BACKGROUND AND AIM: The aim of the present study was to evaluate associations between mismatch repair (MMR) status and clinicopathological characteristics and prognosis using immunohistochemistry (IHC) and microsatellite instability (MSI) analyses in a prospective cohort of a large number of accumulated samples. METHODS: Tumor tissue samples obtained during curative surgery (n = 2028) were analyzed using both MLH1/MSH2 IHC and MSI assays. Clinicopathological parameters and survival outcomes were compared according to IHC and MSI results. The median follow-up period was 43 months (range: 1-85 months). RESULTS: IHC identified 207 tumor samples (10.2%) with a loss of either MLH1 or MSH2 expression. The MSI analysis identified 203 tumor samples (10%) with high-frequency MSI (MSI-H). Patients with MMR defects were younger, and had tumors characterized by right-colon predilection; large-size, infrequent lymph node metastasis; poorly-differentiated or mucinous histology, and synchronous adenomas (P < 0.001-0.008). Patients with MSI-H status had higher 4-year disease-free survival rates than patients with microsatellite stable status (90.8% vs 80.6%, P = 0.001). A multivariate analysis showed that MSI-H status was a good prognostic factor for recurrence (hazard ratio: 0.48, 95% confidence interval: 0.30-0.83, P = 0.007). CONCLUSIONS: Patients with MMR defects had distinct clinicopathological characteristics, including a lower risk of recurrence. IHC and MSI analyses provided complementary information regarding specific clinicopathological parameters and prognosis.
BACKGROUND AND AIM: The aim of the present study was to evaluate associations between mismatch repair (MMR) status and clinicopathological characteristics and prognosis using immunohistochemistry (IHC) and microsatellite instability (MSI) analyses in a prospective cohort of a large number of accumulated samples. METHODS:Tumor tissue samples obtained during curative surgery (n = 2028) were analyzed using both MLH1/MSH2 IHC and MSI assays. Clinicopathological parameters and survival outcomes were compared according to IHC and MSI results. The median follow-up period was 43 months (range: 1-85 months). RESULTS: IHC identified 207 tumor samples (10.2%) with a loss of either MLH1 or MSH2 expression. The MSI analysis identified 203 tumor samples (10%) with high-frequency MSI (MSI-H). Patients with MMR defects were younger, and had tumors characterized by right-colon predilection; large-size, infrequent lymph node metastasis; poorly-differentiated or mucinous histology, and synchronous adenomas (P < 0.001-0.008). Patients with MSI-H status had higher 4-year disease-free survival rates than patients with microsatellite stable status (90.8% vs 80.6%, P = 0.001). A multivariate analysis showed that MSI-H status was a good prognostic factor for recurrence (hazard ratio: 0.48, 95% confidence interval: 0.30-0.83, P = 0.007). CONCLUSIONS:Patients with MMR defects had distinct clinicopathological characteristics, including a lower risk of recurrence. IHC and MSI analyses provided complementary information regarding specific clinicopathological parameters and prognosis.
Authors: Tiziana Grassi; Angelo Calcagno; Stefania Marzinotto; Ambrogio P Londero; Maria Orsaria; Gioia N Canciani; Carlo Alberto Beltrami; Diego Marchesoni; Laura Mariuzzi Journal: Int J Clin Exp Pathol Date: 2015-02-01