Cell Cycle Proteins Predict Recurrence in Stage II and III Colon Cancer

Purpose

To investigate the prognostic value of multiple cell cycle-associated proteins in a large series of stage II and III colon cancers.

Methods

From formalin-fixed, paraffin-embedded tumor samples of 386 patients with stage II and III colon cancer, DNA was isolated and tissue microarrays were constructed. Tissue microarray slides were immunohistochemically stained for p21, p27, p53, epidermal growth factor receptor, Her2/Neu, β-catenin, cyclin D1, Ki-67, thymidylate synthase, and Aurora kinase A (AURKA). Polymerase chain reaction–based microsatellite instability analysis was performed to allow for stratification of protein expression by microsatellite instability status.

Results

Overall, low p21, high p53, low cyclin D1, and high AURKA expression were significantly associated with recurrence (P = 0.01, P < 0.01, P = 0.04, and P < 0.01, respectively). In stage II patients who did not receive adjuvant chemotherapy (n = 190), significantly more recurrences were observed in case of low-p21 and high-p53-expressing tumors (P < 0.01 and P = 0.03, respectively). In stage III patients who did not receive chemotherapy, high p53 expression was associated with recurrence (P = 0.02), and in patients who received chemotherapy, high AURKA expression was associated with relapse (P < 0.01). In patients with microsatellite stable tumors, high levels of p53 and AURKA were associated with recurrence (P = 0.01 and P < 0.01, respectively). Multivariate analysis showed p21 (odds ratio 1.6, 95% confidence interval 0.9–2.8) and AURKA (odds ratio 2.7, 95% confidence interval 1.3–5.6) to be independently associated with disease recurrence.

Conclusions

p21, p53, cyclin D1, and AURKA could possibly be used as prognostic markers to identify colon cancer patients with high risk of disease recurrence.

     

Optimal timing for prediction of pathologic complete response to neoadjuvant chemoradiotherapy with diffusion-weighted MRI in patients with esophageal cancer

European Radiology - This study was conducted in order to determine the optimal timing of diffusion-weighted magnetic resonance imaging (DW-MRI) for prediction of pathologic complete response (pCR)...     

Recommendations for whole genome sequencing in diagnostics for rare diseases

In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) and insertions/deletions (indels)). Since then, Whole Genome Sequencing (WGS) has been increasingly introduced in the diagnosis of rare diseases as WGS allows the simultaneous detection of SNVs, Structural Variants (SVs) and other types of variants such as repeat expansions. The use of WGS in diagnostics warrants the re-evaluation and update of previously published guidelines. This work was jointly initiated by EuroGentest and the Horizon2020 project Solve-RD. Statements from the 2016 guidelines have been reviewed in the context of WGS and updated where necessary. The aim of these recommendations is primarily to list the points to consider for clinical (laboratory) geneticists, bioinformaticians, and (non-)geneticists, to provide technical advice, aid clinical decision-making and the reporting of the results.Subject terms: Next-generation sequencing, Medical genetics     

The morphologic effect of short-term medical therapy of endometriosis

A clinicopathologic study of a short-term medical treatment of endometriosis with danazol or gestrinone was performed in 50 patients with endometriosis and infertility. The cellular response to the therapy was evaluated and graded according to morphologic, that is, histologic and ultrastructural, criteria. A 2-month therapy with 1.25 mg of gestrinone daily induced a degree of cellular inactivation and degeneration of the endometriotic implants that was more pronounced than after 4 months of therapy with either gestrinone (2.5 mg twice or thrice weekly) or danazol (600 mg daily). There was no correlation between the morphologic response to treatment and either the hormonal response of the foci during the menstrual cycle before therapy or the change in laparoscopic staging of endometriosis at the end of therapy. It is suggested that a short-term medical treatment should be further evaluated clinically in the treatment of endometriosis and infertility.     

Ovum transport after microsurgical anastomosis of the rabbit oviduct

From experimental work in rabbits it is known that pregnancy outcome is influenced unfavorably by tubal resection anastomosis in spite of the preservation of tubal patency. In 104 Dutch belted rabbits the impact of microsurgical resection anastomoses on ovum transport during the first 24 hours after ovulation was examined. In oviducts in which the ampulla had been operated on, ovum transport was delayed. Mucosal irregularities that interfere with normal ampullary transport by cilia activity may account for the delay noted. Alterations in the duration of ovum transport in the oviduct may influence pregnancy outcome by creating an inappropriate tubal environment for the early embryo or by creating asynchrony between the embryo and the endometrium. No changes were observed in transport in oviducts in which the isthmus had been operated on: even a small segment of isthmus seems to act as a physiologic sphincter and to prevent premature ovum entrance into the uterus.