March 2016 Quiz 2

Q2: ANSWER: E

Critique

These results could be due to Lynch syndrome as a result of an EPCAM mutation. With hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, patients are at an increased risk for colorectal and several other cancers owing to inactivating germline mutations in mismatch repair genes (MMR), including MLH1, MSH2, MSH6, and PMS2. Germline EPCAM deletions in the 3’ region can cause HNPCC. The EPCAM deletions lead to methylation of the MSH2 promoter and ultimately silencing of MSH2 gene. Silencing of the MSH2 gene results in a pattern of MSH2 and MSH6 loss on immunohistochemistry. Since immunohistochemistry shows no loss of expression of MLH1 or PMS2 proteins, this indicates the absence of a mutation in MLH1 and PMS2 genes. The presence of high microsatellite instability and loss of expression of two mismatch repair proteins indicates the presence of Lynch syndrome and not a sporadic colorectal cancer. Therefore MLH1 hypermethylation and BRAF testing is not indicated.

Reference

1. Umar A., Boland C., Terdiman J.P., et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261-8.

Q2: ANSWER: E

Critique

These results could be due to Lynch syndrome as a result of an EPCAM mutation. With hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, patients are at an increased risk for colorectal and several other cancers owing to inactivating germline mutations in mismatch repair genes (MMR), including MLH1, MSH2, MSH6, and PMS2. Germline EPCAM deletions in the 3’ region can cause HNPCC. The EPCAM deletions lead to methylation of the MSH2 promoter and ultimately silencing of MSH2 gene. Silencing of the MSH2 gene results in a pattern of MSH2 and MSH6 loss on immunohistochemistry. Since immunohistochemistry shows no loss of expression of MLH1 or PMS2 proteins, this indicates the absence of a mutation in MLH1 and PMS2 genes. The presence of high microsatellite instability and loss of expression of two mismatch repair proteins indicates the presence of Lynch syndrome and not a sporadic colorectal cancer. Therefore MLH1 hypermethylation and BRAF testing is not indicated.

Reference

1. Umar A., Boland C., Terdiman J.P., et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261-8.

Q2: ANSWER: E

Critique

These results could be due to Lynch syndrome as a result of an EPCAM mutation. With hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, patients are at an increased risk for colorectal and several other cancers owing to inactivating germline mutations in mismatch repair genes (MMR), including MLH1, MSH2, MSH6, and PMS2. Germline EPCAM deletions in the 3’ region can cause HNPCC. The EPCAM deletions lead to methylation of the MSH2 promoter and ultimately silencing of MSH2 gene. Silencing of the MSH2 gene results in a pattern of MSH2 and MSH6 loss on immunohistochemistry. Since immunohistochemistry shows no loss of expression of MLH1 or PMS2 proteins, this indicates the absence of a mutation in MLH1 and PMS2 genes. The presence of high microsatellite instability and loss of expression of two mismatch repair proteins indicates the presence of Lynch syndrome and not a sporadic colorectal cancer. Therefore MLH1 hypermethylation and BRAF testing is not indicated.

Reference

1. Umar A., Boland C., Terdiman J.P., et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261-8.