Colorectal Tumour Microsatellite Instability Test Results: Perspectives from Patients

<p>Abstract</p> <p>Purpose</p> <p>To determine which individuals with colorectal cancer (CRC) were interested in knowing the results of their tumour microsatellite instability (MSI) and immunohistochemistry (IHC) testing. We were also interested in the patients' reasons for choosing to learn their results and in the impact of those results on overall self-assessed quality of life.</p> <p>Patients and Methods</p> <p>CRCs from 414 individuals were assayed for MSI and IHC for DNA mismatch repair gene products (<it>MLH1</it>, <it>MSH2</it>, <it>MSH6</it>). Individuals were invited to learn their MSI/IHC results. They randomly received either brief or extended educational materials about the testing and a pretest survey to learn reasons for their interest and to assess their pretest quality of life.</p> <p>Results</p> <p>Of the 414 individuals, 307 (74%) chose to learn their results. There was no significant difference in interest in knowing test results according to gender, age, educational level, or family history of colon cancer. The level of detail in the information piece received by the patients did not influence their desire to know their test results. Self-assessed quality of life was not altered by receiving results and was not correlated with the test outcome.</p> <p>Conclusions</p> <p>Individuals with colorectal cancer had a high level of interest in learning their individual MSI/IHC test results and did not seem deterred by the inherent complexity or ambiguity of this information. Regardless of test outcome, results did not significantly affect self-assessed quality of life. Further studies are needed to assess comprehension of results and behavioural changes resulting from the learning of MSI/IHC results.</p

2D-NMR reveals different populations of exposed lysine residues in the apoB-100 protein of electronegative and electropositive fractions of LDL particles[S]

Several potentially atherogenic LDL subfractions present low affinity for the LDL receptor, which result in impaired plasma clearance. Electronegative LDL [LDL(−)] is one of these minor subfractions and the molecular basis for its reduced receptor affinity is not well understood. In the present study, high-resolution 2D-NMR spectroscopy has been employed to characterize the surface-exposed lysine residues of the apolipoprotein (apo)B-100 protein in both LDL(−) and LDL(+) subfractions. LDL(+) showed two populations of lysine residues, similar to those previously described in total LDL. “Normal” Lys have a pka of 10.4 whereas “active” Lys have a pka of 8.8 and have been suggested to be involved in receptor binding. In contrast to LDL(+), the LDL(−) subfraction presented a third type of Lys, named as “intermediate” Lys, with a different microenvironment and higher basicity (pka 10.7). These intermediate Lys cannot be reliably identified by 1D-NMR. Because the abundance of normal Lys is similar in LDL(+) and LDL(−), the intermediate Lys in the apoB-100 molcule of LDL(−) should come from a group of active Lys in LDL(+) particles that have a less basic microenvironment in the LDL(−) particle. These differences between LDL(+) and LDL(−) are indicative of a distinct conformation of apoB-100 that could be related to loss of affinity of LDL(−) for the LDL receptor