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Background: Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status., Methods: Ninety-one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric-repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors., Results: Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P=0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P=0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P=0.04; relative risk, 6.48). Among patients with tumors classified as telomerase-positive, telomere length ratios (the ratio of tumor tissues to normal tissues)

Background: Loss of heterozygosity (LOH) of chromosome 3p has been observed commonly in carcinomas of various tumor tissues, including colorectal carcinoma (CRC). Because there is no report analyzing 3p deletions in relation to patient prognosis in CRC, the authors investigated the prognostic value of LOH on 3p in 87 patients with sporadic CRC., Methods: DNA samples from tumor and nontumor tissues were amplified by using polymerase chain reaction (PCR) and were analyzed for LOH on 3p using four different polymorphic human dinucleotide repeat DNA markers that map on this chromosome arm. The correlations with prognosis were established by the Kaplan-Meier method, and the Cox proportional hazards model was used to identify which independent factors jointly had a significant influence on patient survival., Results: Overall, allelic losses were detected in 19.5% of the patients evaluated. Only considering informative tumors, the data indicated that LOH was observed in 17 of 71 (29.4%) informative cases. Results from survival analysis showed a significant correlation between this molecular abnormality and both overall survival and disease free survival (P = 0.02 and P = 0.0005, respectively). The worst prognosis was found for the group of patients with LOH at 3p23: This alteration was an independent prognostic factor according to Cox multivariate analysis., Conclusions: This study is the first to demonstrate the prognostic significance of LOH at chromosome arm 3p for patients CRC and may help to identify patients who need an intensive postoperative follow-up protocol., (Copyright 2000 American Cancer Society.)

Background: The use of new prognostic factors as guidelines for the indication of treatment ancillary to surgery has been advocated for patients with nonsmall cell lung carcinoma (NSCLC). This article is an analysis of the prognostic information derived from determination of tumor-tissue cytosolic concentration of CA 125 tumor-associated antigen (CA 125), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC) in patients with NSCLC., Methods: Tumor samples were obtained from 97 patients who successfully underwent surgery for NSCLC with curative intent. CA 125 and CEA were determined by enzyme immunoassay. SCC was determined by radioimmunoassay. The relationship between the tumor-tissue marker level and survival or likelihood of disease free survival was analyzed., Results: Thirty-month survival post-treatment in patients registering CA 125 levels less than 26 U/mg was 68%, versus 30% among patients with levels of CA 125 greater tha 26 U/mg (P < 0.005). For SCC, these values were 57% and 39%, respectively (P = 0.07). No significant difference was seen for CEA (60% versus 44%; P = 0.3). Patients whose tumors had CA 125 levels lower than cutoff recorded a disease free survival rate of 61% versus 29% (P < 0.001); with SCC, likelihood of remaining free of tumor recurrence was 55% versus 34% (P < 0.05). Again, no significant difference was seen for CEA (49% versus 45%; P = 0.5). For CA 125 and SCC, the relationship between marker level and outcome held only with the most favorable histologic types. For CA 125 however, this relationship also held for Stage I tumors (P < 0.005)., Conclusions: Ascertainment of concentrations of CA 125 and SCC in tumor tissue is useful parameter in the determination of postoperative prognosis for patients with NSCLC.

Background: Cytokines are produced by tumor cells in vitro, but evidence for in vivo increased production of cytokines in cancer patients is controversial. Conversely, nitric oxide (NO) is implicated increasingly in the mediation of cytokine effects. Lung cancer patients may show an increased local production of cytokines and NO, and chronic paracrine exposure of epithelial lung cells to these medicators may influence the production of surfactant phosphatidylcholine., Methods: The presence of the cytokine tumor necrosis factor (TNF alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6), as well as NO, cyclic guanosine 3'5' monophosphate (cGMP) and phosphatidylcholine levels in bronchoalveolar lavage fluid (BLF) of lung cancer patients were investigated. Bronchoalveolar lavage fluid was obtained from 30 male smokers: 22 patients with squamous cell lung cancer and 8 subjects without cancer., Results: When compared with the control subjects, the cancer patients had elevated BLF levels of TNF alpha (1.58 +/- 0.47 vs. 0.04 +/- 0.02 pg/microgram protein, P < 0.001), IL-6 (1.39 +/- 0.29 vs. 0.04 +/- 0.02 pg/microgram protein, P < 0.001), and NO2-/NO3- (23.3 +/- 5.6 vs 1.1 +/- 0.6 nmol/mg protein, P < 0.001). However, phosphatidylcholine levels were lower in those with cancer than in the control subjects (3.0 +/- 1.2 vs. 24.8 +/- 6.4 micrograms protein, P < 0.001)., Conclusions: The results showed in vivo production of inflammatory cytokines in human lung cancer and increased tumor-associated NO production, as suggested by increased levels of nitrite/nitrate in the BLF. A decreased phosphatidylcholine content in the BLF also was found in patients with lung cancer.

Background: The cytosolic content of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC), CA 125, and CA 50 antigens in non-small cell lung cancer (NSCLC) is analyzed in this study. The aim was to ascertain the relationship between tumor marker content and the clinicopathologic aspects of this neoplasm., Methods: Lung tissue samples were obtained at the time of surgery from 75 patients with NSCLC patients (samples of tumor and unaffected tissue) and 29 subjects with idiopathic pneumothorax. All determinations were performed on cytosols obtained from lung specimens. CEA and CA 125 were determined by enzyme immunoassay, SCC antigen by radioimmunoassay, and CA 50 by fluoroimmunoassay. Tumor marker content was analyzed by TNM stage, histologic type, tumor grade, and number of atypias., Results: The concentration of the four markers was significantly higher in cytosol obtained from neoplastic tissue. Frequency of elevated levels of CEA was higher in adenocarcinoma (87% cases expressing high levels of the marker), SCC antigen in epidermoid carcinoma (65% expressing high levels), and CA 125 in large cell carcinomas (100% expressing high levels). No association was found between TNM stage and cytosol concentration for any of the four markers. CEA exhibited significantly greater concentration in well differentiated tumors, whereas this was true of CA 125 in poorly differentiated tumors. CA 125 content was higher in tumors with more atypia., Conclusions: Cytosolic quantification of tumor markers may be an adjuvant mechanism to evaluate histologic subtypes of non-small cell lung cancer and identification of tumors with poorly differentiated features.

Background: The serum levels of CA 125 tumor-associated antigen in patients with lung cancer have been previously related to TNM stage, histologic type, and survival rate. In the current study, the prognostic information provided by the CA 125 antigen assay was analyzed., Methods: Preoperative serum of CA 125 antigen was determined in 137 patients with non-small cell lung cancer. The assay was performed by means of a solid-phase enzyme-immunoassay test. The influence of CA 125 serum level on postoperative outcome was studied by a multivariate analysis, performed with Cox's proportional hazards regression model., Results: Patients whose initial CA 125 level was higher than 15 U/ml had a 3.25-fold greater likelihood of relapse (95% confidence interval [CI], 1.7-6.21) (P < 0.001) and a 4.27-fold greater likelihood of deaths (95% CI, 2.42-7.55) (P < 0.001) due to cancer than patients with lower values. For patients with serum levels over 15 U/ml, the 36-month survival rate posttreatment was lower (67% versus 20%) (P < 0.001), as was the disease-free rate (64% versus 13%) (P < 0.001). After adjustment for TNM stages, histologic type, sex, and age, patients with CA 125 values over 15 U/ml continued exhibiting higher risk of relapse (hazard ratio, 2.2; 95% CI, 1.04-4.69) (P = 0.04) and higher risk of death (hazard ratio, 2.42; 95% CI, 1.29-4.54) (P = 0.006)., Conclusions: CA 125 is an independent prognostic factor of survival and tumor relapse in non-small cell lung cancer. The preoperative serum level of CA 125 antigen is inversely correlated with the outcome figures. The authors suggest that CA 125 be included in any future multifactorial analysis of survival.

Serum CA 125 levels were evaluated in 130 healthy subjects and 133 patients with untreated pulmonary lesions. These were 33 patients with benign pulmonary conditions and 100 with lung cancer. The mean concentration of CA 125 was higher in patients with lung cancer (37 +/- 81 U/ml) than in those with nonmalignant disease (4.2 +/- 5.7 U/ml) (P less than 0.01). In the healthy control group CA 125 concentrations were significantly lower (0.63 +/- 1.5 U/ml) (P less than 0.001). In patients with lung cancer the concentration of this tumor marker was related to the tumor-node-metastasis (TNM) stage. At a cut-off value of 15 U/ml, CA 125 had a sensitivity of 44%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 65% with respect to healthy subjects; in patients with benign pulmonary conditions, these values were 44%, 94%, 94%, and 31%, respectively. At this cut-off value, a correlation between the respectability prognosis and the likelihood of survival 24 months posttreatment was observed. These findings suggest that CA 125 can be used as an adjunctive test in the management of patients with lung cancer patients.

Serum zinc (Zn), copper (Cu), and the Cu/Zn ratio were evaluated in 84 patients with pulmonary lesions before surgery and in 100 healthy normal controls. There were 20 patients with benign and 64 with malignant lung tumors. Only the mean (+/- SD) Cu/Zn ratio was significantly higher in malignant tumors (2.24 +/- 0.78) than in benign tissue (1.63 +/- 0.33) (P less than 0.001). In the normal group, the Cu/Zn ratio was significantly lower (1.43 +/- 0.29). Patients with advanced disease (Stage III) had higher Cu/Zn ratio than patients in Stages I and II (2.65 +/- 0.86 versus 1.9 +/- 0.27) (P less than 0.001). At a cutoff value of 1.72, Cu/Zn ratio had a sensitivity of 89%, specificity of 84%, positive predictive value of 78%, and negative predictive value of 92% between controls and lung cancer patients. Between lung cancer patients and patients with benign pulmonary lesions the aforementioned values were 89%, 70%, 90%, and 70% respectively. A correlation between increasing Cu/Zn ratio and tumor extension and postoperative survival was observed. These findings suggest that Cu/Zn ratio may be used as a diagnostic test in lung cancer patients.