MSIHMedical School for International Health (US and Israel)
MSIHMissing Surface Inflection Hypothesis (second language learning)
MSIHMaster of Science in Industrial Hygiene (degree; various locations)
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Although patients with tumors showing high IS (IS-High) are overrepresented in the MSIH group, compared with the MSS group, there is a substantial number of IS-High cases in the MSS group, indicating that there is a good number of MSS cases that are immunogenic.
Tumors showing instability at two or more of these repeats (40% of markers) are defined at high instability (MSIH); those with instability between 20-40% are classified as low instability (MSI-L) [26]; tumors without alteration (20% or less) are classified as stable (MSS).
Those patients are defined as MSI-like and share the hypermutated status as pure MSIH patients.
The coding regions of genes usually only harbor short repeat sequences, such as the 10-A and 8-G repeats in TGFBR2 and BAX genes, respectively, that are frequently mutated in MSIH human tumors [17].
An association between MSI-H CRCs and female sex has been recognized but the association is valid only when MSIH CRCs are sporadic.
Additionally, MSIH colon cancers did not differ from non-MSI-H colon cancers with wild-type KRAS and BRAF in terms of disease-free survival.
Despite the small size of these studies, the FDA has approved pembrolizumab and nivolumab for use in MSIH mCRC that has progressed on chemotherapy.
(9) The SSA/Ps can give rise to both microsatellite unstable (MSIH) or MSS cancers (Figure 1).
(75) Specifically, mutations in PIK3CA exon 20 and PTEN have been shown to significantly associate with the sessile-serrated pathway including MSIH, CIMP-high, and BRAF mutations, whereas PIK3CA exon 9 mutations are overrepresented in MSS/CIMP-low/KRAS mutant cancers.
(37,78) O'Brien et al (6) showed that the molecular features of carcinomas arising from serrated lesions overlapped, in a study wherein the residual serrated adenoma was compared with the adjacent invasive adenocarcinoma ("serrated carcinoma"), with some cases in which both the serrated adenoma and the adenocarcinoma were MSIH with matching loss of MLH1 by immunohistochemistry and other cases with a pattern of negative microsatellite instability in both the cancer and serrated polyp.
The majority of SSA/Ps with foci of dysplasia will show loss of expression of MLH1, indicating development of MSIH. In our practice we stain for PMS2 in parallel, because there is concomitant loss of PMS2 in true loss of expression of MLH1.
As shown in Table 1, 10 (43.5%), 4 (17.4%) and 4 (17.4%) of the 23 MSIH endometrial carcinomas had the presence of a 1-, 2-, or 3-base deletion mutation within this element, resulting in an A12, A11, or A10 repeats, respectively.