Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic.
Br J Surg
; 91(4): 469-75, 2004 Apr.
Article
in En
| MEDLINE
| ID: mdl-15048750
ABSTRACT
BACKGROUND:
Patients with colorectal cancer that display high-level microsatellite instability (MSI-H) appear to have a better prognosis. This may be explained by the pronounced T cell infiltrate seen in MSI-H tumours that is related to a specific antigen-driven immune response. The nature of tumour-infiltrating lymphocytes in colorectal cancers was investigated using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry.METHODS:
Quantitative fluorescent hydrolysis probe-based reverse transcriptase-PCR assays were used to detect levels of mRNA specifying T cell markers in fresh frozen colorectal tissue from MSI-H tumours and those with little or no microsatellite instability (microsatellite stable (MSS) tumours). In addition, immunohistochemistry was performed on paraffin-embedded sections to compare expression of the same T cell markers and the activation markers granzyme B and interleukin 2 receptor alpha-subunit (IL-2Ralpha) in MSI-H and MSS tumours.RESULTS:
MSI-H tumours contained higher ratios of CD8/CD3 mRNA copy numbers than MSS tumours (P = 0.016), confirming the cytotoxic nature of lymphocyte infiltrates in this subset of colorectal cancers. Furthermore, immunohistochemistry confirmed that MSI-H tumours contained more infiltrating lymphocytes than MSS tumours, as shown by increased expression of CD3 (P = 0.003) and CD8 (P = 0.008). Consistent with other studies, the lymphocytes in MSI-H tumours were activated as indicated by significantly higher granzyme B counts (P = 0.020) and a significantly higher level of expression of IL-2Ralpha (P = 0.017).CONCLUSION:
The results support the hypothesis that MSI-H colorectal cancers may be more immunogenic than MSS tumours.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Lymphocytes, Tumor-Infiltrating
/
Microsatellite Repeats
Type of study:
Prognostic_studies
Limits:
Aged
/
Female
/
Humans
/
Male
Language:
En
Journal:
Br J Surg
Year:
2004
Document type:
Article
Affiliation country: