Skip to main content
Top
Published in: Targeted Oncology 2/2014

01-06-2014 | Original Research

Is availability of anti-EGFR therapy for the colorectal adenocarcinomas showing fascin expression limited?

Authors: Nazım Emrah Koçer, Fazilet Kayaselçuk

Published in: Targeted Oncology | Issue 2/2014

Login to get access

Abstract

Colorectal adenocarcinoma (CRC) is a major cause of death. Fascin expression in CRCs was proved to be related with higher metastatic rates and poor prognosis, while metastatic patients with only wild type K-RAS gene are the candidates of recent molecularly targeted anti-epidermal growth factor receptor (EGFR) therapies. This study is designed to investigate the correlation between the fascin expression status and the K-RAS mutational status of CRCs in order to assess the availability rate of anti-EGFR therapies for patients with fascin-expressing CRCs. Immunohistochemical expression of fascin and mutational status of K-RAS were investigated in the archival materials of randomly selected 50 metastatic colorectal carcinoma patients. Strength of fascin expression and tumor percentage stained with fascin were scored semi quantitatively. c.34 > C (p.G12R), c.35 g > C (p.G12C), c.34G > A (p.G12S), c.35G > A (p.G12D), c.35G > T (p.G12V), c.35G > C (p.G12A), and c.38G > A (p.G13.D) mutations in K-RAS gene were studied by using RT-PCR. In immunohistochemical evaluation, 32 of the 50 cases stained positive with fascin, while 21 were positive for K-RAS mutations in codon 12 (10 patients) or in codon 13 (3 patients). The correlation between the positivity of fascin and the presence of K-RAS mutations, the strength of fascin staining and the presence of K-RAS mutations, and the tumor cell percentage stained with fascin and the presence of K-RAS mutations were found statistically significant. The results of this study suggest that patients with fascin-expressing CRCs have a greater tendency to carry an activating K-RAS mutation which will prevent them from taking targeted anti-EGFR therapies. Larger series are needed to confirm these results.
Literature
3.
go back to reference Hashimoto Y, Kim DJ, Adams JC (2011) The roles of fascins in health and disease. J Pathol 224(3):289–300PubMedCrossRef Hashimoto Y, Kim DJ, Adams JC (2011) The roles of fascins in health and disease. J Pathol 224(3):289–300PubMedCrossRef
4.
go back to reference Hashimoto Y, Skacel M, Lavery IC et al (2006) Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas. BMC Cancer 6:241PubMedCentralPubMedCrossRef Hashimoto Y, Skacel M, Lavery IC et al (2006) Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas. BMC Cancer 6:241PubMedCentralPubMedCrossRef
5.
go back to reference Oh SY, Kim YB, Suh KW et al (2012) Prognostic impact of fascin-1 expression is more significant in advanced colorectal cancer. J Surg Res 172(1):102–108PubMedCrossRef Oh SY, Kim YB, Suh KW et al (2012) Prognostic impact of fascin-1 expression is more significant in advanced colorectal cancer. J Surg Res 172(1):102–108PubMedCrossRef
6.
go back to reference Puppa G, Maisonneuve P, Sonzogni A et al (2007) Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma. Br J Cancer 96(7):1118–1126PubMedCentralPubMedCrossRef Puppa G, Maisonneuve P, Sonzogni A et al (2007) Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma. Br J Cancer 96(7):1118–1126PubMedCentralPubMedCrossRef
7.
go back to reference El Zouhairi M, Charabaty A, Pishvaian MJ (2011) Molecularly targeted therapy for metastatic colon cancer: proven treatments and promising new agents. Gastrointest Cancer Res 4(1):15–21PubMedCentralPubMed El Zouhairi M, Charabaty A, Pishvaian MJ (2011) Molecularly targeted therapy for metastatic colon cancer: proven treatments and promising new agents. Gastrointest Cancer Res 4(1):15–21PubMedCentralPubMed
8.
go back to reference van Krieken JH, Jung A, Kirchner T et al (2008) KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch 453(5):417–431PubMedCrossRef van Krieken JH, Jung A, Kirchner T et al (2008) KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchows Arch 453(5):417–431PubMedCrossRef
9.
go back to reference Heinemann V, Stintzing S, Kirchner T (2009) Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR. Cancer Treat Rev 35(3):262–271PubMedCrossRef Heinemann V, Stintzing S, Kirchner T (2009) Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR. Cancer Treat Rev 35(3):262–271PubMedCrossRef
10.
go back to reference Chan C, Jankova L, Fung CL et al (2010) Fascin expression predicts survival after potentially curative resection of node-positive colon cancer. Am J Surg Pathol 34(5):656–666PubMed Chan C, Jankova L, Fung CL et al (2010) Fascin expression predicts survival after potentially curative resection of node-positive colon cancer. Am J Surg Pathol 34(5):656–666PubMed
11.
go back to reference Kureishy N, Sapountzi V, Prag S et al (2002) Fascins and their roles in cell structure and function. Bioessays 24(4):350–361PubMedCrossRef Kureishy N, Sapountzi V, Prag S et al (2002) Fascins and their roles in cell structure and function. Bioessays 24(4):350–361PubMedCrossRef
12.
go back to reference Jawhari AU, Buda A, Jenkins M et al (2003) Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. Am J Pathol 162(1):69–80PubMedCentralPubMedCrossRef Jawhari AU, Buda A, Jenkins M et al (2003) Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro. Am J Pathol 162(1):69–80PubMedCentralPubMedCrossRef
13.
go back to reference Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21(14):2787–2799PubMedCrossRef Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21(14):2787–2799PubMedCrossRef
14.
go back to reference Baselga J, Arteaga CL (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23(11):2445–2459PubMedCrossRef Baselga J, Arteaga CL (2005) Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 23(11):2445–2459PubMedCrossRef
15.
go back to reference Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354PubMedCrossRef Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354PubMedCrossRef
16.
go back to reference Neumann J, Zeindl-Eberhart E, Kirchner T et al (2009) Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract 205(12):858–862PubMedCrossRef Neumann J, Zeindl-Eberhart E, Kirchner T et al (2009) Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract 205(12):858–862PubMedCrossRef
17.
go back to reference Andreyev HJ, Norman AR, Cunningham D et al (1998) Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study. J Natl Cancer Inst 90(9):675–684PubMedCrossRef Andreyev HJ, Norman AR, Cunningham D et al (1998) Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study. J Natl Cancer Inst 90(9):675–684PubMedCrossRef
18.
go back to reference Dix BR, Robbins P, Soong R et al (1994) The common molecular genetic alterations in Dukes' B and C colorectal carcinomas are not short-term prognostic indicators of survival. Int J Cancer 59(6):747–751PubMedCrossRef Dix BR, Robbins P, Soong R et al (1994) The common molecular genetic alterations in Dukes' B and C colorectal carcinomas are not short-term prognostic indicators of survival. Int J Cancer 59(6):747–751PubMedCrossRef
19.
go back to reference Russo A, Bazan V, Agnese V et al (2005) Prognostic and predictive factors in colorectal cancer: Kirsten Ras in CRC (RASCAL) and TP53CRC collaborative studies. Ann Oncol 16(Suppl 4):iv44–iv49PubMed Russo A, Bazan V, Agnese V et al (2005) Prognostic and predictive factors in colorectal cancer: Kirsten Ras in CRC (RASCAL) and TP53CRC collaborative studies. Ann Oncol 16(Suppl 4):iv44–iv49PubMed
20.
go back to reference Tortola S, Marcuello E, González I et al (1999) p53 and K-ras gene mutations correlate with tumor aggressiveness but are not of routine prognostic value in colorectal cancer. J Clin Oncol 17(5):1375–1381PubMed Tortola S, Marcuello E, González I et al (1999) p53 and K-ras gene mutations correlate with tumor aggressiveness but are not of routine prognostic value in colorectal cancer. J Clin Oncol 17(5):1375–1381PubMed
21.
go back to reference Esteller M, González S, Risques RA et al (2001) K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. J Clin Oncol 19(2):299–304PubMed Esteller M, González S, Risques RA et al (2001) K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. J Clin Oncol 19(2):299–304PubMed
22.
go back to reference Modest DP, Stintzing S, Laubender RP et al (2011) Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status. Anticancer Drugs 22(9):913–918PubMedCrossRef Modest DP, Stintzing S, Laubender RP et al (2011) Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status. Anticancer Drugs 22(9):913–918PubMedCrossRef
23.
go back to reference Bouzourene H, Gervaz P, Cerottini JP et al (2000) p53 and Ki-ras as prognostic factors for Dukes' stage B colorectal cancer. Eur J Cancer 36(8):1008–1015PubMedCrossRef Bouzourene H, Gervaz P, Cerottini JP et al (2000) p53 and Ki-ras as prognostic factors for Dukes' stage B colorectal cancer. Eur J Cancer 36(8):1008–1015PubMedCrossRef
24.
go back to reference Hurwitz HI, Yi J, Ince W et al (2009) The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Oncologist 14(1):22–28PubMedCrossRef Hurwitz HI, Yi J, Ince W et al (2009) The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Oncologist 14(1):22–28PubMedCrossRef
25.
go back to reference Petrowsky H, Sturm I, Graubitz O et al (2001) Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases. Eur J Surg Oncol 27(1):80–87PubMedCrossRef Petrowsky H, Sturm I, Graubitz O et al (2001) Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases. Eur J Surg Oncol 27(1):80–87PubMedCrossRef
Metadata
Title
Is availability of anti-EGFR therapy for the colorectal adenocarcinomas showing fascin expression limited?
Authors
Nazım Emrah Koçer
Fazilet Kayaselçuk
Publication date
01-06-2014
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 2/2014
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-013-0275-8

Other articles of this Issue 2/2014

Targeted Oncology 2/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine