Abstract
4118 Background: Microsatellite instability (MSI) is present in 10–20% of patients (pts) with non-hereditary colorectal cancer (CRC) and is generally associated with improved overall survival. The effect of chemotherapy in such pts is uncertain, and most data are derived from early stage CRC. Therefore the outcome of treatment in relation to presence or absence of MSI was studied in pts with non- hereditary advanced CRC. Methods: Data were collected from previously untreated advanced CRC pts randomized between 1st line capecitabine (Cap), 2nd line irinotecan (Iri), and 3rd line Cap + oxaliplatin (CapOx) vs 1st line CapIri and 2nd line CapOx. Formalin-fixed, paraffin embedded blocks of primary tumors and normal tissue were collected and tissue microarrays were made. Expression of the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 was examined by immunohistochemistry. Additionally MSI analysis and hypermethylation of the MLH1-promoter were performed. Pts with a tumor showing MSI caused by hypermethylation of the MLH1-promoter were included to study the correlation between MSI status and response to 1st line treatment and overall survival. Results: MSI caused by hypermethylation of the MLH1-promoter was found in 14 (3%) of 512 eligible pts. In 461 evaluable pts, disease control (CR+PR+SD=4 months) in 12 pts with MSI was 58% [95% CI 28%- 85%] and in 449 without MSI 83% [95% CI 79%-86%, p= 0.03].The median OS in pts with MSI was 7 months [95% CI 4–17] and in pts without MSI 18 months [95% CI 16–19, log rank p=0.08]. Conclusions: MSI in advanced non-hereditary CRC is very rare, and predicts a significantly worse outcome in terms of response to chemotherapy with a trend towards a decreased OS. No significant financial relationships to disclose.
Published Version
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