Nectin-4 is a new histological and serological tumor associated marker for breast cancer.

INTRODUCTION: Breast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research.Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma. METHODS: Expression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC), respectively. mRNA expression was measured by quantitative PCR. Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC) at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test. RESULTS: Nectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels correlate with the number of metastases (P = 0.038). Serum Nectin-4 is also a marker of therapeutic efficiency and correlates, in 90% of cases, with clinical evolution. CONCLUSION: Nectin-4 is a new tumor-associated antigen for breast carcinoma. Nectin-4 is a new bio-marker whose use could help refine breast cancer taxonomy and improve patients' follow-up. Nectin-4 emerges as a potential target for breast cancer immunotherapy.

Serum levels of Hemorphin-7 peptides in patients with breast cancer.

BACKGROUND: Increased expression of cathepsin D (CD) and B (CB) is found in some cancers and correlates with the development of clinical metastases. It was suggested that these cathepsins could be used as prognostic markers, especially CD in breast cancer. Because serum level of Hemorphin-7 (H7) peptides could reflect CD activity, we have hypothesised that it could be used as a prognostic factor in breast cancer. METHODS: To verify this hypothesis, H7 serum levels from 62 breast cancer patients and 25 healthy controls were measured by ELISA. RESULTS: The mean serum concentration of H7 was 2.27+/-0.63 mumol/l in breast cancer patients in comparison with 4.09+/-1.05 mumol/l in controls (p=0.002). This reduced level of H7 in breast cancer could be due to the over-expression of CB, which exhibits strong interaction with H7 in vitro, with a ratio K(cat)/K(m) estimated at 18000 s(-1) M(-1). CONCLUSIONS: Because H7 serum levels did not correlate with other parameters including age, CA15-3 and ACE markers, it seems that they might be used as independent markers for the diagnosis of breast cancer.

Value of (99m)Tc-ECD SPET for the diagnosis of dementia with Lewy bodies.

Despite improved diagnostic accuracy, differentiation of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) on the basis of clinical findings remains problematic. The purpose of this retrospective study was to evaluate the utility of technetium-99m ethyl cysteinate dimer (ECD) single-photon emission tomography (SPET) as a potential tool for the diagnosis of DLB and discrimination from AD. Cerebral perfusion patterns detected by (99m)Tc-ECD SPET were compared in patients presenting with a probable diagnosis of DLB ( n=34) or AD ( n=28). Tracer distribution was quantified using the region of interest technique in eight symmetrical paired zones and expressed as a perfusion index (ratio of mean uptake in a brain region to that in the cerebellum). Comparison of findings in the DLB and AD groups demonstrated significant differences in mean perfusion indexes in the right occipital region ( P=0.004), left occipital region ( P=0.005) and left medial temporal region ( P=0.013). Mean perfusion indexes in the right and left occipital regions were lower in DLB than in AD patients. Conversely, the mean perfusion index in the left medial temporal region was lower in AD than in DLB patients. DLB was correctly identified in 22 patients (sensitivity, 65%) while AD was correctly identified in 20 patients (specificity, 71%). In the DLB group, right and left occipital perfusion indexes were 0.95 or more in all eight non-hallucinating patients, and bilateral occipital hypoperfusion was observed in 15 of the 26 patients with visual hallucinations (57.7%). To our knowledge, this is the first study in which (99m)Tc-ECD SPET has been used exclusively for the diagnosis of DLB. The results suggest that brain perfusion scintigraphy could be helpful in distinguishing DLB from AD if diagnosis based on clinical criteria alone is difficult. The findings also support a link between visual hallucinations and structural/functional changes in the occipital region in DLB patients.