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British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Mar;69(3):550–554. doi: 10.1038/bjc.1994.100

Immunoradiometric detection of pS2 and total cathepsin D in primary breast cancer biopsies: their correlation with steroid receptors.

S Marsigliante 1, L Biscozzo 1, M Correale 1, A Paradiso 1, G Leo 1, I Abbate 1, C D Dragone 1, C Storelli 1
PMCID: PMC1968878  PMID: 8123486

Abstract

Commercially available immunoradiometric assays were used for pS2 and total cathepsin D determination in the cytosol fraction obtained from 266 primary breast cancers. We show that pS2 and cathepsin D values were significantly associated (Spearman's rank correlation: P < 0.0001) in tumours from lymph node-positive patients (N+), while such association did not reach significance in tumours taken from patients with negative lymph nodes (N-). Moreover, cathepsin D concentrations in pS2-rich tumours (pS2 above the median value, 5 ng mg-1 protein) were significantly higher (Mann-Whitney-Wilcoxon's rank-sum test: P = 0.00001) than those obtained in the samples expressing less than 5 ng of pS2 per mg of protein. pS2 was also correlated to both the oestrogen receptor (ER) (Spearman's rank correlation: P < 0.0001) and the progesterone receptor (PR) (Spearman's rank correlation: P = 0.022). No significant differences in the expression of pS2 and cathepsin D taken from N+ and N- patients were found. Furthermore, no significant differences in pS2 and cathepsin D expression were obtained by stratifying tumours on the basis of their size (T). pS2 and cathepsin D values obtained in ER-positive/PR-positive tumours did not significantly differ from the values obtained in ER-positive/PR-negative and in ER-negative/PR-positive tumours. We conclude that pS2 could have a role in cathepsin D expression, and that it can be used in the assessment of a functioning oestrogen response machinery in those tumours that express only ER.

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Selected References

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  1. Alanko A., Heinonen E., Scheinin T., Tolppanen E. M., Vihko R. Significance of estrogen and progesterone receptors, disease-free interval, and site of first metastasis on survival of breast cancer patients. Cancer. 1985 Oct 1;56(7):1696–1700. doi: 10.1002/1097-0142(19851001)56:7<1696::aid-cncr2820560738>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  2. Alexieva-Figusch J., Van Putten W. L., Blankenstein M. A., Blonk-Van Der Wijst J., Klijn J. G. The prognostic value and relationships of patient characteristics, estrogen and progestin receptors, and site of relapse in primary breast cancer. Cancer. 1988 Feb 15;61(4):758–768. doi: 10.1002/1097-0142(19880215)61:4<758::aid-cncr2820610421>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  3. Allegra J. C., Lippman M. E., Thompson E. B., Simon R., Barlock A., Green L., Huff K. K., Do H. M., Aitken S. C., Warren R. Estrogen receptor status: an important variable in predicting response to endocrine therapy in metastatic breast cancer. Eur J Cancer. 1980 Mar;16(3):323–331. doi: 10.1016/0014-2964(80)90348-5. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. Brouillet J. P., Theillet C., Maudelonde T., Defrenne A., Simony-Lafontaine J., Sertour J., Pujol H., Jeanteur P., Rochefort H. Cathepsin D assay in primary breast cancer and lymph nodes: relationship with c-myc, c-erb-B-2 and int-2 oncogene amplification and node invasiveness. Eur J Cancer. 1990 Apr;26(4):437–441. doi: 10.1016/0277-5379(90)90012-i. [DOI] [PubMed] [Google Scholar]
  6. Byar D. P., Sears M. E., McGuire W. L. Relationship between estrogen receptor values and clinical data in predicting the response to endocrine therapy for patients with advanced breast cancer. Eur J Cancer. 1979 Mar;15(3):299–310. doi: 10.1016/0014-2964(79)90041-0. [DOI] [PubMed] [Google Scholar]
  7. Cappelletti V., Coradini D., Scanziani E., Benini E., Silvestrini R., Di Fronzo G. Prognostic relevance of pS2 status in association with steroid receptor status and proliferative activity in node-negative breast cancer. Eur J Cancer. 1992;28A(8-9):1315–1318. doi: 10.1016/0959-8049(92)90507-x. [DOI] [PubMed] [Google Scholar]
  8. Cavailles V., Garcia M., Rochefort H. Regulation of cathepsin-D and pS2 gene expression by growth factors in MCF7 human breast cancer cells. Mol Endocrinol. 1989 Mar;3(3):552–558. doi: 10.1210/mend-3-3-552. [DOI] [PubMed] [Google Scholar]
  9. Clark G. M., McGuire W. L., Hubay C. A., Pearson O. H., Marshall J. S. Progesterone receptors as a prognostic factor in Stage II breast cancer. N Engl J Med. 1983 Dec 1;309(22):1343–1347. doi: 10.1056/nejm198312013092240. [DOI] [PubMed] [Google Scholar]
  10. Fisher B., Wickerham D. L., Brown A., Redmond C. K. Breast cancer estrogen and progesterone receptor values: their distribution, degree of concordance, and relation to number of positive axillary nodes. J Clin Oncol. 1983 Jun;1(6):349–358. doi: 10.1200/JCO.1983.1.6.349. [DOI] [PubMed] [Google Scholar]
  11. Foekens J. A., Rio M. C., Seguin P., van Putten W. L., Fauque J., Nap M., Klijn J. G., Chambon P. Prediction of relapse and survival in breast cancer patients by pS2 protein status. Cancer Res. 1990 Jul 1;50(13):3832–3837. [PubMed] [Google Scholar]
  12. Garcia M., Capony F., Derocq D., Simon D., Pau B., Rochefort H. Characterization of monoclonal antibodies to the estrogen-regulated Mr 52,000 glycoprotein and their use in MCF7 cells. Cancer Res. 1985 Feb;45(2):709–716. [PubMed] [Google Scholar]
  13. Goussard J., Lechevrel C., Roussel G., Cren H., Bera O., Sala M. Immunoradiometric assay of pS2 protein in breast cancer cytosols. Clin Chem. 1991 Oct;37(10 Pt 1):1759–1762. [PubMed] [Google Scholar]
  14. Helzlsouer K. J., Gordon G. B., Alberg A. J., Bush T. L., Comstock G. W. Relationship of prediagnostic serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing premenopausal breast cancer. Cancer Res. 1992 Jan 1;52(1):1–4. [PubMed] [Google Scholar]
  15. Henry J. A., McCarthy A. L., Angus B., Westley B. R., May F. E., Nicholson S., Cairns J., Harris A. L., Horne C. H. Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer. An immunohistochemical study. Cancer. 1990 Jan 15;65(2):265–271. doi: 10.1002/1097-0142(19900115)65:2<265::aid-cncr2820650214>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  16. Henry J. A., Piggott N. H., Mallick U. K., Nicholson S., Farndon J. R., Westley B. R., May F. E. pNR-2/pS2 immunohistochemical staining in breast cancer: correlation with prognostic factors and endocrine response. Br J Cancer. 1991 Apr;63(4):615–622. doi: 10.1038/bjc.1991.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Horwitz K. B., McGuire W. L. Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. J Biol Chem. 1978 Apr 10;253(7):2223–2228. [PubMed] [Google Scholar]
  18. Horwitz K. B., McGuire W. L. Predicting response to endocrine therapy in human breast cancer: a hypothesis. Science. 1975 Aug 29;189(4204):726–727. doi: 10.1126/science.168640. [DOI] [PubMed] [Google Scholar]
  19. Johnson M. D., Torri J. A., Lippman M. E., Dickson R. B. The role of cathepsin D in the invasiveness of human breast cancer cells. Cancer Res. 1993 Feb 15;53(4):873–877. [PubMed] [Google Scholar]
  20. Koerner F. C., Goldberg D. E., Edgerton S. M., Schwartz L. H. pS2 protein and steroid hormone receptors in invasive breast carcinomas. Int J Cancer. 1992 Sep 9;52(2):183–188. doi: 10.1002/ijc.2910520205. [DOI] [PubMed] [Google Scholar]
  21. Marsigliante S., Biscozzo L., Greco S., Leo G., Storelli C. Relation of cathepsin D level to the estrogen receptor in human breast cancer. Int J Clin Lab Res. 1992;22(1):52–57. doi: 10.1007/BF02591395. [DOI] [PubMed] [Google Scholar]
  22. Masiakowski P., Breathnach R., Bloch J., Gannon F., Krust A., Chambon P. Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res. 1982 Dec 20;10(24):7895–7903. doi: 10.1093/nar/10.24.7895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mathieu M., Rochefort H., Barenton B., Prebois C., Vignon F. Interactions of cathepsin-D and insulin-like growth factor-II (IGF-II) on the IGF-II/mannose-6-phosphate receptor in human breast cancer cells and possible consequences on mitogenic activity of IGF-II. Mol Endocrinol. 1990 Sep;4(9):1327–1335. doi: 10.1210/mend-4-9-1327. [DOI] [PubMed] [Google Scholar]
  24. Parl F. F., Schmidt B. P., Dupont W. D., Wagner R. K. Prognostic significance of estrogen receptor status in breast cancer in relation to tumor stage, axillary node metastasis, and histopathologic grading. Cancer. 1984 Nov 15;54(10):2237–2242. doi: 10.1002/1097-0142(19841115)54:10<2237::aid-cncr2820541029>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  25. Predine J., Spyratos F., Prud'homme J. F., Andrieu C., Hacene K., Brunet M., Pallud C., Milgrom E. Enzyme-linked immunosorbent assay of pS2 in breast cancers, benign tumors, and normal breast tissues. Correlation with prognosis and adjuvant hormone therapy. Cancer. 1992 Apr 15;69(8):2116–2123. doi: 10.1002/1097-0142(19920415)69:8<2116::aid-cncr2820690818>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  26. Ravdin P. M. Evaluation of cathepsin D as a prognostic factor in breast cancer. Breast Cancer Res Treat. 1993;24(3):219–226. doi: 10.1007/BF01833262. [DOI] [PubMed] [Google Scholar]
  27. Ravdin P. M. Evaluation of cathepsin D as a prognostic factor in breast cancer. Breast Cancer Res Treat. 1993;24(3):219–226. doi: 10.1007/BF01833262. [DOI] [PubMed] [Google Scholar]
  28. Rio M. C., Bellocq J. P., Daniel J. Y., Tomasetto C., Lathe R., Chenard M. P., Batzenschlager A., Chambon P. Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa. Science. 1988 Aug 5;241(4866):705–708. doi: 10.1126/science.3041593. [DOI] [PubMed] [Google Scholar]
  29. Rio M. C., Bellocq J. P., Gairard B., Rasmussen U. B., Krust A., Koehl C., Calderoli H., Schiff V., Renaud R., Chambon P. Specific expression of the pS2 gene in subclasses of breast cancers in comparison with expression of the estrogen and progesterone receptors and the oncogene ERBB2. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9243–9247. doi: 10.1073/pnas.84.24.9243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rio M. C., Lepage P., Diemunsch P., Roitsch C., Chambon P. Structure primaire de la protéine humaine pS2. C R Acad Sci III. 1988;307(19):825–831. [PubMed] [Google Scholar]
  31. Rochefort H., Capony F., Garcia M., Cavaillès V., Freiss G., Chambon M., Morisset M., Vignon F. Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? J Cell Biochem. 1987 Sep;35(1):17–29. doi: 10.1002/jcb.240350103. [DOI] [PubMed] [Google Scholar]
  32. Rochefort H. Cathepsin D in breast cancer: a tissue marker associated with metastasis. Eur J Cancer. 1992;28A(11):1780–1783. doi: 10.1016/0959-8049(92)90003-k. [DOI] [PubMed] [Google Scholar]
  33. Rusconi S., Yamamoto K. R. Functional dissection of the hormone and DNA binding activities of the glucocorticoid receptor. EMBO J. 1987 May;6(5):1309–1315. doi: 10.1002/j.1460-2075.1987.tb02369.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sarrif A. M., Durant J. R. Evidence that estrogen-receptor-negative, progesterone-receptor-positive breast and ovarian carcinomas contain estrogen receptor. Cancer. 1981 Sep 1;48(5):1215–1220. doi: 10.1002/1097-0142(19810901)48:5<1215::aid-cncr2820480527>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  35. Schwartz L. H., Koerner F. C., Edgerton S. M., Sawicka J. M., Rio M. C., Bellocq J. P., Chambon P., Thor A. D. pS2 expression and response to hormonal therapy in patients with advanced breast cancer. Cancer Res. 1991 Jan 15;51(2):624–628. [PubMed] [Google Scholar]
  36. Spyratos F., Maudelonde T., Brouillet J. P., Brunet M., Defrenne A., Andrieu C., Hacene K., Desplaces A., Rouëssé J., Rochefort H. Cathepsin D: an independent prognostic factor for metastasis of breast cancer. Lancet. 1989 Nov 11;2(8672):1115–1118. doi: 10.1016/s0140-6736(89)91487-6. [DOI] [PubMed] [Google Scholar]
  37. Tandon A. K., Clark G. M., Chamness G. C., Chirgwin J. M., McGuire W. L. Cathepsin D and prognosis in breast cancer. N Engl J Med. 1990 Feb 1;322(5):297–302. doi: 10.1056/NEJM199002013220504. [DOI] [PubMed] [Google Scholar]
  38. Thorpe S. M., Rochefort H., Garcia M., Freiss G., Christensen I. J., Khalaf S., Paolucci F., Pau B., Rasmussen B. B., Rose C. Association between high concentrations of Mr 52,000 cathepsin D and poor prognosis in primary human breast cancer. Cancer Res. 1989 Nov 1;49(21):6008–6014. [PubMed] [Google Scholar]
  39. Westley B., Rochefort H. A secreted glycoprotein induced by estrogen in human breast cancer cell lines. Cell. 1980 Jun;20(2):353–362. doi: 10.1016/0092-8674(80)90621-2. [DOI] [PubMed] [Google Scholar]

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