Familial Cancer

, Volume 15, Issue 2, pp 253–260

Mismatch repair deficiency concordance between primary colorectal cancer and corresponding metastasis

  • Sigurdis Haraldsdottir
  • Rachel Roth
  • Rachel Pearlman
  • Heather Hampel
  • Christina A. Arnold
  • Wendy L. Frankel
Original Article

DOI: 10.1007/s10689-015-9856-2

Cite this article as:
Haraldsdottir, S., Roth, R., Pearlman, R. et al. Familial Cancer (2016) 15: 253. doi:10.1007/s10689-015-9856-2

Abstract

Universal screening for mismatch repair deficiency (dMMR) in cancer is increasingly being implemented to detect Lynch syndrome and aid in treatment decisions. The mismatch repair (MMR) immunohistochemistry (IHC) concordance rate between primary colorectal cancer (CRC) and metastasis is unknown. At times, only metastatic tumor is available for screening (lymph node, liver, lung etc.) rather than the primary tumor. Therefore, it is important to confirm that tissue from metastases can be used for screening for dMMR. We tested dMMR primary and metastatic tumor to assess concordance between the two. We identified dMMR CRC resected at Ohio State University from 1999 to 2013 and stained a corresponding metastasis for all four MMR proteins (MLH1, MSH2, MSH6, PMS2) with IHC. A total of 50 primary CRC with dMMR and available regional lymph nodes (LN; 26 cases) or other metastatic tissue (24 cases) were identified. Thirteen cases were explained by MLH1 hypermethylation and 10 cases had Lynch syndrome. Two cases had somatic MMR mutations and the etiology for dMMR was unknown in 25 cases. All cases showed concordance in IHC staining between the primary tumor and corresponding metastatic tissue. In 36 cases, metastatic LN/other site was resected at the same time as the primary tumor. In 14 cases, time lapsed [median 16.5 months; quartile (Q)1 8.0; Q3 25; range 3–69] from the primary resection until metastatic resection. Metastatic tissue can be used to screen for Lynch syndrome and dMMR.

Keywords

Deficient mismatch repair system Lynch syndrome Immunohistochemistry Metastatic cancer Colorectal cancer Concordance 

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Sigurdis Haraldsdottir
    • 1
  • Rachel Roth
    • 2
  • Rachel Pearlman
    • 3
  • Heather Hampel
    • 3
  • Christina A. Arnold
    • 2
  • Wendy L. Frankel
    • 2
  1. 1.Division of Medical Oncology, Department of Internal MedicineStanford UniversityStanfordUSA
  2. 2.Department of PathologyOhio State University Medical CenterColumbusUSA
  3. 3.Division of Human Genetics, Department of Internal MedicineOhio State University Medical CenterColumbusUSA