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01.04.2010 | Original Article

Epidermal growth factor receptor (EGFR) mRNA levels and protein expression levels in primary colorectal cancer and corresponding liver metastases

verfasst von: Hidekazu Kuramochi, Kazuhiko Hayashi, Go Nakajima, Hirotaka Kamikozuru, Masakazu Yamamoto, Kathleen D. Danenberg, Peter V. Danenberg

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2010

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Abstract

Purpose

High expression levels of EGFR mRNA are reported to be associated with a higher response probability in epidermal growth factor receptor (EGFR) targeted drugs. Our aim was to determine how EGFR gene expression levels in primary colorectal cancer (CRC) were related to those in liver metastases.

Methods

31 pairs of primary CRC and corresponding liver metastases were analyzed. Gene expression level was measured using real-time RT-PCR.

Results

No significant difference was observed between median mRNA expression levels of EGFR in primary cancer and those in corresponding liver metastases (P = 0.99). When matched tissue sets were compared on an individual basis, there was a significant correlation for EGFR mRNA expression between primary cancer and corresponding liver metastases (r _s = 0.78, P < 0.0001).

Conclusions

A good prediction of EGFR mRNA levels in liver metastases can be obtained by measuring those in the primary CRC.

Carpenter G, Cohen S (1990) Epidermal growth factor. J Biol Chem 265:7709–7712PubMed

Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208CrossRefPubMed

Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345CrossRefPubMed

Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664CrossRefPubMed

Adams R, Maughan T (2007) Predicting response to epidermal growth factor receptor-targeted therapy in colorectal cancer. Expert Rev Anticancer Ther 7:503–518CrossRefPubMed

Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, Hamilton A, Pan D, Schrag D, Schwartz L, Klimstra DS, Fridman D, Kelsen DP, Saltz LB (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23:1803–1810CrossRefPubMed

Vallbohmer D, Zhang W, Gordon M, Yang DY, Yun J, Press OA, Rhodes KE, Sherrod AE, Iqbal S, Danenberg KD, Groshen S, Lenz HJ (2005) Molecular determinants of cetuximab efficacy. J Clin Oncol 23:3536–3544CrossRefPubMed

Dziadziuszko R, Witta SE, Cappuzzo F, Park S, Tanaka K, Danenberg PV, Baron AE, Crino L, Franklin WA, Bunn PA Jr, Varella-Garcia M, Danenberg KD, Hirsch FR (2006) Epidermal growth factor receptor messenger RNA expression, gene dosage, and gefitinib sensitivity in non-small cell lung cancer. Clin Cancer Res 12:3078–3084CrossRefPubMed

Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, Wong TW, Huang X, Takimoto CH, Godwin AK, Tan BR, Krishnamurthi SS, Burris HA 3rd, Poplin EA, Hidalgo M, Baselga J, Clark EA, Mauro DJ (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25:3230–3237CrossRefPubMed

10.

Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ (2004) Cancer statistics, 2004. CA Cancer J Clin 54:8–29CrossRefPubMed

11.

Bonner RF, Emmert-Buck M, Cole K, Pohida T, Chuaqui R, Goldstein S, Liotta LA (1997) Laser capture microdissection: molecular analysis of tissue. Science 278:1481–1483CrossRefPubMed

12.

Kuramochi H, Hayashi K, Uchida K, Miyakura S, Shimizu D, Vallbohmer D, Park S, Danenberg KD, Takasaki K, Danenberg PV (2006) 5-fluorouracil-related gene expression levels in primary colorectal cancer and corresponding liver metastasis. Int J Cancer 119:522–526CrossRefPubMed

13.

Lord RV, Salonga D, Danenberg KD, Peters JH, DeMeester TR, Park JM, Johansson J, Skinner KA, Chandrasoma P, DeMeester SR, Bremner CG, Tsai PI, Danenberg PV (2000) Telomerase reverse transcriptase expression is increased early in the Barrett’s metaplasia, dysplasia, adenocarcinoma sequence. J Gastrointest Surg 4:135–142CrossRefPubMed

14.

Gibson UE, Heid CA, Williams PM (1996) A novel method for real time quantitative RT-PCR. Genome Res 6:995–1001CrossRefPubMed

15.

Heid CA, Stevens J, Livak KJ, Williams PM (1996) Real time quantitative PCR. Genome Res 6:986–994CrossRefPubMed

16.

Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Cote JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault-Llorca F, Laurent-Puig P (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66:3992–3995CrossRefPubMed

17.

Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, Bastit L, Killian A, Sesboue R, Tuech JJ, Queuniet AM, Paillot B, Sabourin JC, Michot F, Michel P, Frebourg T (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer 96:1166–1169CrossRefPubMed

18.

Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626–1634CrossRefPubMed

19.

De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, Biesmans B, Van Laethem JL, Peeters M, Humblet Y, Van Cutsem E, Tejpar S (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19:508–515CrossRefPubMed

20.

Lievre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouche O, Landi B, Louvet C, Andre T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F, Laurent-Puig P (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26:374–379CrossRefPubMed

21.

Bos JL, Fearon ER, Hamilton SR, Verlaan-de Vries M, van Boom JH, van der Eb AJ, Vogelstein B (1987) Prevalence of ras gene mutations in human colorectal cancers. Nature 327:293–297CrossRefPubMed

22.

Boughdady IS, Kinsella AR, Haboubi NY, Schofield PF (1992) K-ras gene mutations in adenomas and carcinomas of the colon. Surg Oncol 1:275–282CrossRefPubMed

23.

Finkelstein SD, Sayegh R, Christensen S, Swalsky PA (1993) Genotypic classification of colorectal adenocarcinoma. Biologic behavior correlates with K-ras-2 mutation type. Cancer 71:3827–3838CrossRefPubMed

24.

Kuramochi H, Hayashi K, Uchida K, Miyakura S, Shimizu D, Vallbohmer D, Park S, Danenberg KD, Takasaki K, Danenberg PV (2006) Vascular endothelial growth factor messenger RNA expression level is preserved in liver metastases compared with corresponding primary colorectal cancer. Clin Cancer Res 12:29–33CrossRefPubMed

25.

Maurer CA, Friess H, Kretschmann B, Zimmermann A, Stauffer A, Baer HU, Korc M, Buchler MW (1998) Increased expression of erbB3 in colorectal cancer is associated with concomitant increase in the level of erbB2. Hum Pathol 29:771–777CrossRefPubMed

26.

Piazzi G, Paterini P, Ceccarelli C, Pantaleo MA, Biasco G (2006) Molecular determination of epidermal growth factor receptor in normal and neoplastic colorectal mucosa. Br J Cancer 95:1525–1528CrossRefPubMed

27.

McKay JA, Murray LJ, Curran S, Ross VG, Clark C, Murray GI, Cassidy J, McLeod HL (2002) Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. Eur J Cancer 38:2258–2264CrossRefPubMed

28.

Scartozzi M, Bearzi I, Berardi R, Mandolesi A, Fabris G, Cascinu S (2004) Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. J Clin Oncol 22:4772–4778CrossRefPubMed

29.

Bibeau F, Boissiere-Michot F, Sabourin JC, Gourgou-Bourgade S, Radal M, Penault-Llorca F, Rochaix P, Arnould L, Bralet MP, Azria D, Ychou M (2006) Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray. Virchows Arch 449:281–287CrossRefPubMed

30.

Bralet MP, Paule B, Falissard B, Adam R, Guettier C (2007) Immunohistochemical variability of epidermal growth factor receptor (EGFR) in liver metastases from colonic carcinomas. Histopathology 50:210–216CrossRefPubMed

31.

Yamada M, Ichikawa Y, Yamagishi S, Momiyama N, Ota M, Fujii S, Tanaka K, Togo S, Ohki S, Shimada H (2008) Amphiregulin is a promising prognostic marker for liver metastases of colorectal cancer. Clin Cancer Res 14:2351–2356CrossRefPubMed

32.

Spindler KL, Lindebjerg J, Nielsen JN, Olsen DA, Bisgard C, Brandslund I, Jakobsen A (2006) Epidermal growth factor receptor analyses in colorectal cancer: a comparison of methods. Int J Oncol 29:1159–1165PubMed

33.

Makino H, Uetake H, Danenberg K, Danenberg PV, Sugihara K (2008) Efficacy of laser capture microdissection plus RT-PCR technique in analyzing gene expression levels in human gastric cancer and colon cancer. BMC Cancer 8:210CrossRefPubMed

Titel: Epidermal growth factor receptor (EGFR) mRNA levels and protein expression levels in primary colorectal cancer and corresponding liver metastases
verfasst von: Hidekazu Kuramochi
Kazuhiko Hayashi
Go Nakajima
Hirotaka Kamikozuru
Masakazu Yamamoto
Kathleen D. Danenberg
Peter V. Danenberg
Publikationsdatum: 01.04.2010
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2010
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-1087-5

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Epidermal growth factor receptor (EGFR) mRNA levels and protein expression levels in primary colorectal cancer and corresponding liver metastases