Paola Marroni

CA 19‐9 and CA 50 in Benign and malignant pancreatic and biliary diseases

Serum concentrations of the CA 19‐9 and CA 50 antigens were determined in 129 patients with malignant and benign biliary and pancreatic diseases. Values for the two markers were highly correlated (P < 0.001). The concentrations of CA 19‐9 and CA 50 were positive in 84.6% and 80.7% of patients with pancreatic cancer, respectively. The overall specificity of CA 19‐9 (92.4%) was slightly higher than that of CA 50 (88.5%). The sensitivity of CA 50 (91.3%) was greater than that of CA 19‐9 (73.9%) in patients with diseases of the biliary tract. Elevated concentrations of CA 19‐9 (12.9%) and CA 50 (35.2%) were also found in a number of cases with benign disease, especially in patients with obstructive jaundice. These data suggest that both CA 19‐9 and CA 50 can be useful markers of pancreatic cancer in nonjaundiced patients. The joint use of the two markers does not yield a better diagnostic resolution than the use of either one alone.

Decline in Serum Carcinoembryonic Antigen and Cytokeratin 19 Fragment During Chemotherapy Predicts Objective Response and Survival in Patients With Advanced Nonsmall Cell Lung Cancer

The authors assessed the predictive and prognostic role of decline in the serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21‐1) during chemotherapy in patients with advanced nonsmall cell lung cancer (NSCLC).

Serum PDGF-AB in Pleural Mesothelioma

Overexpression of platelet-derived growth factor (PDGF) has been observed in lung and pleural tumors. The aim of this study was to evaluate the diagnostic and prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of subjects were studied: 93 malignant PM patients, 33 primary non small cell lung cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls, and 24 healthy controls. PDGF-AB mean concentration was higher in PM patients (45.8 ng/ml) than in high-risk controls (33.1 ng/ml) and healthy controls (26.8 ng/ml). Using the cut-off level of 49.8 ng/ml, corresponding to the mean + 2SD of PDGF-AB in healthy controls, 43% of PM patients showed positive PDGF-AB levels. Survival was evaluated in 82 PM patients. At the end of the follow-up (median 9.8 months) 80.5% of patients had died. Median survival was 13.1 and 7.9 months for patients with PDGF-AB lower and higher than the cut-off, respectively. Adjusting for age, sex, histology and platelet count, positive PDGF-AB levels were associated with lower survival (OR = 1.2, 95%CI: 0.9–1.6), even if not significantly so. In conclusion, serum PDGF may represent a useful additional parameter to prognostic factors already available for PM.

Study of pretreatment serum levels of HER‐2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma

HER‐2/neu tissue overexpression is found in nearly 15% of patients with nonsmall cell lung carcinoma and is reported to affect prognosis adversely in surgical series. However, the prognostic role of serum HER‐2/neu oncoprotein, particularly in patients with advanced lung carcinoma, remains unknown. This study was designed to assess the potential value of measuring serum levels of HER‐2/neu oncoprotein in predicting response to treatment and survival in patients with locally advanced and metastatic nonsmall cell lung carcinoma.

Serum anti-p53 autoantibodies in pleural malignant mesothelioma, lung cancer and non-neoplastic lung diseases.

Alterations of the p53 gene may lead to the production of detectable autoantibodies (p53-Abs) in cancer patients. In order to evaluate the association of p53-Abs with pleuropulmonary diseases, four groups of subjects were analyzed by ELISA for serum p53-Abs, in the framework of a molecular epidemiologic study. Two of 30 pleural malignant mesothelioma patients (MM; 6.7%) and 8/48 lung cancer patients (LC; 16.7%) were seropositive, while all 51 healthy controls (HC) were negative. Two of 55 (3.6%) at-risk controls (RC) with non-malignant respiratory diseases were positive and were not subsequently diagnosed any cancer. The difference was statistically significant between LC and RC or HC (P = 0.01), but not between MM and any other group. No correlation was found with age, sex, cancer stage or histology, cigarette smoking or occupational exposure. A longer survival (not significant) was shown in seropositive LC but not in MM. p53 expression in tumor tissue was also evaluated in a subgroup of MM. In conclusion, the presence of detectable p53-Abs in serum was associated in a statistically significant proportion of cases with LC but only occasionally with MM. The longer survival among positive LC patients and the presence of two seropositive among patients with non-neoplastic respiratory diseases should be further investigated.

Evaluation of Cathepsin D as Prognostic Predictor in Breast Cancer

Cathepsin D is an acidic lysosomal protease expressed in all cells. Some studies have shown correlations between high levels of tissue cathepsin D and poor prognosis. This paper deals with 158 cases of breast cancer in which tissue concentrations in cathepsin D, age, estrogen and progesterone receptor content, and pathological characteristics of the tumor were investigated. Tumors were considered to be cathepsin D+ when a concentration > 40 pmol/mg protein (median value in our samples) was determined. The expression of cathepsin D appears to be related to grading (p = 0.04) and lymph node status (p = 0.05). We found no significant associations among cathepsin D levels, patient age, steroid receptors and histological type. Moreover, the levels of cathepsin D have been evaluated in 9 samples of recurring or metastatic neoplasia and 11 cases of benign breast lesions. We conclude that cathepsin D may be a useful prognostic predictor in breast cancer. Further investigations are required to improve and extend the applications of this assay.

Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breast cancer patients.

Purpose: To evaluate the endocrinological and clinical activity of a new slow-release formulation of leuprolide acetate in breast cancer patients. Methods: A total of 50 pre- or perimenopausal patients with early- or late-stage breast cancer who were candidates for endocrine treatment were included in the study and randomly allocated to receive either 3.75 mg of leuprolide acetate every month or 11.25 mg of leuprolide acetate every 3 months. Patients were treated until disease recurrence or progression or for a maximum of 24 months. Treatment outcome, side effects, and serum levels of gonadotrophins, estradiol, progesterone, and Δ4-androstenedione were analyzed at different time points. Results: In all, 23 patients were allocated to the monthly formulation and 27, to the 3-monthly formulation. The median time on treatment was comparable. There was no evidence of any difference in clinical outcome or drug-induced side effects, hot flushes being recorded in about 50% of patients in both groups. Altogether, 35 patients were actively menstruating at the beginning of treatment; all of them became amenorrhoic after 3 months and remained so until treatment with leuprolide was continued, irrespective of the allocated treatment. All endocrine parameters, particularly estradiol levels, were suppressed to a similar extent. Conclusions: The present results indicate that the two formulations exert a comparable estrogen-suppressive effect and warrant further study of the 3-monthly formulation of leuprolide acetate in breast cancer patients.

Evidence for Testicular Impairment After Long-Term Treatment with a Luteinizing Hormone-Releasing Hormone Agonist in Elderly Men

Testicular responsiveness to 5,000 IU of human chorionic gonadotropin was evaluated in 14 patients with prostate cancer who were being treated with a slow-release luteinizing hormone-releasing hormone agonist for a median of 21 months. Serum testosterone response to human chorionic gonadotropin was markedly reduced in most patients, with the median level increasing from 0.25 to 1.65 nmol. per l. A second human chorionic gonadotropin test was repeated later in 5 patients who had been off treatment for a median of 6 months. Median serum testosterone levels increased to a maximum of 2.6 nmol. per l. compared to 28.2 nmol. per l. in an age-matched control group (p equals 0.008). Therefore, we conclude that long-term treatment with luteinizing hormone-releasing hormone agonists in elderly men leads to gonadal impairment that may not be as reversible as generally suggested.

Prognostic role of serum Sialyl Lewisx (CD15s) in colorectal cancer

Objective: Sialyl Lewisx (sLex) is one ligand for E selectin (CD62E), a glycoprotein that is expressed on activated endothelial cells. Adhesion mediated by endothelial E selectin and sLex expressed on human tumor cells could be relevant for the development of metastases. The aim of this study was to investigate whether or not a correlation exists between pre-operative levels of ganglioside serum sLex and disease-free interval and survival in colorectal cancer patients. Patients and Methods: Thirty Duke’s B and 52 Duke’s C patients undergoing resection for colorectal cancer were studied. The median follow-up time was 34.8 months. A pool of 57 sera from normal subjects was used as an Internal Normal Standard (INS). sLex analyses were performed by a thin layer chromatography (TLC) immunostaining technique. Results were expressed as the ratio (R) between bands of INS and bands from each neoplastic serum. Results: The median R value was 0.80 in normal subjects, 0.70 in Duke’s B patients and 1.0 in Duke’s C patients. No significant differences were detected between sLex concentrations in sera from normal and neoplastic subjects (p = 0.1). Using an arbitrary cutoff of R = 0.9, the mean disease-free interval in the whole series was 47.4 months for R <0.9 and 126.0 months for R ≧ 0.9 (p = 0.04). The survival time was 76.8 months for patients with R values <0.9 and 156.3 months for patients with R values ≧0.9 (p = 0.1). Conclusions: High serum levels of ganglioside sLex significantly correlate with a favorable prognosis and with a lower occurrence of metastases. It is conceivable that soluble sLex may compete with membrane-bound sLex in the course of interactions between activated endothelium and tumor cells that have reached the circulation.

Is Soluble Mesothelin-Related Protein an Upfront Predictive Marker of Pleural Mesothelioma? A Prospective Study on Italian Workers Exposed to Asbestos

Objective: Soluble mesothelin-related peptide (SMRP) may be useful in the diagnosis and detection of early stage mesothelioma. We investigated the SMRP upfront predictive role for mesothelioma in asbestos-exposed workers. Methods: A total of 1,715 subjects underwent a first visit and were invited for a follow-up after 1 and 2 years, with a clinical examination and blood sampling. SMRP was measured by an ELISA assay. Results: Median SMRP at the first visit was 0.45 [interquartile range (IQR) i.e. 25th-75th percentile: 0.30-0.67 nmol/l]. In all, 1,676 subjects (97.8%) were followed up for a median period of 47.1 months. SMRP was measured at the first visit and at both follow-up visits in 1,536 subjects. At follow-up, 3 subjects were diagnosed with an epithelioid mesothelioma. In these cases, SMRP at the first visit ranged from 0.17 to 0.52 nmol/l. Malignant pleural mesothelioma was diagnosed 9-17 months after the last SMRP evaluation. No SMRP variation was observed during the follow-up. Other 61 miscellaneous cancers were diagnosed (median SMRP at first visit: 0.50 nmol/l, IQR: 0.34-0.71 nmol/l). Conclusions: Our results did not support the usefulness of SMRP as an early marker for the detection of the disease for a time interval of 1 year.