related to distal tumor location (p = 0.01), infiltrative growth pattern (p = 0.04) and higher proliferative activity (p = 0.04) and reversely to the grade of differentiation (p = 0.02) and apoptosis (p = 0.049). Strong expression of Nup88 predicted a worse outcome in the patients with distal tumors during the follow-up period of up to 3 years (p = 0.02). CONCLUSIONS: It seems that overexpression of Nup88 was involved in the tumorigenesis and aggressiveness of colorectal cancers, and Nup88 may be used as a prognostic factor in patients with distal tumors.     

Expression of the deleted in colorectal cancer gene is related to prognosis in DNA diploid and low proliferative colorectal adenocarcinoma.

PURPOSE: Whether or not the deleted in colorectal cancer (DCC) gene is implicated in metastases or in predicting prognosis in patients with colorectal cancer has not previously been substantiated. Our aims were to investigate DCC expression in primary colorectal cancers and in metastases to identify any prognostic significance. PATIENTS AND METHODS: DCC expression was examined immunohistochemically in 195 primary colorectal adenocarcinomas and in 23 paired primary tumors and lymph node metastases. DNA content and S-phase fraction were measured by flow cytometry. RESULTS: The absence of DCC expression was observed in 55 primary tumors (28%). DCC negativity was significantly related to poor prognosis in patients with DNA diploid tumors (P =.03) and those with a low S-phase fraction (< 5%, P =.02) but not in patients with nondiploid tumors or those with a higher S-phase fraction. Furthermore, DCC expression retained its prognostic significance in the diploid subgroup after adjusting for sex, age, site, stage, growth pattern, and differentiation (P =.01). DCC expression was similar in primary tumors and their metastases. CONCLUSION: The absence of DCC predicted a poor outcome in the patients with diploid tumors and those tumors with a low S-phase fraction. Immunohistochemistry may be considered as a practical test to assess prognosis in this subgroup of patients.     

Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases.

AIMS: The liver is a frequent site of metastases from colorectal cancer. While these lesions are potentially amenable to surgical resection, they are usually very aggressive, and recurrence is frequent. Mutations of the proto-oncogene K- ras are thought to impart a strong growth signal to tumour cells and are closely associated with the development of malignancies of the colon and rectum. Hepatic metastases from colorectal cancer have notably elevated proliferative rates. The present study was performed to investigate the relationship between proliferation or K- ras mutation and prognosis following curative resection of colorectal liver metastases. METHODS: Colorectal liver metastases from 41 patients undergoing curative hepatic resection were examined for proliferation status and presence of K- ras mutations. The proliferative activity was assessed by Ki-67 immunohistochemistry. DNA from the same tissue samples was screened for point mutations in codon 12 of the K- ras gene using a novel microplate-based allelic-specific hybridization assay. Ki-67 scores and K- ras status were then related with patient survival as determined through retrospective analysis. RESULTS: Median survival was 40 months. Patients with high Ki-67 scores (> or = 50%) had significantly shorter median survival compared with those with low scores (30 vs 44 months, log-rank P=0.02). A high Ki-67 score was an independent negative prognostic factor by multivariate regression analysis (relative risk=3.04, P=0.036). K- ras point mutations were detected in 6/41 patients (15%), but mutational status did not correlate with Ki-67 score or survival. CONCLUSIONS: These findings suggest that the tumour proliferative index is a useful predictor of aggressive tumour behaviour and an indicator of patient survival. The presence of K- ras mutations does not appear to correlate with tumour proliferation status or patient survival. Copyright Harcourt Publishers Limited.     

Expression of MAC30 protein is related to survival and biological variables in primary and metastatic colorectal cancers

MAC30 is highly expressed in several types of tumors including colorectal cancers, however, its clinicopathological and biological significance in colorectal cancers is currently not known. The aim of our study was to investigate MAC30 expression in distant normal mucosa, adjacent normal mucosa, primary tumors and metastases of colorectal cancer, and to determine the relationship between MAC30 expression and clinicopathological and biological variables. MAC30 expression was immunohistochemically examined in distant normal mucosa (n = 54), adjacent normal mucosa (n = 123), primary tumors (n = 217) and lymph node metastases (n = 56) from colorectal cancer patients. MAC30 cytoplasmic expression was increased from distant normal mucosa to primary tumor and to metastasis (p < 0.0001-0.04). Furthermore, 40% primary and 37% metastatic tumors showed stronger cytoplasmic expression of MAC30 at the tumor invasive margins compared to inner tumor areas. Strong cytoplasmic expression of MAC30 in the metastasis was related to a poor prognosis (p = 0.04). MAC30 cytoplasmic expression was positively related to expression of proliferating cell nuclear antigen (p = 0.04), p53 (p = 0.04), nucleoporin 88 (p = 0.001), legumain (p = 0.004) and particularly interesting new cysteine-histidine rich protein (p = 0.004). However, MAC30 expression in the nucleus and stroma did not have any clinicopathological and biological significance (p > 0.05). In conclusion, MAC30 protein may play a role in development of colorectal cancer, and can be considered as a prognostic factor.     

Long-term survival and tumor 5-FU sensitivity in patients with stage IV colorectal cancer and peritoneal dissemination

Among 125 patients with peritoneal dissemination (P1-3) of colorectal cancer, including those with other synchronous metastases, the 5-year overall survival (OS) rate was 13.3% for P1 patients (n=30), 12.8% for P2 patients (n=39), and 1.8% for P3 patients (n=56) (P1 vs. P2, p=N.S.; P2 vs. P3, p=0.02; P1 vs. P3, p=0.001), while the median survival time (MST) was 12.0, 14.1, and 3.1 months, respectively. The 5-year OS rates for patients who had peritoneal dissemination without other metastases were 17.6% (n=17), 12.5% (n=19), and 3.4% (n=28) (P1 vs. P2, p=N.S.; P2 vs. P3, p=N.S.; P1 vs. P3, p=0.039), while the MST was 25.1, 15.1, and 12.5 months, respectively. In the P3 short survival group (SSG; n=13), TS expression was high in 7.7% (1/13) and low in 92.3% (12/13) of tumors, while DPD expression was high in 38.5% (5/13) and low in 61.5% (8/13) of tumors. In the P3 long survival group (LSG; n=15), the corresponding values were 80.0% (12/15), 20.0% (3/15), 33.3% (5/15), and 66.7% (10/15). High TS and low DPD expression was found in only 7.7% (1/13) of the SSG tumors vs. 46.7% (7/15) of the LSG tumors (p=0.028). These results suggest that the prognosis of stage IV colorectal cancer with P3 peritoneal dissemination is extremely poor. In addition, patients fitting the SSG criteria are unlikely to respond to treatment with 5-FU+LV, and may need combination chemotherapy using CPT-11 and/or L-OHP.     

The Significance of Sidedness in Patients with Metastatic Colorectal Cancer Treated with Triplet First-line Chemotherapy

Background: Recent data have shown that right-sided colon cancer carries poorer prognosis compared to left-sided tumors. This study was aimed to evaluate the progression-free survival, overall survival of patients with metastatic colon cancer of right-sided versus left-sided primaries treated with triplet chemotherapy regimen. Methods: The medical records of patients with metastatic colorectal cancer treated on phase I-II trial of combination Irinotecan, oxaliplatin, capecitabine, and bevacizumab were reviewed for sidedness of the primary. The analysis was performed for progression-free survival and overall survival according to the sidedness and other known prognostic factors. Results: Out of 53 patients treated with triplet therapy, 11 had right sided and 42 had left-sided primaries. The median age for right-sided primaries was 46 (range 24-55) compared to 53 (range 32-74) in left-sided primaries. Median progression-free survival was 14 months for right vs 18 months for left sided tumors (Hazard ratio 0.72, 95% confidence interval 0.27-1.88, p=0.492) and median overall survival was 21 months for right vs 29 months for left sided tumors (Hazard ratio was 0.86, 95% CI 0.32-2.26, p=0.752). Conclusion: First-line triplet chemotherapy may overcome the difference in prognosis between right sided and left sided primaries in metastatic colorectal cancer. A larger analysis is warranted.     

Polymorphism of the p73 gene in relation to colorectal cancer risk and survival

The results regarding a GC/AT polymorphism in the p73 gene in relation to cancer risk are inconsistent, and the significance of loss of heterozygosity (LOH) of the gene is unclear. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. 179 patients with colorectal cancer and 260 healthy controls were genotyped for the polymorphism by PCR-restriction fragment length polymorphism (RFLP). Fifty informative cases were examined for LOH in tumours. Immunohistochemistry was performed on distant (n = 42) and adjacent normal mucosa (n = 33), primary tumour (n = 6 9) and lymph node metastasis (n = 12). The frequencies of the genotypes were 63% for wild-type (GC/GC), 30% for heterozygotes (GC/AT) and 7% for variants (AT/AT) in patients, and 62, 36 and 2% in controls, respectively. The frequencies of the genotypes in the patients and controls were significantly different (P = 0.02). The patients carrying the AT allele had a better prognosis than those with the GC/GC genotype (OR = 0.42, 95% CI = 1.15-5.02, P = 0.02). No LOH was observed at the p73 locus. Expression of p73 protein was increased from normal mucosa to primary tumours (P = 0.02), but was not significantly changed between primary tumours and metastases (P = 1.0). In conclusion, the AT/AT homozygotes may have a greater risk of developing colorectal cancer, while the patients who carried the AT allele had a better prognosis.     

大肠癌 p27蛋白表达与 DNA倍体分析的研究

背景与目的细胞周期调控的改变存在于绝大多数肿瘤中,因此可以认为肿瘤是一类细胞周期疾病.p27蛋白是细胞周期负性调控因子的主要成员,同时也是肿瘤的重要预后因子.p27蛋白表达下降及亚细胞定位改变在大肠癌发展中的意义尚不清楚.大肠癌中 p27蛋白表达与 DNA倍体关系尚未见报道.本实验研究大肠癌 p27蛋白表达与临床病理特征及 DNA倍体分析的关系.方法应用免疫组化方法检测 p27蛋白在 40例大肠癌中的表达水平,同时应用病理图像 DNA测量系统对癌组织进行倍体分析.结果p27蛋白在大肠癌中的高表达率为 62.5%(25/40),低表达率为 37.5%(15/40),p27蛋白低表达与大肠癌分化程度低显著相关(P< 0.05).除胞核着色外,32.5%(13/40)的大肠癌出现胞浆免疫阳性反应.p27蛋白胞浆表达与 Dukes分期晚(P< 0.01)、易发生淋巴结转移显著相关(P< 0.05).p27蛋白低表达组 DNA多倍体细胞检出率(22.2± 11.3)% 明显高于 p27蛋白高表达组 [(8.0± 7.7)%,P< 0.001]. 结论p27蛋白表达的下降及亚细胞定位改变促进大肠癌的发展 ; 抑制 DNA多倍体形成可能是 p27蛋白的抑癌机理之一.     

Bcl-2 expression is a prognostic factor in the subgroups of patients with colorectal cancer

The prognostic significance of Bcl-2 expression in colorectal cancer has been intensively studied, however, the results were controversial in the whole group of colorectal cancer patients. We proposed that one of the main reasons for such controversial results may be that Bcl-2 played variable roles in the subgroup of patients. We, therefore, investigated the prognostic importance of Bcl-2 expression by using immunohistochemistry in the various subgroups of 147 patients with colorectal cancer. Among these tumours, 85 (58%) expressed Bcl-2 protein and 62 (42%) were negative. Bcl-2 expression was positively related to DCC expression (p=0.0002). Survival analyses in the subgroups of the patients showed that lack of Bcl-2 expression was related to a worse prognosis in the male patients (p=0.02) but not in female patients (p=0.53), in the patients with DNA diploid tumours (p=0.005) not in the patients with non-diploid tumours (p=0.46), and in the patients with ras negative tumours (p=0.01) not in the patients with ras positive tumours (p=0.25). Bcl-2 expression was not related to prognosis in the total group of the patients (p=0.20). In conclusion, Bcl-2 protein may play variable prognostic roles in the subgroups of the patients with colorectal cancer. Analysis of Bcl-2 expression in the tumour may be of value in predicting prognosis and therapeutic response.     

Detection of Tumor DNA in Serum of Colorectal Cancer Patients

We previously found p16 promoter methylation in DNA in the sera of 13 colorectal cancer patients out of 44 (30%) whose tumor DNA exhibited the methylation, using methylation-specific PCR (MSP). To examine whether the cancer detection rate could be improved by using a different tumor marker, we examined the K- ras status in 90 colorectal cancer patients using a mismatch ligation assay. Among the 31 patients showing K- ras gene mutations in their tumors, the same mutations were observed in serum DNA of 11 patients (35%). Among the 90 patients, 63 showed tumors positive for K- ras mutation or p16 promoter methylation, or both, and 22 had serum DNA positive for one or both. K- ras mutation was found even in serum DNA of patients with Dukes A cancer, suggesting that colorectal cancer might be detected even in patients without symptoms by using this ligation assay.     

Prognostic value of LISCH7 mRNA in plasma and tumor of colon cancer patients.

PURPOSE: LISCH7 is a gene potentially regulated by p53 that is up-regulated in metastasis development. Our hypothesis was that the expression of LISCH7 in primary colorectal tumors determined certain characteristics of the tumors, as well as their behavior, and that its identification in plasma could serve as a prognostic marker. EXPERIMENTAL DESIGN: We tested this hypothesis in a series of 115 tumors and normal tissues and in 83 plasmas from patients with sporadic colorectal carcinomas, as well as in 20 healthy control plasmas in which the expression levels of the gene were measured by real-time PCR. The expression data were contrasted with clinicopathologic variables. RESULTS: Although LISCH7 expression was not detected in any control plasma samples, it was positive in 25 (30.1%) plasmas from patients (P = 0.002). LISCH7 mRNA in plasma was significantly associated with the pathologic stage (P = 0.019), with lymph node metastasis (P = 0.008) and with vascular invasion (P = 0.005). Expression was not detected in any normal tissues but was detected in 80 tumor tissues, with a clear association found with vascular invasion (P = 0.027). Moreover, we show that LISCH7 was specifically expressed by the epithelial tumor cells. The adjusted overall survival study showed independent prognostic values for LISCH7 expression levels in tumor tissues (hazard ratio, 3.45; 95% confidence interval, 1.19-9.98). CONCLUSIONS: Our results suggest that LISCH7 is a good tumor marker whose expression levels could be considered as a poor prognosis factor in human colon cancer. Furthermore, plasma is suggested as a feasible source of nucleic acids for subsequent noninvasive prognostic studies.