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Current hypotheses on how microsatellite instability leads to enhanced survival of Lynch Syndrome patients.

Drescher KM, Sharma P, Lynch HT - Clin. Dev. Immunol. (2010)

Bottom Line: High levels of microsatellite instability (MSI-high) are a cardinal feature of colorectal tumors from patients with Lynch Syndrome.Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS) colorectal cancer.Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA. kdresche@creighton.edu

ABSTRACT
High levels of microsatellite instability (MSI-high) are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS) colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.

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Related in: MedlinePlus

Tumors from Lynch Syndrome patients experience increased infiltration of tumors with CD3+ lymphocytes (b) compared to non-Lynch Syndrome patients (a).
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fig1: Tumors from Lynch Syndrome patients experience increased infiltration of tumors with CD3+ lymphocytes (b) compared to non-Lynch Syndrome patients (a).

Mentions: The potential positive impact on disease outcome that dense infiltration of lymphocytes in various tumors has been a subject of considerable debate and speculation [30–33, 39–50]. A recent study of CRCs that did not take into consideration the MSI status of the tumor found that patients with tumors infiltrated with increased levels of cytotoxic and memory (CD45RO+) T cells had improved outcome as compared with patients with low levels of cytotoxic and memory T cells [50]. This particular study focused on patients with stage I and II CRC. Several studies have examined MSI-high colorectal carcinomas and characterized both the number and phenotype of the tumor infiltrating cells [30, 31, 41, 43, 47–49, 101, 102]. Studies by Smyrk et al. described an increased level of tumor infiltrating lymphocytes (TILs) in CRCs with high levels of microsatellite instability. In this study, TIL's in MSS, MSI-low and MSI-high CRCs were correlated with microsatellite status, and it was determined that tumors from HNPCC and other MSI-high CRCs had increased lymphocyte infiltration compared to MSI-low or MSS tumors [47] (Figure 1).


Current hypotheses on how microsatellite instability leads to enhanced survival of Lynch Syndrome patients.

Drescher KM, Sharma P, Lynch HT - Clin. Dev. Immunol. (2010)

Tumors from Lynch Syndrome patients experience increased infiltration of tumors with CD3+ lymphocytes (b) compared to non-Lynch Syndrome patients (a).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2901607&req=5

fig1: Tumors from Lynch Syndrome patients experience increased infiltration of tumors with CD3+ lymphocytes (b) compared to non-Lynch Syndrome patients (a).
Mentions: The potential positive impact on disease outcome that dense infiltration of lymphocytes in various tumors has been a subject of considerable debate and speculation [30–33, 39–50]. A recent study of CRCs that did not take into consideration the MSI status of the tumor found that patients with tumors infiltrated with increased levels of cytotoxic and memory (CD45RO+) T cells had improved outcome as compared with patients with low levels of cytotoxic and memory T cells [50]. This particular study focused on patients with stage I and II CRC. Several studies have examined MSI-high colorectal carcinomas and characterized both the number and phenotype of the tumor infiltrating cells [30, 31, 41, 43, 47–49, 101, 102]. Studies by Smyrk et al. described an increased level of tumor infiltrating lymphocytes (TILs) in CRCs with high levels of microsatellite instability. In this study, TIL's in MSS, MSI-low and MSI-high CRCs were correlated with microsatellite status, and it was determined that tumors from HNPCC and other MSI-high CRCs had increased lymphocyte infiltration compared to MSI-low or MSS tumors [47] (Figure 1).

Bottom Line: High levels of microsatellite instability (MSI-high) are a cardinal feature of colorectal tumors from patients with Lynch Syndrome.Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS) colorectal cancer.Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA. kdresche@creighton.edu

ABSTRACT
High levels of microsatellite instability (MSI-high) are a cardinal feature of colorectal tumors from patients with Lynch Syndrome. Other key characteristics of Lynch Syndrome are that these patients experience fewer metastases and have enhanced survival when compared to patients diagnosed with microsatellite stable (MSS) colorectal cancer. Many of the characteristics associated with Lynch Syndrome including enhanced survival are also observed in patients with sporadic MSI-high colorectal cancer. In this review we will present the current state of knowledge regarding the mechanisms that are utilized by the host to control colorectal cancer in Lynch Syndrome and why these same mechanisms fail in MSS colorectal cancers.

Show MeSH
Related in: MedlinePlus