Microsatellite instability (MSI) is one of the hallmarks of colorectal cancer (CRC). Mismatch repair (MMR) protein expression may reflect MSI status. To analyze the concordance between MSI and MMR expression in CRC and their clinicopathological characteristics, 502 CRC patients were retrospectively collected in this study. Polymerase chain reaction-capillary electrophoresis (PCR-CE) was used to measure MSI, and MMR expression was determined by immunohistochemistry (IHC). The causes of non-concordance were analyzed. Chi-square test was used to find the correlation between MSI and various clinicopathological parameters. PCR-CE results showed 64 (12.7%) patients had high microsatellite instability (MSI-H); low microsatellite instability (MSI-L) and microsatellite stable (MSS) cases were 19 (3.8%)and 419 (83.5%), respectively. With regard to IHC, 430 (85.7%) showed proficient mismatch repair (pMMR) and 72 (14.3%) showed deficient mismatch repair (dMMR). The coincidence rate of MSI and MMR expression in CRC was 98.4% (494/502), with good concordance (Kappa = 0.932). Using PCR-CE as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of IHC were 100%, 98.2%, 88.9%, and 100%, respectively. MSI-H was more common in women, right colon, tumors ≥ 5 cm, ulcerative type, mucinous adenocarcinoma, poor differentiation, T stage I/II, and without lymph node or distant metastasis for CRC patients. In summary, MSI exhibited some typical clinicopathological characteristics. MSI and MMR expression in CRC had good concordance. However, it is still extremely necessary to perform PCR-CE. We recommend that testing packages of different sizes should be developed in clinical practice to create a testing echelon, to facilitate comprehensive selection according to experimental conditions, clinical diagnosis, and treatment needs.

Background: Primary squamous cell carcinoma (SCC) of the thyroid and anaplastic thyroid carcinoma (ATC) show significant clinical and histologic overlap. Their biological behaviors are so similar that the fifth WHO updates SCC as a morphologic pattern of ATC rather than a separate entity. However, molecular genomic evidence that determines them as the same histologic type is limited. We aimed to explore whether they belong to the same classification from a molecular-typing perspective. Methods: A cohort enrolled 15 SCCs and 15 ATCs was collected. Whole exome sequencing (WES) and RNA-sequencing were performed to analyze molecular genetic and gene-expression profiles. Results: Significantly differential-mutant genes were BRAF, DPCR1, PCYOX1L, BRSK2, NRG1, PRR14L, TET1, VAMP4 suggesting differences in mutation level, as well as differences in high-frequency mutated genes, and SCC had a much lower tumor mutation burden than ATC. Mutational co-occurrence and mutual exclusion were less frequent in SCC than in ATC. 2047 differential-express genes were screened, indicating differences in gene expression were extremely strong. In principal component analysis, ATC and SCC could be notably clustered together, respectively, meanwhile they could be explicitly distinguished. Unsupervised clustering analysis validated they can indeed be clearly separated from each other which demonstrated that they may be two distinctive entities. Conclusions: It is controversial yet SCC is classified as a morphologic pattern of ATC. We revealed that SCC exhibited molecular genetic characteristics distinct from ATC. Although the fifth WHO categorizes them together, this study may provide strong molecular genetic evidence for the next edition of WHO classification that may allow for the separation of thyroid SCC from ATC.