PTK (protein Tyrosine Kinase)-6 and HER2 and 4, but Not HER1 and 3 Predict Long-term Survival in Breast Carcinomas

Overview

Journal Br J Cancer

Specialty Oncology

Date 2007 Feb 15

PMID 17299391

Citations 44

Authors

M Aubele

G Auer

A K Walch

A Munro

M J Atkinson

H Braselmann

T Fornander

J M S Bartlett

Affiliations

Soon will be listed here.

Abstract

The HER receptors are of therapeutic and prognostic significance in breast cancer, and their function is modulated by cytoplasmic tyrosine kinases like PTK6 (brk). We performed a retrospective study on archival breast cancer samples from patients with long follow-up and compared the protein expression between individual HERs and between HERs and the PTK6. Univariate and multivariate analyses were used to study the prognostic value of parameters. Metastases-free survival of patients for longer than 240 months was inversely associated (P< or =0.05) with nodal status, tumour size, and oestrogen receptor status, but was also directly associated with high protein expression levels of HER4 and PTK6 in Kaplan-Meier analysis. In multivariate analysis for metastases-free survival of >240 months, the stepwise selected parameters were tumour size (relative risk 3.1), PTK6 expression (0.4), and number of positive lymph nodes (1.2). Furthermore, we demonstrated a timedependence of the prognostic value attributed to the parameters. The HER receptors (HER2,4), but not PTK6, were independent prognostic markers for metastases-free survival at 60 months, whereas at 240 months PTK6 is the strongest prognostic marker. We demonstrate that PTK6 is a prognostic marker of metastases-free survival in breast cancer, and is independent of the classical morphological and molecular markers of lymph node involvement, tumour size, and HER2 status.

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References

Aubele M, Auer G, Voss A, Falkmer U, Rutquist L, Hofler H . Different risk groups in node-negative breast cancer: prognostic value of cytophotometrically assessed DNA, morphometry and texture. Int J Cancer. 1995; 63(1):7-12. DOI: 10.1002/ijc.2910630103. View

Alimandi M, Romano A, Curia M, Muraro R, Fedi P, Aaronson S . Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene. 1995; 10(9):1813-21. View

Barker K, Jackson L, Crompton M . BRK tyrosine kinase expression in a high proportion of human breast carcinomas. Oncogene. 1997; 15(7):799-805. DOI: 10.1038/sj.onc.1201241. View

Llor X, Serfas M, Bie W, Vasioukhin V, Polonskaia M, Derry J . BRK/Sik expression in the gastrointestinal tract and in colon tumors. Clin Cancer Res. 1999; 5(7):1767-77. View

Chen H, Shen C, Tsai Y, Lin F, Huang Y, Chen R . Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin. Mol Cell Biol. 2004; 24(24):10558-72. PMC: 533963. DOI: 10.1128/MCB.24.24.10558-10572.2004. View

Haegebarth A, Heap D, Bie W, Derry J, Richard S, Tyner A . The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-binding activities of the Sam68-like mammalian proteins SLM-1 and SLM-2. J Biol Chem. 2004; 279(52):54398-404. DOI: 10.1074/jbc.M409579200. View

Zhang P, Ostrander J, Faivre E, Olsen A, Fitzsimmons D, Lange C . Regulated association of protein kinase B/Akt with breast tumor kinase. J Biol Chem. 2004; 280(3):1982-91. DOI: 10.1074/jbc.M412038200. View

DiGiovanna M, Stern D, Edgerton S, Whalen S, Moore 2nd D, Thor A . Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients. J Clin Oncol. 2005; 23(6):1152-60. DOI: 10.1200/JCO.2005.09.055. View

Born M, Quintanilla-Fend L, Braselmann H, Reich U, Richter M, Hutzler P . Simultaneous over-expression of the Her2/neu and PTK6 tyrosine kinases in archival invasive ductal breast carcinomas. J Pathol. 2005; 205(5):592-6. DOI: 10.1002/path.1720. View

10.

Wiseman S, Makretsov N, Nielsen T, Gilks B, Yorida E, Cheang M . Coexpression of the type 1 growth factor receptor family members HER-1, HER-2, and HER-3 has a synergistic negative prognostic effect on breast carcinoma survival. Cancer. 2005; 103(9):1770-7. DOI: 10.1002/cncr.20970. View

11.

Hynes N, Lane H . ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005; 5(5):341-54. DOI: 10.1038/nrc1609. View

12.

Tovey S, Dunne B, Witton C, Forsyth A, Cooke T, Bartlett J . Can molecular markers predict when to implement treatment with aromatase inhibitors in invasive breast cancer?. Clin Cancer Res. 2005; 11(13):4835-42. DOI: 10.1158/1078-0432.CCR-05-0196. View

13.

Haegebarth A, Nunez R, Tyner A . The intracellular tyrosine kinase Brk sensitizes non-transformed cells to inducers of apoptosis. Cell Cycle. 2005; 4(9):1239-46. DOI: 10.4161/cc.4.9.1965. View

14.

Bianchi S, Palli D, Falchetti M, Saieva C, Masala G, Mancini B . ErbB-receptors expression and survival in breast carcinoma: a 15-year follow-up study. J Cell Physiol. 2005; 206(3):702-8. DOI: 10.1002/jcp.20535. View

15.

Jacobs T, Gown A, Yaziji H, Barnes M, Schnitt S . Specificity of HercepTest in determining HER-2/neu status of breast cancers using the United States Food and Drug Administration-approved scoring system. J Clin Oncol. 1999; 17(7):1983-7. DOI: 10.1200/JCO.1999.17.7.1983. View

16.

Kew T, Bell J, Pinder S, Denley H, Srinivasan R, Gullick W . c-erbB-4 protein expression in human breast cancer. Br J Cancer. 2000; 82(6):1163-70. PMC: 2363344. DOI: 10.1054/bjoc.1999.1057. View

17.

Olayioye M, Neve R, Lane H, Hynes N . The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 2000; 19(13):3159-67. PMC: 313958. DOI: 10.1093/emboj/19.13.3159. View

18.

Richter J, Wagner U, Kononen J, Fijan A, Bruderer J, Schmid U . High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer. Am J Pathol. 2000; 157(3):787-94. PMC: 1885698. DOI: 10.1016/s0002-9440(10)64592-0. View

19.

Kamalati T, Jolin H, Fry M, Crompton M . Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation. Oncogene. 2000; 19(48):5471-6. DOI: 10.1038/sj.onc.1203931. View

20.

Mendelsohn J, Baselga J . The EGF receptor family as targets for cancer therapy. Oncogene. 2001; 19(56):6550-65. DOI: 10.1038/sj.onc.1204082. View