Microsatellite instability in hepatocellular carcinoma in non‐cirrhotic liver in patients older than 60 years

Abstract

Our study showed that MSI is not implicated in the pathogenesis of a subset of HCC affecting elderly patients without chronic liver disease. Further studies are needed to clarify the pathogenesis of HCC in this particular setting.

Hepatocellular carcinoma as extracolonic manifestation of Lynch syndrome indicatesSEC63as potential target gene in hepatocarcinogenesis

“…However, data on the frequency of sporadic MSI in HCC are controversial [10][11][12][13][14]. Hepatocarcinogenesis is a heterogeneous process [15], mostly occurring on a background of inflammation and fibrosis caused by chronic liver disease.…”

The liver: another organ involved in Muir Torre syndrome?

“…Other studies supported this finding, showing that hepatocellular carcinogenesis was neither related to microsatellite instability nor to MSH1 and MSH2 mutations, either in patients with cirrhosis-related HCC [19,20], or in patients with HCC but without cirrhosis. [21]. MTS, a clinical variant of HNPCC syndrome, has rarely been associated with hepato-biliary tract malignancy.…”

Low Levels of Microsatellite Instability at Simple Repeated Sequences Commonly Occur in Human Hepatocellular Carcinoma

“…Previously published studies that addressed this question varied tremendously in terms of HCC etiology, a characteristic that depends largely on the geographical origin of the patients, and in the number of tumors analyzed that was between 8 and 56 (5,6,(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)39). Furthermore, the type and number of markers also varied considerably from a single mononucleotide repeat marker (14) to 55 microsatellite markers, mostly dinucleotide repeated sequences (19); few studies also included trinucleotide, tetranucleotide and hexanucleotide repeats whose genetic stability may involve DNA repair pathways other than MMR (6,9,16).…”

“…Several reasons may contribute to the variability observed in the data published: (i) analyses of MSI profiles using highly polymorphic markers other than mononucleotide repeats are somehow tricky to interpret outside of well-trained laboratories and may lead to misinterpretation, (ii) the number of samples analyzed was often too limited to definitely establish the percentage of MSI, (iii) underlying etiology differed widely among studies. Lastly, the only study performed using the recently developed highly efficient mononucleotide pentaplex PCR system investigated no more than eight cases of HCC; besides these tumors all occurred in elderly patients with no chronic liver disease (20). Based on our expertise in analyzing microsatellite profiles (41-47), we investigated MSI in a large collection of HCC of various etiologies using robust and accurate PCR-based MSI testing techniques, both at mononucleotide repeats, using the goldstandard pentaplex PCR based on five nearly monomorphic mononucleotide markers, and at 13 dinucleotide repeats located on 8 different chromosomes.…”

“…Analysis of MMR protein expression by immunohistochemistry (IHC) is also very popular, with MSH2 and MLH1 being performed in routine while MSH6 and PMS2 are analyzed in rare studies. In HCC, MSI has been investigated by IHC (14,18,20), and by PCR using highly variable sets of microsatellite loci (5, 6, 9-11, 13-20, 39) ( Table I). …”