Venous invasion detectable only by elastic stain shows weak prognostic value in colon cancer.

AIMS: Large venous invasion (VI) is prognostically significant in colon cancer. The increased use of elastic stains by pathologists results in higher VI detection rates compared to routine stains alone. This study assesses the prognostic value of VI detected by elastic versus routine stains. METHODS AND RESULTS: Colon cancers resected between 2014 and 2017 underwent pathology slide review for VI. Cases without VI on routine stain were stained by elastic trichrome and re-examined. Demographic, clinical, pathological and outcome data were gathered by retrospective review. Kaplan-Meier curves with log-rank tests were performed for survival categorised by VI status. Cox regression was performed for multivariate analysis. Of 277 cases, 97 (35%) showed VI by routine stain alone, with an additional 58 (21%) discovered by subsequent elastic stains. Thus, elastic trichrome increased VI detection by 60%. However, only VI detected by routine stain showed worse overall survival (P < 0.001). VI detected by elastic stain only was not prognostically different from cases without VI (P = 0.428). For stage 2 cancers, VI was not prognostically significant regardless of method of detection. For stage 3 cases, only VI detected by routine stain was prognostic for overall survival (P = 0.002) with a hazard ratio of 4.04 by multivariate regression (P = 0.028). CONCLUSIONS: VI detectable only by elastic stains do not show prognostic significance for survival in colon cancer. For pathologists with high baseline VI detections rates on routine stain, reflexive use of elastic stain may be of limited value.

Quantitative Immunoblotting of Cell Lines as a Standard to Validate Immunofluorescence for Quantifying Biomarker Proteins in Routine Tissue Samples.

Quantification of proteins of interest in formalin-fixed, paraffin-embedded (FFPE) tissue samples is important in clinical and research applications. An optimal method of quantification is accurate, has a broad linear dynamic range and maintains the structural integrity of the sample to allow for identification of individual cell types. Current methods such as immunohistochemistry (IHC), mass spectrometry, and immunoblotting each fail to meet these stipulations due to their categorical nature or need to homogenize the sample. As an alternative method, we propose the use of immunofluorescence (IF) and image analysis to determine the relative abundance of a protein of interest in FFPE tissues. Herein we demonstrate that this method is easily optimized, yields a wide dynamic range, and is linearly quantifiable as compared to the gold standard of quantitative immunoblotting. Furthermore, this method permits the maintenance of the structural integrity of the sample and allows for the distinction of various cell types, which may be crucial in diagnostic applications. Overall, this is a robust method for the relative quantification of proteins in FFPE samples and can be easily adapted to suit clinical or research needs.

Short-chain aliphatic polysulfonates inhibit the entry of Plasmodium into red blood cells.

Several steps in the pathogenesis of a Plasmodium falciparum infection depend on interactions of parasite surface proteins with negatively charged sugars on the surface of host cells such as sialate residues or glycosaminoglycans. For these reasons, our previous studies examining agents that interfere with heparan sulfate-protein binding during amyloidogenesis suggested that short-chain aliphatic polysulfonates may prove useful as antimalarial agents. A series of related polysulfonates were synthesized and assessed both in tissue culture with the asexual stages of P. falciparum in human red blood cells and in vivo by use of Plasmodium berghei infections in mice. Poly(vinylsulfonate sodium salt) (molecular weight range, 1,500 to 3,000) proved effective in interfering with P. falciparum merozoite entry into human red blood cells and significantly delaying the increase in the level of P. berghei parasitemia in mice. The concept that anionic molecules that mimic large polysaccharide structures may have antimalarial properties has been suggested and examined previously. Our results suggest that related anionic agents [poly(vinylsulfonate sodium salt)-like molecules] orders of magnitude smaller than those previously considered may prove useful in abrogating merozoite entry into erythrocytes and may potentially block sporozoite entry into liver cells. Structure-activity studies conducted to enhance these properties may provide compounds with scope for significant further analysis and development.