Copper, zinc, magnesium, calcium and iron were measured in serum and lung tissue – tumor mass and histologically nonneoplastic tissue – from lung cancer patients and compared with serum concentrations in healthy subjects and control lung tissue obtained from patients with nonmalignant lung disease. Lung cancer patients showed a significant increase in serum Cu and Cu/Zn ratio levels and decrease in serum Zn and Fe concentrations. These findings were correlated with TNM stage of the disease, but not with histologic type of tumor. Malignant lung tissue showed a higher level of Cu, Ca, Mg, and Cu/Zn ratio and lower Zn level than that found in control samples, as well as an increase in Cu, Mg and Cu/Zn ratio concentrations with regard to histologically nonneoplastic tissue samples from the same patient. Tissue concentration of trace metals was not significantly influenced either by histologic type of tumor or clinical TNM stage. Significant correlation coefficients between serum and tissue trace metal levels were not found.

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 (kSD) Cu/Zn ratio was significantly higher in malignant tumors (2.24 * 0.78) than in benign tissue (1.63 3~ 0.33) (P < 0.001). In the normal group, the Cu/Zn ratio was significantly lower (1.43 k 0.29). Patients with advanced disease (Stage 111) had higher Cu/Zn ratio than patients in Stages I and I1 (2.65 k 0.86 versus 1.9 k 0.27) (P < 0.001). At a cutoff value of 1.72, Cu/Zn ratio had a sensitivity of 89%, specificity of 841, 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. Cancer 63:726-730, 1989.

Summary Risk of death and risk of recurrence in 108 potentially curable non-small-cell lung cancer patients were analysed with respect to TNM stage, histological type and carcinoembryonic antigen (CEA), CA125 antigen and squamous cell carcinoma antigen (SCC) levels in serum and cytosol. CA125 and CEA levels were closely related to outcome figures. Multivariate analyses indicated that TNM stage and histological type had the best predictive power, but serum and cytosolic CA125 and serum CEA contained additional, independent prognostic information. Predictive information drawn from serum and cytosolic levels proved mutually complementary. We conclude that CA125 and CEA complement TNM classification and histological type for the purpose of quantifying risk of death or recurrence.Keywords: carcinoembryonic antigen; CA125; squamous cell carcinoma antigen; lung cancer; prognostic factor; survivalThe tumour -node-metastasis (TNM) classification system is the cornerstone for planning therapy options in patients with non-small-cell lung cancer (NSCLC) (Bains, 1991). Such staging of tumour spread is the best available prognostic factor. However, its predictive power is limited. Differences may be seen between expected and actual outcome after curative resection among patients within the same TNM category of risk. Efforts are under way to confirm the possibility that long-term results or response to treatment may be partially based on biological characteristics inherent in tumour cells (Carney, 1991). Methods for the description of biological tumour aggressiveness are rapidly expanding (Carney, 1991;Lee and Hong, 1992).Owing to their low sensitivity and specificity, tumour markers have, until now, played a less important role in the diagnosis and management of NSCLC than has been the case with most other common cancers (Bergman et al., 1993;Strauss and Skarin, 1994;Jarvisalo et al., 1993 (Gail et al., 1984;Sanchez et al., 1994), guiding follow-up after surgical treatment (Diez et al., 1995) and monitoring response to chemotherapy in advanced disease (Shinkai et al., 1986;Spiridonis et al., 1995). CA125 was initially described as an ovarian cancer-associated antigen, and has recently been assayed in NSCLC. In a previous study we reported that serum levels of CA 125 provide independent information on survival and tumour relapse in patients undergoing curative surgical treatment for NSCLC (Diez et al., 1994a Analysis of tumour marker expression in NSCLC tumour tissue has not been reported as frequently. In a previous study we observed that cytosolic concentration of CEA, SCC and CA125 is a particular and distinctive characteristic of each histological type, something which could aid pathological classification (Picardo et al., 1994). In addition, high CEA plus high CA125 content allows for identification of the large-cell carcinoma histological subtype (Picardo et al., 1994). In our opinion, this kind of study could lead to a better understanding of the relationship between tumour marker and the biological features of the neop...

The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), locoregional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lungcancer recurrence. They can add useful information regarding the complex nature of prognosis. Prognosis for non-small cell lung cancer (NSCLC) has remained disappointing over the last decades, even in localized stages that are amenable to curative surgery. 1 Recurrence rates among patients with resectable NSCLC are substantial, 2-4 and only around 50% of them will be alive after 5 years. 5 The clinical or pathologic TNM staging (T, primary tumor; N, regional lymph nodes; M, distant metastasis) does not always provide a satisfactory explanation for differences in relapse and survival. It is of major importance, however, to be able to anticipate a bad prognosis to prescribe an active chemotherapy or radiotherapy adjuvant program. 6,7 In this context, a large number of articles have been published proposing the incorporation of different prognostic markers in clinical practice, 8 but the interpretation and integration of their results is hampered by methodological problems. Many studies included a low number of patients, and very few examined more than 1 or 2 markers. Furthermore, the majority are retrospective cohorts, where the quality of the follow-up is uncertain and the possibility of a selection bias cannot be ruled out. 9 Prognostic studies try to identify one or more variables that might be useful to classify a heterogeneous population into smaller subgroups with more predictable outcomes. This classification will serve to apply therapy more efficiently, avoiding...

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 solidphase 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 death (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. Cancer 1994; 73:1368–76.