OBJECTIVE: To determine the value of histology in identifying Lynch syndrome among those patients with early onset of colorectal cancer (CRC). METHODS: Demographic, clinical and cancer history data from patients diagnosed with CRC before 60 years of age, and treated at our institution between 1997 and 2005, were collected from medical records and direct interview. Their tumors were assessed to identify histological features suggestive of high frequency microsatellite instability (MSI-H): tumor infiltrating lymphocytes, Crohn's like inflammatory reaction, mucinous, signet ring cells, medullary growth pattern and then, tested for microsatellite instability (MSI) and MLH1/ MSH2 protein expression. RESULTS: Sixty-five patients were included in the study. The mean age at diagnosis was 48 +/- 9.9 years. Overall, 28 (43%) patients, including 13 of 35 diagnosed between ages 50 and 60, had tumor demonstrating one or more histological features suggestive of MSI-H. These patients were younger (45 vs. 50 years, P = 0.02) and more commonly had family history of Lynch syndrome-related cancers (36 vs. 19%), though the latter feature did not reach statistical significance (P = 0.07). Eleven of 25 tumors with MSI-H histology, but only 1 of 29 tumors without special histological features were found to be MSI-H (P < 0.0001). Histology had a positive predictive value of 44% and a negative predictive value of 97% for identifying MSI-H tumors. CONCLUSIONS: Limiting MSI analysis only to those tumors with suggestive histology would have reduced the need for testing by nearly 60% of all tumors from patients that met the revised Bethesda guidelines.
OBJECTIVE: To determine the value of histology in identifying Lynch syndrome among those patients with early onset of colorectal cancer (CRC). METHODS: Demographic, clinical and cancer history data from patients diagnosed with CRC before 60 years of age, and treated at our institution between 1997 and 2005, were collected from medical records and direct interview. Their tumors were assessed to identify histological features suggestive of high frequency microsatellite instability (MSI-H): tumor infiltrating lymphocytes, Crohn's like inflammatory reaction, mucinous, signet ring cells, medullary growth pattern and then, tested for microsatellite instability (MSI) and MLH1/ MSH2 protein expression. RESULTS: Sixty-five patients were included in the study. The mean age at diagnosis was 48 +/- 9.9 years. Overall, 28 (43%) patients, including 13 of 35 diagnosed between ages 50 and 60, had tumor demonstrating one or more histological features suggestive of MSI-H. These patients were younger (45 vs. 50 years, P = 0.02) and more commonly had family history of Lynch syndrome-related cancers (36 vs. 19%), though the latter feature did not reach statistical significance (P = 0.07). Eleven of 25 tumors with MSI-H histology, but only 1 of 29 tumors without special histological features were found to be MSI-H (P < 0.0001). Histology had a positive predictive value of 44% and a negative predictive value of 97% for identifying MSI-H tumors. CONCLUSIONS: Limiting MSI analysis only to those tumors with suggestive histology would have reduced the need for testing by nearly 60% of all tumors from patients that met the revised Bethesda guidelines.
Authors: J Wijnen; H van der Klift; H Vasen; P M Khan; F Menko; C Tops; H Meijers Heijboer; D Lindhout; P Møller; R Fodde Journal: Nat Genet Date: 1998-12 Impact factor: 38.330
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