Pathological and molecular features of liver metastases of colon adenocarcinoma
https://doi.org/10.16931/1995-5464.2019412-17
Abstract
Aim. To study pathological and molecular features of liver metastases of colon adenocarcinoma.
Material and methods. DNA mismatch repair (MMR), CXCR4 expression, Ki-67 proliferative activity were investigated in 125 cases of colon adenocarcinoma with liver metastases. First group consisted of 94 cases of tumor with liver metastases at diagnosis. The second group consisted of 31 cases with stage II disease at diagnosis, but subsequently these patient metastases. In second group KRAS mutation was investigated. The control group included 22 cases of stage II colon adenocarcinoma without disease progression. MMR was studied in 325 cases of colon adenocarcinoma without known stage.
Results. MMR deficiency (dMMR) didn’t revealed in group 1 and 2. The frequency of deficiency MMR in the general population of colon adenocarcinoma was 8%. Low level of expression of CXCR4 in group I and II was revealed in 16% of cases, in control group – in 73%. Low level of Ki-67 was revealed in 5% of cases of liver metastases (group 1 and 2), the frequency of KRAS mutations was 45%.
Conclusion. Colon adenocarcinoma with liver metastases is characterized by aggressive immunophenotype: high expression rates CXCR4, Ki-67, and preferentially retained MMR function.
Material and methods. DNA mismatch repair (MMR), CXCR4 expression, Ki-67 proliferative activity were investigated in 125 cases of colon adenocarcinoma with liver metastases. First group consisted of 94 cases of tumor with liver metastases at diagnosis. The second group consisted of 31 cases with stage II disease at diagnosis, but subsequently these patient metastases. In second group KRAS mutation was investigated. The control group included 22 cases of stage II colon adenocarcinoma without disease progression. MMR was studied in 325 cases of colon adenocarcinoma without known stage.
Results. MMR deficiency (dMMR) didn’t revealed in group 1 and 2. The frequency of deficiency MMR in the general population of colon adenocarcinoma was 8%. Low level of expression of CXCR4 in group I and II was revealed in 16% of cases, in control group – in 73%. Low level of Ki-67 was revealed in 5% of cases of liver metastases (group 1 and 2), the frequency of KRAS mutations was 45%.
Conclusion. Colon adenocarcinoma with liver metastases is characterized by aggressive immunophenotype: high expression rates CXCR4, Ki-67, and preferentially retained MMR function.
About the Authors
G. A. Raskin
Granov Russian Scientific Center of Radiology and Surgical Technologies,
Saint-Petersburg University
Russian Federation
Russian Federation
Doct. of Sci. (Med.), Head of Immunohistochemical Laboratory, Professor of Oncology Department
+7-812-596-90-73
70, Leningradskaya str., Pesochny, Saint-Petersburg, 197758, Russian Federation
7/9, University quay, Saint-Petersburg, 199034, Russian Federation
A. K. Ivanova
St.-Petersburg City Oncology Clinic
Russian Federation
Russian Federation
Oncologist
3/5, 2, Berezovaya alley, Saint-Petersburg, 197022, Russian Federation
M. S. Mukhina
Granov Russian Scientific Center of Radiology and Surgical Technologies
Russian Federation
Russian Federation
Cand. оf Sci. (Med.), Senior Researcher
70, Leningradskaya str., Pesochny, Saint-Petersburg, 197758, Russian Federation
R. V. Orlova
Saint-Petersburg University,
St.-Petersburg City Oncology Clinic
Russian Federation
Russian Federation
Doct. of Sci. (Med.), Professor, Head of Oncology Department, Chief Medical Oncologist
7/9, University quay, Saint-Petersburg, 199034, Russian Federation
3/5, 2, Berezovaya alley, Saint-Petersburg, 197022, Russian Federation
References
1. Valderrama-Treviño A.I., Barrera-Mera B., Ceballos-Villalva J., Montalvo-Javé E.E. Euroasian J Hepatogastroenterol. 2017; 7(2): 166–175. Doi: 10.5005/jp-journals-10018-1241.
2. Rothbarth J, van de Velde C. Treatment of liver metastases of colorectal cancer. Ann Oncol. 2005;16(Suppl 2):44–49. Doi: 10.1093/annonc/mdi702.
3. Lindor N.M., Burgart L.J., Leontovich O., Goldberg R.M., Cunningham J.M., Sargent D.J., Walsh-Vockley C., Petersen G.M., Walsh M.D., Leggett B.A., Young J.P., Barker M.A., Jass J.R., Hopper J., Gallinger S., Bapat B., Redston M., Thibodeau S.N. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol., 2002.,Vol. 20.: P.1043–1048. DOI: 10.1200/JCO.2002.20.4.1043.
4. Fujiyoshi K., Yamamoto G., Takenoya T., Takahashi A., Arai Y., Yamada M., Kakuta M., Yamaguchi K., Akagi Y., Nishimura Y., Sakamoto H., Akagi K. Metastatic pattern of stage IV colorectal cancer with high-frequency microsatellite instability as a prognostic factor. Anticancer Research. 2017. vol. 37, No. 1: 239-247. DOI: 10.21873/anticanres.11313.
5. Klingbiel D, Saridaki Z, Roth AD, Bosman FT, Delorenzi M, Tejpar S: Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial. Ann Oncol 2015. 26: 126-132. DOI: 10.1093/annonc/mdu499.
6. Ooki A, Akagi K, Yatsuoka T, Asayama M, Hara H, Takahashi A, Kakuta M, Nishimura Y, Yamaguchi K: Combined microsatellite instability and BRAF gene status as biomarkers for adjuvant chemotherapy in stage III colorectal cancer. J Surg Oncol. 2014. 110: 982-988. DOI: 10.1002/jso.23755.
7. Venderbosch S, Nagtegaal ID, Maughan TS, Smith CG, Cheadle JP, Fisher D, Kaplan R, Quirke P, Seymour MT, Richman SD, Meijer GA, Ylstra B, Heideman DA, de Haan AF, Punt CJ, Koopman M: Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies. Clin Cancer Res. 2014. 20: 5322-5330. DOI: 10.1158/1078-0432.CCR-14-0332.
8. Koizumi K, Hojo S., Akashi T., Yasumoto K., Saiki I. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response . Cancer Science. 2007. Vol.98. No11: 1652-1658. DOI: 10.1111/j.1349-7006.2007.00606.x.
9. Arya M., Ahmed H., Silhi N., Williamson M., Patel H.R. Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer cell migration. Tumour Biol. 2007. 28(3):123-131. DOI: 10.1159/000102979.
10. Zlotnik A. Involvement of chemokine receptors in organ-specific metastasis. Contrib. Microbiol. 2006. Vol. 13: 191-199. DOI: 10.1159/000092973.
11. Ashktorab H., Ahuja S., Kannan L., Llor X., Ellis N.A., Xicola R.M., Laiyemo A., Carethers J.M., Brim H., Nouraie M. A meta-analysis of MSI frequency and race in colorectal cancer. Oncotarget. 2016. 7(23): 34546–34557. DOI: 10.18632/oncotarget.8945.
12. Colorectal Cancer Facts & Figures 2017-2019. American Cancer Society, 2019.
13. Ribic C.M., Sargent D.J., Moore M.J., Thibodeau S.N., French A.J., Goldberg R.M., Hamilton S.R., Laurent-Puig P., Gryfe R., Shepherd L.E., Tu D., Redston M., Gallinger S. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003. 349:247-257. DOI: 10.1056/NEJMoa022289.
14. Xu C., Zheng L., Li D., Chen G., Gu J., Chen J., Yao Q. CXCR4 overexpression is correlated with poor prognosis in colorectal cancer. Life Sci. 2018. 208:333-340. DOI: 10.1016/j.lfs.2018.04.050.
15. Desurmont T., Skrypek N., Duhamel A., Jonckheere N., Millet G., Leteurtre E., Gosset P., Duchene B., Ramdane N., Hebbar M., Van Seuningen I., Pruvot F.R., Huet G., Truant S. Cancer Sci. 2015. 106(3):262-9. DOI: 10.1111/cas.12603.
16. Kim J, Takeuchi H, Lam ST, et al. Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol 2005. 23(12):2744–53. DOI: 10.1200/JCO.2005.07.078.
17. Melling N., Kowitz C.M., Simon R., Bokemeyer C., Terracciano L., Sauter G., Izbicki J.R., Marx A.H. High Ki67 expression is an independent good prognostic marker in colorectal cancer. J Clin Pathol. 2016. 69(3):209-14. DOI: 10.1136/jclinpath-2015-202985.
18. Luo Z-W., Zhu M.-G., Zhang Z.-Q., Ye F.0Y., Huang W.-H., Luo X.-Z. Increased expression of Ki-67 is a poor prognostic marker for colorectal cancer patients: a meta analysis. BMC Cancer. 2019. Volume 19, Article number: 123.
Review
For citations:
Raskin G.A., Ivanova A.K., Mukhina M.S., Orlova R.V. Pathological and molecular features of liver metastases of colon adenocarcinoma. Annaly khirurgicheskoy gepatologii = Annals of HPB Surgery. 2019;24(4):12-17. (In Russ.) https://doi.org/10.16931/1995-5464.2019412-17
Views:
654
Email this article 