Correlations of differentially expressed gap junction connexins cx26, cx30, cx32, cx43 and cx46 with breast cancer progression and prognosis.

BACKGROUND AND AIMS: Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers. MATERIALS AND METHODS: Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally representing all tumor grades, using immunofluorescence and multilayer, multichannel digital microscopy. Prognostic correlations were plotted in Kaplan-Meier curves and tested using the log-rank test and cox-regression analysis in univariate and multivariate models. RESULTS: The expression of GJA1/Cx43, GJA3/Cx46 and GJB2/Cx26 and, for the first time, GJA6/Cx30 and GJB1/Cx32 was revealed both in normal human mammary glands and breast carcinomas. Within their subfamilies these connexins can form homo- and heterocellular epithelial channels. In cancer, the array datasets cross-validated each other's prognostic results. In line with the significant correlations found at mRNA level, elevated Cx43 protein levels were linked with significantly improved breast cancer outcome, offering Cx43 protein detection as an independent prognostic marker stronger than vascular invasion or necrosis. As a contrary, elevated Cx30 mRNA and protein levels were associated with a reduced disease outcome offering Cx30 protein detection as an independent prognostic marker outperforming mitotic index and necrosis. Elevated versus low Cx43 protein levels allowed the stratification of grade 2 tumors into good and poor relapse free survival subgroups, respectively. Also, elevated versus low Cx30 levels stratified grade 3 patients into poor and good overall survival subgroups, respectively. CONCLUSION: Differential expression of Cx43 and Cx30 may serve as potential positive and negative prognostic markers, respectively, for a clinically relevant stratification of breast cancers

Infrared tympanic thermography as a substitute for a probe in the evaluation of ear temperature for post-mortem interval determination: a pilot study

Reported methods which have been used to measure tympanic temperatures on cadavers up to now are quite invasive. They involve the use of a probe which can perforate the tympanic membrane and frequently causes bleeding from the ear. For this reason a non traumatic method for estimating tympanic temperature should be applied. Infrared tympanic thermometry seems to be a plausible option. Reliability of infrared tympanic thermometry (ITT) has been largely assessed on living individuals but only one author up to now has assessed its applicability for post-mortem interval determination. Thus the authors set out to test the difference between ear temperatures taken with a probe vs. ITT, differences between left and right ear and reproducibility of measurements of ITT. The aim of the study was to verify whether ITT could be a plausible option for measuring ear temperature for PMI estimation. Ear temperatures were taken on 25 cadavers (15 males, 10 females). Temperatures were taken alternately by similarly trained personnel by two technical methods (Checktemp 1 thermocouple probe and First Temp Genius infrared thermometer) for a total of 93 measurements. Statistical analysis of the data was performed using SAS statistical software. The range of temperature measured was from 20 to 28 degrees C, statistical analysis revealed no differences within the two technical methods, both for right and left ear (ITT: 22.33+/-0.35 vs. probe: 23.08+/-0.25; P=0.087). The study shows the ITT method can be considered as a possible alternative to the probe for measuring ear temperative and further studies should be considered