Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function

Louise Klarskov; Susanne Holck; Inge Bernstein; Henrik Okkels; Eva Rambech; Bo Baldetorp; Mef Nilbert

doi:10.1097/PAS.0b013e318225c3f0

Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function

Louise Klarskov, Susanne Holck, Inge Bernstein, Henrik Okkels, Eva Rambech, Bo Baldetorp, Mef Nilbert

22 Citations (Scopus)

Abstract

Identification of Lynch syndrome tumors is challenging. This relates particularly to MSH6-associated cases, which show reduced penetrance of colorectal cancer and a higher age at diagnosis. We recorded the clinical and morphologic features of 52 MSH6-associated colorectal cancers in comparison with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite instability and loss of immunohistochemical MSH6 expression. The remaining 8% showed a mismatch repair-stable phenotype, which suggests that analysis of additional tumors might be considered in families suspected of Lynch syndrome.

Original language	English
Journal	American Journal of Surgical Pathology
Volume	35
Issue number	9
Pages (from-to)	1391-9
Number of pages	9
ISSN	0147-5185
DOIs	https://doi.org/10.1097/PAS.0b013e318225c3f0
Publication status	Published - 1 Sept 2011

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Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function. / Klarskov, Louise; Holck, Susanne; Bernstein, Inge et al.
In: American Journal of Surgical Pathology, Vol. 35, No. 9, 01.09.2011, p. 1391-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Klarskov, L, Holck, S, Bernstein, I, Okkels, H, Rambech, E, Baldetorp, B & Nilbert, M 2011, 'Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function', American Journal of Surgical Pathology, vol. 35, no. 9, pp. 1391-9. https://doi.org/10.1097/PAS.0b013e318225c3f0

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abstract = "Identification of Lynch syndrome tumors is challenging. This relates particularly to MSH6-associated cases, which show reduced penetrance of colorectal cancer and a higher age at diagnosis. We recorded the clinical and morphologic features of 52 MSH6-associated colorectal cancers in comparison with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite instability and loss of immunohistochemical MSH6 expression. The remaining 8% showed a mismatch repair-stable phenotype, which suggests that analysis of additional tumors might be considered in families suspected of Lynch syndrome.",

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AU - Rambech, Eva

AU - Baldetorp, Bo

AU - Nilbert, Mef

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AB - Identification of Lynch syndrome tumors is challenging. This relates particularly to MSH6-associated cases, which show reduced penetrance of colorectal cancer and a higher age at diagnosis. We recorded the clinical and morphologic features of 52 MSH6-associated colorectal cancers in comparison with MLH1/MSH2-mutant tumors and sporadic mismatch repair-deficient cancers. In the MSH6 subset, we confirmed a higher age (median, 56 y) at diagnosis and found a significantly larger proportion (25%) of rectal cancers. Presence of dirty necrosis was the sole histologic component that significantly differed between MSH6 and MLH1/MSH2 tumors. Compared with the sporadic mismatch repair-defective cohort, MSH6 cases had a lower prevalence of tumor-infiltrating lymphocytes and Crohn-like reactions. Mismatch repair defects were identified in 92% of MSH6 tumors, with high concordance between microsatellite instability and loss of immunohistochemical MSH6 expression. The remaining 8% showed a mismatch repair-stable phenotype, which suggests that analysis of additional tumors might be considered in families suspected of Lynch syndrome.

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Challenges in the identification of MSH6-associated colorectal cancer: rectal location, less typical histology, and a subset with retained mismatch repair function

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