Invasion pattern and histologic features of tumor aggressiveness correlate with MMR protein expression, but are independent of activating KRAS and BRAF mutations in CRC
KRAS / BRAF mutation testing and mismatch repair (MMR) protein immunohistochemistry have an established role in routine diagnostic evaluation of colorectal carcinoma (CRC). However, since the exact impact of these molecular characteristics on tumor morphology and behavior is still subject to researc...
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Published in | Virchows Archiv : an international journal of pathology Vol. 465; no. 2; pp. 155 - 163 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.08.2014
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | KRAS
/
BRAF
mutation testing and mismatch repair (MMR) protein immunohistochemistry have an established role in routine diagnostic evaluation of colorectal carcinoma (CRC). However, since the exact impact of these molecular characteristics on tumor morphology and behavior is still subject to research, the aim of our study was to examine associations between molecular and morphologic features that had not been analyzed in this combination before.
KRAS
(codons 12, 13, and 61) and
BRAF
(codon 600) mutation status and MMR protein expression were analyzed in a consecutive series of 117 CRC samples using DNA pyrosequencing and immunohistochemistry. Tumor cell budding, infiltration pattern, and peritumoral lymphocytic (PTL) reaction was assessed applying established criteria. Molecular and morphological findings were correlated applying chi-square and Fisher’s exact test. We found
KRAS
or
BRAF
mutations in 40 and 8 % of samples, while loss of MMR protein expression was observed in 11 %. Tumor budding was significantly associated with infiltrative growth, absence of PTLs, and blood and lymph vessel infiltration. Neither
KRAS
nor
BRAF
mutations were associated with a certain growth pattern or budding intensity of CRC, but loss of MMR protein expression was found in context with
BRAF
mutation, expanding growth, and presence of PTLs. Our results confirm an association between loss of MMR protein expression, presence of activating
BRAF
mutation, expanding growth, and PTL reaction as well as between tumor budding, infiltrative growth pattern, and tumor aggressiveness; however, there was no such association between the presence of an activating
KRAS
or
BRAF
mutation and a distinct invasion pattern or tumor aggressiveness in CRC. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0945-6317 1432-2307 |
DOI: | 10.1007/s00428-014-1604-8 |