Elevated circulating chromogranin A (CgA) levels are found in neuroendocrine tumors (NETs), but the diagnostic usefulness of this marker is still debatable. To assess the role of CgA for the diagnosis of gastroenteropancreatic (GEP) NETs and the identification of metastatic patients, an Italian multicenter observational study has been performed. CgA was evaluated in 202 GEP NET patients by IRMA and ELISA. The cutoffs for diagnosis and presence of metastases were identified by receiver-operating characteristic (ROC) curve. We found good correlation between IRMA and ELISA. The ROC analysis identified a cutoff of 53 ng/ml for IRMA and 16 U/l for ELISA as discriminating between controls and patients with active disease (sensitivity 71.3 and 84%; specificity 71 and 85% respectively). Metastases were present in 123 patients, having significantly higher CgA levels than patients without metastases. ROC analysis identified a cutoff of 146 ng/ml for IRMA and 67.3 U/l for ELISA as discriminating between patients with and without metastases (sensitivity 57 and 63.3%; specificity 55.6 and 71.4% respectively). For pancreatic NETs positive and negative predictive values were 84 and 78% respectively (90% specificity and 68% sensitivity). We found lower CgA levels in patients with extensive metastatic spread than in those with liver metastases only. These data assess the role of CgA evaluation in GEP NETs, and demonstrate that higher CgA levels associate with metastatic disease, confirming that CgA levels can provide a helpful practical biochemical marker for the clinical management of NETs, but with low sensitivity and specificity.

A pilot newborn screening program for 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) was conducted in Alaska using a 3-mm disc filter paper elution technique of capillary whole blood for 17-hydroxyprogesterone (17-OHP) by RIA. The filter paper specimens were provided via the mandated newborn screening program. The highest values of 17-OHP in a control population of 4569 consecutive normal neonates, aged 2–14 days, was 40 pg/disc, and the range of values for 20 newborns with proven CAH was 57–980 pg/disc. All Alaskan newborns with 17-OHP levels of 57 pg/disc or greater were referred for diagnostic workup, and initially, those with 17-OHP levels of 41–56 pg/disc were recalled for a second specimen. However, the range for recall was changed subsequently to the 17-OHP level greater than 51 pg/disc, since no newborns with 17-OHP level below 50 pg/disc were found to be affected in the initial screening. In a 30-month period, the Alaskan newborns screened on the third day of life consisted of a total of 19,677 consecutive births (13,733 Caucasians, 1,131 Yupik Eskimos, 3,173 other natives, and 1,640 others). Sixteen had 17-OHP values greater than 57 pg/disc, of which 4 (3 Yupik Eskimos and 1 Caucasian) were proven to have the salt-losing form of CAH. Of the remaining 12, 4 were not available for follow-up; 8 were distressed premature infants, including 2 infants who died with severe prematurity. In addition, 1 Yupik Eskimo newborn who was clinically suspected and treated for CAH at birth before confirmation of the diagnosis, was subsequently confirmed to have CAH by filter paper 17-OHP determination off treatment. Of the 14 newborns whose 17-OHP values were 51–56 pg/disc, 13 were recalled and proven to be normal, and 1 could not be located. Thus, the neonatal Alaskan screening, including 1 newborn who was clinically suspected for CAH, revealed 4 infants with the salt-losing form of CAH in 1,131 live births in Yupik Eskimos and 1 infant with the salt-losing form of CAH in 13,733 Caucasian live births. These data indicate a prevalence of this disorder of 1 in 282 in Yupik Eskimo live births and 1 in 13,733 in Caucasian live births. The false positive and recall rates were 0.05% and 0.1%, respectively. The present study demonstrates the feasibility of a newborn screening program for CAH and indicates that the frequency of the salt-losing form of CAH may be greater than previously reported by the case assessment method in Yupik Eskimos in Alaska.

Activated leukocyte cell adhesion molecule (ALCAM) has been implicated in tumorigenesis. Our goal was to examine the levels of ALCAM, in addition to the classical breast cancer tumor markers carbohydrate antigen 15‐3 (CA15‐3) and carcinoembryonic antigen (CEA), in serum by quantitative enzyme‐linked immunosorbent assay for diagnosis in breast cancer patients. The 3 proteins were measured in serum of 100 healthy women, 50 healthy men and 150 breast carcinoma patients. The diagnostic sensitivity and specificity of the tests were calculated and the association of serum marker concentrations with various clinicopathologic variables was examined using nonparametric Kruskal‐Wallis tests. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the biomarkers. ALCAM, with area under the curve (AUC) of 0.78 [95% CI: 0.73, 0.84] outperformed CA15‐3 (AUC = 0.70 [95% CI: 0.64, 0.76]) and CEA (AUC= 0.63 [95% CI: 0.56, 0.70]). The incremental values of AUC for ALCAM over that for CA15‐3 were statistically significant (Delong test, p < 0.05). Combining CA15‐3 and ALCAM yielded a ROC curve with an AUC of 0.81 (95% CI [0.75, 0.87]). Serum ALCAM appears to be a new biomarker for breast cancer and may have value for disease diagnosis. © 2009 UICC

DSCAM-AS1 is a cancer-related long noncoding RNA with higher expression levels in Luminal A, B, and HER2-positive Breast Carcinoma (BC), where its expression is strongly dependent on Estrogen Receptor Alpha (ERα). DSCAM-AS1 expression is analyzed in 30 public datasets and, additionally, by qRT-PCR in tumors from 93 BC patients, to uncover correlations with clinical data. Moreover, the effect of DSCAM-AS1 knockdown on gene expression and alternative splicing is studied by RNA-Seq in MCF-7 cells. We confirm DSCAM-AS1 overexpression in high grade Luminal A, B, and HER2+ BCs and find a significant correlation with disease relapse. In total, 908 genes are regulated by DSCAM-AS1-silencing, primarily involved in the cell cycle and inflammatory response. Noteworthily, the analysis of alternative splicing and isoform regulation reveals 2085 splicing events regulated by DSCAM-AS1, enriched in alternative polyadenylation sites, 3′UTR (untranslated region) shortening and exon skipping events. Finally, the DSCAM-AS1-interacting splicing factor heterogeneous nuclear ribonucleoprotein L (hnRNPL) is predicted as the most enriched RBP for exon skipping and 3′UTR events. The relevance of DSCAM-AS1 overexpression in BC is confirmed by clinical data and further enhanced by its possible involvement in the regulation of RNA processing, which is emerging as one of the most important dysfunctions in cancer.