Gene expression profiling reveals GC and CEACAM1 as new tools in the diagnosis of lung carcinoids.

BACKGROUND: Classification of lung carcinoids into typical and atypical is a diagnostic challenge since no immunohistochemical tools are available to support pathologists in distinguishing between the two subtypes. A differential diagnosis is essential for clinicians to correctly discuss therapy, prognosis and follow-up with patients. Indeed, the distinction between the two typical and atypical subtypes on biopsies/cytological specimens is still unfeasible and sometimes limited also after radical surgeries. By comparing the gene expression profile of typical (TC) and atypical carcinoids (AC), we intended to find genes specifically expressed in one of the two subtypes that could be used as diagnostic markers. METHODS: Expression profiling, with Affymetrix arrays, was performed on six typical and seven atypical samples. Data were validated on an independent cohort of 29 tumours, by means of quantitative PCR and immunohistochemistry (IHC). RESULTS: High-throughput gene expression profiling was successfully used to identify a gene signature specific for atypical lung carcinoids. Among the 273 upregulated genes in the atypical vs typical subtype, GC (vitamin D-binding protein) and CEACAM1 (carcinoembryonic antigen family member) emerged as potent diagnostic markers. Quantitative PCR and IHC on a validation set of 17 ACs and 12 TCs confirmed their reproducibility and feasibility. CONCLUSIONS: GC and CEACAM1 can distinguish between TC and AC, defining an IHC assay potentially useful for routine cytological and histochemical diagnostic procedures. The high sensitivity and reproducibility of this new diagnostic algorithm strongly support a further validation on a wider sample size.

Predicting haemorrhage in pre-hospital traumatic patients: evaluation of the novel heart-to-arm time index.

BACKGROUND: Early recognition of hypovolaemia in trauma patients is very important. However, the most often used clinical signs, such as hypotension and tachycardia, lack specificity and sensitivity. METHODS: We propose a non-invasive index of hypovolaemia, the heart to arm time (iHAT), based on a modified pulse transit time indexed to heart rate. Pulse transit time is the sum of pre-ejection period and vascular transit time. Following pre-load reductions due to hypovolaemia, ventricular diastolic filling time increases causing an increase in pre-ejection-period, pulse transit time, and hence iHAT. One hundred and four consecutive patients with suspected major trauma were enrolled. The primary aim was to evaluate the use of the iHAT for detecting haemorrhage in major trauma. The secondary end point was to compare the specificity and sensitivity of iHAT compared to commonly used indexes. RESULTS: iHAT was calculated in 84 subjects, 11 of whom were haemorrhagic. iHAT discriminated haemorrhagic from non-haemorrhagic group (46.8% vs. 66.9%, P < 0.0001). The cut-off for iHAT with the best compromise between sensitivity (90.9%) and specificity (100%) was reached at the 58.78% level. Comparing haemorrhagic and non-haemorrhagic patients, the area under the ROC curve was 0.952 for iHAT, 0.835 for heart rate, and 0.911 for systolic blood pressure, showing no significant differences. CONCLUSIONS: iHAT is a non-invasive index that can identify haemorrhage in trauma patients with high sensitivity and specificity. These data should be considered as an exploration, but any conclusion should be validated in a new set of consecutive patients.

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA).

BACKGROUND: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. METHODS: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. RESULTS: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P = 0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P = 0.5) mutation carriers. CONCLUSION: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.