Immunohistochemical evaluation of microsatellite instability in resected colorectal liver metastases: a preliminary experience


In this retrospective study, we evaluated the predictive role of different immunohistochemical expression (IHC) of the mismatch repair proteins (MMR) in patients with colorectal liver metastasis (CRLM) submitted to liver resection. A total of 108 patients were retrieved, and 15 patients were excluded from the study because of the impossibility to obtain adequate formalin-fixed tissue blocks. The final analysis included 93 patients. Twenty-eight cases (30%) presented a no loss of expression or microsatellite stability (MSS) status, 59 cases (63%) showed a hybrid loss of expression, while 6 cases (7%) presented a complete loss of expression or microsatellite instability status (MSI). Patients with complete or hybrid loss of expression of MMR developed a high intra-hepatic recurrence rate compared to other ones (54% vs 21% OR of 4.278, 95% CI 1.53–11.93) (p = 0.004). The same difference in terms of liver recurrence has been found among patients with R0 resection (50% vs 17% OR of 0.2, 95% CI 0.06–0.65) (p = 0.005). However, there was no difference in terms of disease-free survival and overall survival. Complete or hybrid loss of expression of MMR could be considered a risk factor for intra-hepatic recurrences after liver resections for CRLM.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2



Immunohistochemical expression


Mismatch repair proteins


Colorectal liver metastasis


Microsatellite instability status


Portal vein embolization


Two-stage hepatectomy


Associating liver partition with portal vein ligation for staged hepatectomy


Disease-free survival


Overall survival


Future liver remnant


Lynch syndrome


  1. 1.

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Moris D, Lu L, Qian S. Mechanisms of liver-induced tolerance. Curr Opin Organ Transplant. 2017;22(1):71–8.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Jegatheeswaran S, Mason JM, Hancock HC, Siriwardena AK. The liver-first approach to the management of colorectal cancer with synchronous hepatic metastases: a systematic review. JAMA Surg. 2013;148(4):385–91.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Adam R, de Gramont A, Figueras J, Kokudo N, Kunstlinger F, Loyer E, Poston G, Rougier P, Rubbia-Brandt L, Sobrero A, Teh C, Tejpar S, Van Cutsem E, Vauthey JN, Påhlman L. EGOSLIM (Expert Group on Onco Surgery management of Liver Metastases) group Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus. Cancer Treat Rev. 2015;41(9):729–41.

    Article  PubMed  Google Scholar 

  5. 5.

    Liu W, Sun Y, Zhang L, Xing BC. Negative surgical margin improved long-term survival of colorectal cancer liver metastases after hepatic resection: a systematic review and meta-analysis. Int J Colorectal Dis. 2015;30(10):1365–73.

    Article  PubMed  Google Scholar 

  6. 6.

    Adams RB, Haller DG, Roh MS. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006;13(10):1281–3.

    Article  PubMed  Google Scholar 

  7. 7.

    Imai K, Adam R, Baba H. How to increase the resectability of initially unresectable colorectal liver metastases: A surgical perspective. Ann Gastroenterol Surg. 2019;3(5):476–86.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Serrano PE, Gu CS, Husien M, Jalink D, Ritter A, Martel G, Tsang ME, Law CH, Hallet J, McAlister V, Sela N, Solomon H, Moulton CA, Gallinger S, Levine M. Risk factors for survival following recurrence after first liver resection for colorectal cancer liver metastases. J Surg Oncol. 2019.

    Article  PubMed  Google Scholar 

  9. 9.

    Baretti M, Le DT. DNA mismatch repair in cancer. Pharmacol Ther. 2018;189:45–62.

    CAS  Article  Google Scholar 

  10. 10.

    Vilar E, Gruber SB. Microsatellite instability in colorectal cancer-the stable evidence. Nat Rev Clin Oncol. 2010;7(3):153–62.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, French AJ, Kabat B, Foster NR, Torri V, Ribic C, Grothey A, Moore M, Zaniboni A, Seitz JF, Sinicrope F, Gallinger S. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28(20):3219–26.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Yamashita S, Chun YS, Kopetz SE, Vauthey JN. Biomarkers in colorectal liver metastases. Br J Surg. 2018;105(6):618–27.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Kawakami H, Zaanan A, Sinicrope F. MSI testing and its role in the management of colorectal cancer. Curr treat Options Oncol. 2015.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Zhang L, Peng Y, Peng G. Mismatch repair-based stratification for immune checkpoint blockade therapy. Am J Cancer Re. 2018;8(10):1977–88.

    CAS  Google Scholar 

  15. 15.

    National Comprehensive Cancer Network (NCCN) guidelines colon cancer, version 3.2019.

  16. 16.

    Pietrantonio F, Petrelli F, Coinu A, Di Bartolomeo M, Borgonovo K, Maggi C, Cabiddu M, Iacovelli R, Bossi I, Lonati V, Ghilardi M, de Braud F, Barni S. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer. 2015;51(5):587–94.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Parsons MT1, Buchanan DD, Thompson B, Young JP, Spurdle AB. Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet. 2012;49(3):151–7.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information




BM, PG, TD and OE designed the study; BM, PG, TD, MR and OE performed the research; SR analyzed the data; BM, PG, TD, MR and OE wrote the paper; all authors critically reviewed the article, read and approved the contents.

Corresponding author

Correspondence to Barabino Matteo.

Ethics declarations

Conflict of interest

The corresponding author declares that the manuscript is submitted on behalf of all authors. All the authors declare that they have no competing interests.

Informed consent

All involved persons gave their verbal and written informed consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Matteo, B., Gaetano, P., Delfina, T. et al. Immunohistochemical evaluation of microsatellite instability in resected colorectal liver metastases: a preliminary experience. Med Oncol 37, 63 (2020).

Download citation


  • Microsatellite instability,
  • Immunohistochemical evaluation
  • Colorectal liver metastases