Valentina Viggiani

HE4 combined with MDCT imaging is a good marker in the evaluation of disease extension in advanced epithelial ovarian carcinoma

The purpose of the study was to evaluate the expression of the biomarkers CA125 and HE4 combined with imaging, in patients with advanced epithelial ovarian cancer (EOC). Forty-six women with EOC were included in the study all affected with peritoneal carcinomatosis. Twenty-two of 46 patients (group I) had peritoneal carcinomatosis with small implants in single or in multiple sites (score 1); 24/46 patients (group II) had macro-nodular implants and omental thickening (score 2). High levels of CA125 (350 ± 11, mean ± SEM) have been observed in 21/22 patients of group I, and a similar value (370 ± 13) has been observed in all patients belonging to group II. HE4 positivity values (350 ± 9) have been observed in all group I patients, whereas all patients belonging to group II showed a higher value of HE4 (600 ± 12). Statistically significant differences were observed between the HE4 levels observed in group I patients in comparison with group II patients (p < 0.0001). In addition, we expressed the extension of lymph nodal disease in three scores: L1–L2–L3, and a statistically significant correlation was observed between high HE4 levels and severity of lymph nodal disease L3 (p < 0.0001). The availability of biomarkers, particularly HE4, together with sophisticated imaging techniques, strengthens the clinical relevance of this study, for the follow-up of patients with peritoneal carcinomatosis.

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients.

Abstract Objective: As a marker for Hepatocellular Carcinoma (HCC), Protein Induced by Vitamin K Absence II (PIVKA-II) seems to be superior to alpha fetoprotein (AFP). To better characterize the role of PIVKA-II, both AFP and PIVKA-II have been measured in Italian patients with diagnosis of HCC compared with patients affected by non-oncological liver pathologies. Materials and methods: Sixty serum samples from patients with HCC, 60 samples from patients with benign liver disease and 60 samples obtained from healthy blood donors were included in the study. PIVKA-II and AFP were measured by LUMIPULSE® G1200 (Fujirebio-Europe, Belgium). We considered as PIVKA-II cutoff 70 mAU/ml (mean +3SD) of the values observed in healthy subjects. Results: The evaluation of PIVKA-II showed a positivity of 70% in patients with HCC and 5% in patients with benign diseases (p < 0.0001) whereas high levels of AFP were observed in 55% of HCC patients and in 47% of patients with benign diseases. The combined Receiver Operating Characteristic (ROC) analysis of the two analytes revealed a higher sensitivity (75%) compared to those observed for the individual biomarkers. In conclusion, we demonstrate that as a marker for HCC, PIVKA-II is more specific for HCC and less prone to elevation during chronic liver diseases. Conclusions: The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice.

CLEIA CA125 evidences: good analytical performance avoiding “Hook effect”

Cancer antigen 125 (CA125) is a coelomic epithelium-related antigen carried by a high molecular weight glycoprotein complex. It is commonly used as a tumor marker for ovarian cancer to monitor disease progression and response to therapy and as an early detection for recurrence after treatment. The aim of this study was to test the reliability of two different assay methods, a radioimmunometric assay (RIA) and an automated chemiluminescent enzyme immunoassay (CLEIA) system, by measuring CA125 serum levels using both methods in 357 patients and comparing the results. Patients were recruited from Oncologic Unit A, Policlinico Umberto I, Roma. Eighty-six were healthy donors, while 271 were oncologic patients representing a variety of diagnoses. Within this group, 76 patients were diagnosed with an ovarian related pathology (28 cancerous and 48 benign). The evaluation of CA125 marker blood levels showed a high agreement in healthy donors group (R2 = 0.9003). Interesting results emerged when sera collected from oncologic patients were assessed: significant differences between the two assays were found in nine samples. When assayed again with RIA after a dilution, new values agreed with undiluted CLEIA values (R2 = 0.9847). Our data suggest an overall good comparison between the two methods. However, some artifacts were obtained with RIA and indicate an underlying presence of “hook effect”. CLEIA automated assay showed a good reliability and should be preferred to one-step radioimmunoassays in order to minimize errors.

HE4 and CA72.4 are Useful Biomarkers in the Follow-up of Epithelial Ovarian Cancer

The aim of this study was to investigate the role of serum biomarkers HE4 and CA72.4 at diagnosis and in the follow-up of patients with epithelial ovarian cancer (EOC).Seventy-eight patients with EOC were included and 40 of them were monitored during the follow-up. Serum levels of HE4 and CA72.4 were determined for all patients at diagnosis. Among these patients, the number of cases with an elevated level of each individual marker HE4 and CA72.4 was 85% and 72% respectively. A statistically significant difference was observed between the positivity of HE4 in comparison with Ca72.4 (p<0.02). In the follow-up period, we observed that tumor marker levels showed fluctuations during chemotherapy. As we combined the individual biomarkers, we observed increased values in 75% of the patients for HE4 with CA 72.4. In conclusion, our study has shown that the association of the biomarkers HE4 and CA72.4 provides a valuable contribution to the follow-up of EOC.