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Prognostic evaluation of oestrogen-regulated protein immunoreactivity in ductal invasive (NOS) breast cancer

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Abstract

Determination of steroid receptors and several oestrogen-regulated proteins in mammary carcinomas is useful in the prediction of their evolution and of the likely success of endocrine therapy. Cathepsin D (Cat D), pS2 peptide and heat shock protein 27 (Hsp 27) were detected immunohistochemically in 63 infiltrating ductal (NOS) breast carcinomas, and our results were qualitatively correlated with several clinicopathological indicators and patients' overall survival. Cat D immunostaining of tumour cells was strongly associated with axillary nodal involvement (P f=0.0005) and so, it is directly connected with the metastatic capacity of malignant cells. pS2 immunoreactivity was correlated with oestrogen and progesterone receptor positivity (P f=0.0009 and P f=0.05 respectively) and, nonsignificantly, with good differentiation of the tumours (P f=0.06). Neoplastic cells expressing this protein are therefore characterised by a highly organised state of cellular physiology. Hsp 27 was expressed predominantly in tumours with one to four infiltrated lymph nodes (P t=0.05), and Hsp 27-positive patients were inclined to rather short survival, possibly due to chemotherapy resistance. In future, prognostic estimation of each one of the examined markers should be performed in specific large subgroups of patients. The findings of this study contribute to the establishment of criteria by which these subgroups should be formed.

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References

  1. Bloom HCJ, Richardson WW (1957) Histological grading and prognosis of breast cancer. Br J Cancer 11:359–377

    Google Scholar 

  2. Cappelletti V, Cordini D, Scanziani E, Benini E, Silvestrini R, Di Fronzo G (1992) Prognostic revelance of pS2 status in association with steroid receptor status and proliferative activity in node-negative breast cancer. Eur J Cancer 28A:1315–1318

    Google Scholar 

  3. Ciocca DR, Fuqua SAW, Lock-Lim S, Toft DO, Welch WJ, McGuire WL (1992) Response of human breast cancer cells to heat shock and chemotherapeutic drugs. Cancer Res 52:3648–3654

    Google Scholar 

  4. Ciocca DR, Oesterreich S, Chamness GC, McGuire WL, Fuqua SAW (1993) Biological and clinical implications of heat shock protein 27000 (Hsp 27): a review. J Natl Cancer Inst 85:12558–12570

    Google Scholar 

  5. Coopman P, Garcia M, Brunner N, Deroco D, Clarke R, Rochefort H (1994) Anti-proliferative and anti-estrogenic effects of ICI 164,384 and ICI 182,780 in 4-OH-tamoxifen-resistant human breast-cancer cells. Int J Cancer 56:295–300

    Google Scholar 

  6. Dookeran KA, Rye PD, Dearing SJ, Walker RA (1993) Expression of the pS2 peptide in primary breast carcinomas: comparison of membrane and cytoplasmic staining patterns. J Pathol 171:123–129

    Google Scholar 

  7. Edwards DP, Estes PA, Fadok VA, Bona BJ, Onate S, Nordeen SK, Welch WJ (1992) Heat shock alters the composition of heteromeric steroid receptor complexes and enhances receptor activity in vivo. Biochemistry 31:2482–2491

    Google Scholar 

  8. Figueroa JA, Yee D, McGuire WL (1993) Prognostic indicators in early breast cancer. Am J Med Sci 305:176–182

    Google Scholar 

  9. Foekens JA, Rio M-C, Seguin P, Van Putten WLJ, Fauque J, Nap M, Klijn JGM, Chambon P (1990) Prediction of relapse and survival in breast cancer patients by pS2 protein status. Cancer Res 50:3832–3837

    Google Scholar 

  10. Gion M, Mione R, Pappagallo GL, Gatti C, Nascimben O, Bari M, Leon AE, Vinante O, Bruscagnin G (1993) PS2 in breast cancer: alternative or complementary tool to steroid receptor status? Evaluation of 446 cases. Br J Cancer 68:374–379

    Google Scholar 

  11. Hahnel R, Harvey J, Robbins P, Sterrett G (1993) Cathepsin-D in human breast cancer: correlation with vascular invasion and other clinical and histopathological characteristics. Anticancer Res 13:2131–2136

    Google Scholar 

  12. Johnson MD, Torri JA, Lippman ME, Dickson RB (1993) The role of Cathepsin-D in the invasiveness of human breast cancer cells. Cancer Res 53:873–877

    Google Scholar 

  13. Isola J, Weitz S, Visakarpi T, Holi K, Shea R, Khabbaz N, Kallioniemi O-P (1993) Cathepsin D expression detected by immunohistochemistry has independent prognostic value in axillary node-negative breast cancer. J Clin Oncol 11:36–43

    Google Scholar 

  14. Kandalaft PL, Chang KL, Ahn CW, Traweek ST, Mehta P, Battifora H (1993) Prognostic significance of immunohistochemical analysis of Cathepsin D in low-stage breast cancer. Cancer 71:2756–2763

    Google Scholar 

  15. Kardas I, Seitz G, Limon J, Niezabitowski A, Rys J, Theisinger B, Welter C, Blin N (1993) Retrospective analysis of prognostic significance of the estrogen-inducible pS2 gene in male breast carcinoma. Cancer 72:1652–1656

    Google Scholar 

  16. Koerner FC, Goldberg DE, Edgerton SM, Schwartz LH (1992) pS2 protein and steroid hormone receptors in invasive breast carcinomas. Int J Cancer 52:183–188

    Google Scholar 

  17. Luqmani Y, Bennett C, Paterson I, Corbishley CM, Rio M-C, Chambon P, Ryall G (1989) Expression of the pS2 gene in normal, benign and neoplastic human stomach. Int J Cancer 44:806–812

    Google Scholar 

  18. Mori K, Fujii R, Kida N, Takahashi H, Ohkudo S, Fujino M, Ohta M, Hayashi K (1990) Complete primary structure of the human estrogen-responsive gene (pS2) product. J Biochem 107:73–76

    Google Scholar 

  19. Oesterreich S, Ciocca DR, Wiebe V, et al (1992) Association between heat shock proteins and drug resistance in human breast cancer cells (abstract). Breast Cancer Treat 23:178

    Google Scholar 

  20. Pallud C, Le Doussal V, Pichon M-F, Prud'Homme J-F, Hacene K, Milgrom E (1993) Immunohistochemistry of pS2 in normal human breast and in various histological forms of breast tumours. Histopathology 23:249–256

    Google Scholar 

  21. Predine J, Spyratos F, Prud'homme JF, et al (1992) Enzyme linked immunosorbent assay (ELISA) of pS2 in breast cancers, benign tumors and normal breast tissues. Correlation with prognosis and adjuvant hormonotherapy. Cancer 69:2116–2123

    Google Scholar 

  22. Pujol P, Maudelonde T, Daures J-P, Rouanet P, Brouillet J-P, Pujol H, Rochefort H (1993) A prospective study of the prognostic value of Cathepsin D levels in breast cancer cytosol. Cancer 71:2006–2012

    Google Scholar 

  23. Rilke F, Colnaghi MI, Cascinelli N, Andreola S, Baldini MT, Bufalino R, Della Porta G, Menard S, Pierotti M, Testori A (1991) Prognostic significance of HER-2/neu expression in breast cancer and its relationship to other prognostic factors. Int J Cancer 49:44–49

    Google Scholar 

  24. Rio M-C, Chambon P (1990) The pS2 gene, mRNA and protein: a potential marker for human breast cancer. Cancer Cells 2:269–274

    Google Scholar 

  25. Schwartz GF, Schwarting R, Rabindranauth P, Finkel GC (1993) Clinical applications of serum and tissue markers in malignant disease: breast cancer as the paradigm. Clin Chem 39:2404–2412

    Google Scholar 

  26. Scorilas A, Yotis J, Gouriotis D, Keramopoulos A, Ampela K, Trangas T, Talieri M (1993) Cathepsin-D and c-erb-B 2 have an additive prognostic value for breast cancer patients. Anticancer Res 13:1895–1900

    Google Scholar 

  27. Storm FK, Mahvi DM, Gilchrist KW (1993) Hsp-27 has no diagnostic or prognostic significance in prostate or bladder cancers. Urol 42:379–381

    Google Scholar 

  28. Tandon AK, Clark GM, Chamness GC, Chirgwin JM, McGuire WL (1990) Cathepsin D and prognosis in breast cancer. N Engl J Med 322:297–302

    Google Scholar 

  29. Thor A, Benz C, Moore D, Goldman E, Edgerton S, Landry J, Mayall B, Schwartz L, Hickey E, Weber LA (1991) Stress response protein (SRP-27) determination in primary human breast carcinomas: clinical, histologic and prognostic correlations. J Natl Cancer Inst 83:170–178

    Google Scholar 

  30. Whelan RD, Hill BT (1993) Differential expression of steroid receptors, Hsp27 and pS2 in a series of drug resistant human breast tumor cell lines derived following exposure to antitumor drugs or to fractionated X-irradiation. Breast Cancer Res Treat 26:23–39

    Google Scholar 

  31. Winstanley JHR, Leinster SJ, Cooke TG, Westley BR, Plat-Higgins AM, Rudland PS (1993) Prognostic significance of cathepsin-D in patients with breast cancer. Br J Cancer 67:767–772

    Google Scholar 

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Nakopoulou, L., Lazaris, A.C., Baltas, D. et al. Prognostic evaluation of oestrogen-regulated protein immunoreactivity in ductal invasive (NOS) breast cancer. Vichows Archiv A Pathol Anat 427, 33–40 (1995). https://doi.org/10.1007/BF00203735

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