Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features.

BACKGROUND: Differences exist between the proximal and distal colon in terms of developmental origin, exposure to patterning genes, environmental mutagens, and gut flora. Little is known on how these differences may affect mechanisms of tumorigenesis, side-specific therapy response or prognosis. We explored systematic differences in pathway activation and their clinical implications. MATERIALS AND METHODS: Detailed clinicopathological data for 3045 colon carcinoma patients enrolled in the PETACC3 adjuvant chemotherapy trial were available for analysis. A subset of 1404 samples had molecular data, including gene expression and DNA copy number profiles for 589 and 199 samples, respectively. In addition, 413 colon adenocarcinoma from TCGA collection were also analyzed. Tumor side-effect on anti-epidermal growth factor receptor (EGFR) therapy was assessed in a cohort of 325 metastatic patients. Outcome variables considered were relapse-free survival and survival after relapse (SAR). RESULTS: Proximal carcinomas were more often mucinous, microsatellite instable (MSI)-high, mutated in key tumorigenic pathways, expressed a B-Raf proto-oncogene, serine/threonine kinase (BRAF)-like and a serrated pathway signature, regardless of histological type. Distal carcinomas were more often chromosome instable and EGFR or human epidermal growth factor receptor 2 (HER2) amplified, and more frequently overexpressed epiregulin. While risk of relapse was not different per side, SAR was much poorer for proximal than for distal stage III carcinomas in a multivariable model including BRAF mutation status [N = 285; HR 1.95, 95% CI (1.6-2.4), P < 0.001]. Only patients with metastases from a distal carcinoma responded to anti-EGFR therapy, in line with the predictions of our pathway enrichment analysis. CONCLUSIONS: Colorectal carcinoma side is associated with differences in key molecular features, some immediately druggable, with important prognostic effects which are maintained in metastatic lesions. Although within side significant molecular heterogeneity remains, our findings justify stratification of patients by side for retrospective and prospective analyses of drug efficacy and prognosis.

Mars water-ice clouds and precipitation.

The light detection and ranging instrument on the Phoenix mission observed water-ice clouds in the atmosphere of Mars that were similar to cirrus clouds on Earth. Fall streaks in the cloud structure traced the precipitation of ice crystals toward the ground. Measurements of atmospheric dust indicated that the planetary boundary layer (PBL) on Mars was well mixed, up to heights of around 4 kilometers, by the summer daytime turbulence and convection. The water-ice clouds were detected at the top of the PBL and near the ground each night in late summer after the air temperature started decreasing. The interpretation is that water vapor mixed upward by daytime turbulence and convection forms ice crystal clouds at night that precipitate back toward the surface.

Histopathology of the experimental tick-borne encephalitis in mice.

This paper is concerned with the histopathology of the tick-borne encephalitis virus experimental infection in mice. The lesions observed in the kidneys, spleen, myocardium and especially in the encephalon are characteristic of severe vasculitis which could be the first and probably the most important event in the virus-induced encephalitis.

Isolation of Bhanja virus in Romania.

The presence of Bhanja virus was notified for the first time in our country in 1986, by the serological study performed on human and domestic animals sera. In 1988 four Bhanja virus strains from Dermacentor ticks were isolated in Alba and Caras-Severin counties. A high percent of domestic animals, originating in this region, presents antibodies to the isolated strains and also to Bhanja virus reference strain.