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Increased phosphotyrosine in breast cancer tissue is associated with a worse prognosis


We have previously demonstrated that phosphotyrosine can be identified in breast cancer cells using an immunohistochemical stain. We have subsequently used this technique to characterize 106 women with breast cancer (46 with Stage 1 and 60 with Stage 2) who have been followed for at least four years by one oncologist. We analyzed all primary breast cancer tissue using immunohistochemical staining and the amount of phosphotyrosine (PT) was scored on a 0 to 3 range. The PT score of the primary tumor was unrelated to either breast cancer stage or estrogen and progesterone receptor analysis, as high PT scores were noted in both disease stages and all receptor categories. We did find that patients with either no or trace (1+) amounts of PT survived longer than those patients with higher amounts of PT. The patients with low PT had significantly lower chance of relapse (Chi Square = 15.8, p < 0.001) and a lower mortality (Chi Square = 13.1, p = 0.001). We conclude that immunohistochemical methods to determine the PT score may identify patients at higher risk for disease relapse independent of tumor stage or hormonal status.

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  1. 1.

    Henderson IC: Adjuvant systemic chemotherapy for early stage breast cancer. Curr Probl Cancer 11: 125–207, 1987

  2. 2.

    McGuire WL, Tandon AK, Allred DC, Chamness GC, Ravdin PM, Clark GM: Prognosis and treatment decisions in patients with breast cancer without axillary node involvement. Cancer 70: 1775–1781, 1992

  3. 3.

    Gasparini G, Pozza F, Harris AL: Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients. J Natl Cancer Inst 85: 1206–1219, 1993

  4. 4.

    Jallal B, Schlessinger J, Ullrich A: Tyrosine phosphatase inhibition permits analysis of signal transduction complexes in p185HER2/neu-overexpressing human tumor cells. J Biol Chem 267: 4357–4363, 1992

  5. 5.

    Hunter T, Cooper JA: Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells. Cell 24: 741–745, 1981

  6. 6.

    Heldin CH, Westermark B: Growth factors: mechanism of action and relation to oncogenes. Cell 37: 9–15, 1984

  7. 7.

    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 35: 177–182, 1987

  8. 8.

    Tandon AK, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 7: 110–118, 1989

  9. 9.

    Sainsbury JRC, Farndon JK, Needham GK, Malcolm AJ, Harris AL: Epidermal growth factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1: 1398–1402, 1987

  10. 10.

    Dickson RB, Johnson MD, Baino M, Shi E, Kurebayashi J, Ziff B, Martinez-Lacaci I, Amundadohir LT, Lippman ME: Growth factors in breast cancer: mitogenesis to transformation. J Steroid Biochem Molec Biol 43: 69–78, 1992

  11. 11.

    Hennipman A, van Oirschot A, Smits J, Rijksen G, Staal GEF: Tyrosine kinase activity in breast cancer, benign breast disease, and normal breast tissue. Cancer Res 49: 516–521, 1989

  12. 12.

    Durocher Y, Chevlier S: Protein tyrosine kinases in human breast cancer: kinetic properties and evidence for the presence of two forms of native enzyme. Breast Cancer Res Treat 17: 99–107, 1990

  13. 13.

    Lower EE, Franco RS, Miller MA, Martelo OJ: Enzymatic and immunohistochemical evaluation of tyrosine phosphorylation in breast cancer specimens. Breast Cancer Res Treat 26: 217–224, 1993

  14. 14.

    Beahrs OH, Henson DE, Hutter RP, Myers MH: American Joint Commission on Cancer: Manual for Staging of Cancer. 3rd ed. Philadelphia: J B Lippincott; 145, 1988

  15. 15.

    Fisher B, Redmond C, Brown Aet al.: Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer. J Clin Oncol 1: 227–241, 1983

  16. 16.

    Pavelic K, Pavelic ZP, Denton D, Reising J, Khalily M, Preisler HD: Immunohistochemical detection of c-myc oncoprotein in paraffin-embedded tissues. J Exp Pathol 5: 143–153, 1990

  17. 17.

    Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481, 1958

  18. 18.

    Thor AD, Moore DH, Edgerton SM: Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst 84: 845–855, 1992

  19. 19.

    McGuire WL, Clark GW: Prognostic factors and treatment decisions in axillary node-negative breast cancer. N Engl J Med 326: 1756–1761, 1992

  20. 20.

    Ottenhoff-Kaiff AE, Rijksen G, van Beurden EACM, Hennipman A, Michels AA, Staal GEJ: Characterization of protein tyrosine kinases from human breast cancer: involvement of the c-src oncogene product. Cancer Res 52: 4773–4778, 1992

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Correspondence to Elyse E. Lower.

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Lower, E.E., Miller, M.A., Williams, L. et al. Increased phosphotyrosine in breast cancer tissue is associated with a worse prognosis. Breast Cancer Res Tr 35, 277–282 (1995).

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Key words

  • phosphotyrosine content
  • immunohistochemistry
  • tyrosine kinase
  • survival
  • prognosis