The added value of PMS2 immunostaining in the diagnosis of hereditary nonpolyposis colorectal cancer.

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The added value of PMS2 immunostaining in the diagnosis of hereditary nonpolyposis colorectal cancer. / Halvarsson, Britta; Lindblom, Annika; Rambech, Eva; Lagerstedt, Kristina; Nilbert, Mef.

I: Familial Cancer, Vol. 5, Nr. 4, 2006, s. 353-358.

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Halvarsson, Britta ; Lindblom, Annika ; Rambech, Eva ; Lagerstedt, Kristina ; Nilbert, Mef. / The added value of PMS2 immunostaining in the diagnosis of hereditary nonpolyposis colorectal cancer. I: Familial Cancer. 2006 ; Vol. 5, Nr. 4. s. 353-358.

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TY - JOUR

T1 - The added value of PMS2 immunostaining in the diagnosis of hereditary nonpolyposis colorectal cancer.

AU - Halvarsson, Britta

AU - Lindblom, Annika

AU - Rambech, Eva

AU - Lagerstedt, Kristina

AU - Nilbert, Mef

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Oncology, MV (013035000), Pathology, (Lund) (013030000)

PY - 2006

Y1 - 2006

N2 - dentification and characterization of the genetic background in patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome is important since control programmes can in a cost-effective manner prevent cancer development in high-risk individuals. HNPCC is caused by germline mismatch repair (MMR) gene mutations and the genetic analysis of HNPCC therefore includes assessment of microsatellite instability (MSI) and immunohistochemical MMR protein expression in the tumor tissue. MSI is found in >95% of the HNPCC-associated tumors and immunostaining using antibodies against the MMR proteins MLH1, MSH2, and MSH6 has been found to correctly pinpoint the affected gene in about 90% of the cases. The PMS2 antibody was the most recently developed and we have in a clinical material assessed the added value of PMS2 immunostaining in 213 patients with suspected hereditary colorectal cancer. All 119 MSS tumors showed retained expression for all four antibodies and PMS2 did thus not identify any underlying MMR defect in these cases. However, PMS2 immunostaining contributed to the characterization of the MMR defect in a subset of the MSI tumors. Concomitant loss of MLH1 and PMS2, which functionally interact in the MutL alpha complex, was found in 98% of the tumors from patients with germline MLH1 mutations. Among the 12 MSI-high tumors with retained expression of MLH1, MSH2 and MSH6, 8 tumors showed loss of PMS2 staining, and mutations in MLH1 were identified in 2 and mutations in PMS2 in 3 of these individuals. In summary, isolated loss of PMS2 was found in 8% of the MSI-high tumors in our series, including 8/12 previously unexplained MSI-high tumors, in which mutations either in MLH1 or in PMS2 were identified in five cases.

AB - dentification and characterization of the genetic background in patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome is important since control programmes can in a cost-effective manner prevent cancer development in high-risk individuals. HNPCC is caused by germline mismatch repair (MMR) gene mutations and the genetic analysis of HNPCC therefore includes assessment of microsatellite instability (MSI) and immunohistochemical MMR protein expression in the tumor tissue. MSI is found in >95% of the HNPCC-associated tumors and immunostaining using antibodies against the MMR proteins MLH1, MSH2, and MSH6 has been found to correctly pinpoint the affected gene in about 90% of the cases. The PMS2 antibody was the most recently developed and we have in a clinical material assessed the added value of PMS2 immunostaining in 213 patients with suspected hereditary colorectal cancer. All 119 MSS tumors showed retained expression for all four antibodies and PMS2 did thus not identify any underlying MMR defect in these cases. However, PMS2 immunostaining contributed to the characterization of the MMR defect in a subset of the MSI tumors. Concomitant loss of MLH1 and PMS2, which functionally interact in the MutL alpha complex, was found in 98% of the tumors from patients with germline MLH1 mutations. Among the 12 MSI-high tumors with retained expression of MLH1, MSH2 and MSH6, 8 tumors showed loss of PMS2 staining, and mutations in MLH1 were identified in 2 and mutations in PMS2 in 3 of these individuals. In summary, isolated loss of PMS2 was found in 8% of the MSI-high tumors in our series, including 8/12 previously unexplained MSI-high tumors, in which mutations either in MLH1 or in PMS2 were identified in five cases.

KW - PMS2

KW - HNPCC

KW - immunostaining

KW - hereditary nonpolyposis colorectal cancer

U2 - 10.1007/s10689-006-0005-9

DO - 10.1007/s10689-006-0005-9

M3 - Article

C2 - 16817031

VL - 5

SP - 353

EP - 358

JO - Familial Cancer

JF - Familial Cancer

SN - 1389-9600

IS - 4

ER -