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Cited by 313

The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index.

The evolving role of microsatellite instability in colorectal cancer: A review

Open access
Gelsomino, Fabio, Barbolini, Monica, Spallanzani, Andrea, Pugliese, Giuseppe, Cascinu, Stefano·2016·Cancer Treatment Reviews
DOI 10.1016/j.ctrv.2016.10.005
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Abstract

Microsatellite instability (MSI) is a molecular marker of a deficient mismatch repair (MMR) system and occurs in approximately 15% of colorectal cancers (CRCs), more frequently in early than late-stage of disease. While in sporadic cases (about two-thirds of MSI-H CRCs) MMR deficiency is caused by an epigenetic inactivation of MLH1 gene, the remainder are associated with Lynch syndrome, that is linked to a germ-line mutation of one of the MMR genes (MLH1, MSH2, MSH6, PMS2). MSI-H colorectal cancers have distinct clinical and pathological features such as proximal location, early-stage (predominantly stage II), poor differentiation, mucinous histology and association with BRAF mutations. In early-stage CRC, MSI can select a group of tumors with a better prognosis, while in metastatic disease it seems to confer a negative prognosis. Although with conflicting results, a large amount of preclinical and clinical evidence suggests a possible resistance to 5-FU in these tumors. The higher mutational load in MSI-H CRC can elicit an endogenous immune anti-tumor response, counterbalanced by the expression of immune inhibitory signals, such as PD-1 or PD-L1, that resist tumor elimination. Based on these considerations, MSI-H CRCs seem to be particularly responsive to immunotherapy, such as anti-PD-1, opening a new era in the treatment landscape for patients with metastatic CRC.

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Metadata

Authors
Gelsomino, F., Barbolini, M., Spallanzani, A., Pugliese, G., & Cascinu, S.
Venue
Cancer Treatment Reviews
Publisher
Elsevier BV
Published
2016-12
Volume
51
Pages
19-26
ISSN
0305-7372 (ISSN-L)
DOI
10.1016/j.ctrv.2016.10.005
OpenAlex
W2546257383
Cited by
313
References
88
FWCI
18.76
Type
journal article
Language
en
Open access
green

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