The cytosolic levels of pS2, an estrogen-regulated protein, were measured in 100 cases of primary breast cancer and related to several conventional histological and biochemical prognostic factors. The data were statistically analyzed on the basis of two different cutoff points for pS2: 4 and 11 ng/mg of cytosolic proteins. pS2 positivity (cutoff 11 ng/mg) was shown to be associated with smaller tumor size (p = 0.05), a higher differentiation grade (p = 0.007) and a smaller number of mitoses (p = 0.004), but not with menopausal status, lymph node involvement, cathepsin D levels, or proliferative activity determined by the monoclonal antibody Ki67. With the cutoff of 4 ng/mg, the statistical significance was confirmed only for the number of mitoses (p = 0.03), which was also the most closely related covariate in multivariate analysis (p = 0.008). As regards steroid receptor status, a significant difference was observed between pS2+ and pS2– cases (Chi-square = 8.9; p - 0.04, cutoff 4 ng/mg). In conclusion, pS2 positivity, being preferentially expressed in hormone-dependent cells and related to other well-known positive markers, may either indicate a good prognosis or predict responsiveness to endocrine treatment.
EdwardsD.P., ChamnessG.C., Mc GuireW.L.Estrogen and progesterone receptors in breast cancer.Biochem Biophys Acta1979; 560: 457–86.
2.
MasiakowskiP., BreathnachR., BlochJ., GannoF., KrustA., ChambonP.Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line.Nucleic Acids Res1982; 79: 7895–903.
3.
RioM.C., BellocqJ.P., DanielJ.Y.Breast cancer associated pS2 protein: synthesis and secretion by normal stomach mucosa.Science1988; 241: 705–7.
4.
HooseinN.M., ThimL., JorgensenK.H., BrattainM.G.Growth stimulatory effect of pancreatic spasmolytic polypeptide on cultured colon and breast tumor cells.FEBS Lett1989; 247: 303–6.
5.
JakowlewS.B., BreathnachR., Jeltsch, MasiakowskiP., ChambonP.Sequence of PS2 mRNA induced by estrogen in the human breast cancer cell line.Nucleic Acids Res1984; 12: 2861–78.
6.
Prud'hommeJ.F., FridlanskyF., Le CunffM.Cloning of a gene expressed in human breast cancer and regulated by estrogen in MCF-7 cells.DNA1985; 4: 11–21.
7.
PiggottN.H., HenryJ.A., MayF.E.B., WestleyB.R.Antipeptide antibodies against the pNR2 oestrogen regulated protein of human breast cancer cells and detection of pNR2 expression in normal tissues by immunohistochemistry.J Pathol1991; 163: 95–104.
8.
RioM.C., BellocqJ.P., GairardB.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 Sci1987; 84: 9243–7.
9.
PredineJ., SpyratosF., Prud'hommeJ.F.Enzymelinked immunosorbent assay of pS2 in breast cancers, benign tumors, and normal breast tissues.Cancer1992; 69: 2116–23.
10.
BloomH.J.G., RichardsonW.W.Histological grading and prognosis in breast cancer.Br J Cancer1957; 11: 359–77.
11.
EORTC Breast Cancer Cooperative Group. Revision of the standards for the assessment of hormone receptors in human breast cancer.Eur J Cancer1980; 16: 1513–5.
12.
FoekensJ.A., RioM.C., SeguinP.Prediction of relapse and survival in breast cancer patients by pS2 protein status.Cancer Res1990; 50: 3832–7.
13.
GionM., MioneR., PappagalloG.L.pS2 in breast cancer - alternative or complementary tool to steroid receptor status? Evaluation of 446 cases.Brit J Cancer1993; 68: 374–9.
14.
HahnelE., RobbinsP., HarveyJ., SterrettG., HahnelR.Expression of the pS2 gene in breast tissues assessed by pS2-mRNA analysis and pS2-protein radioimmunoassay.Breast Cancer Res Treat1992; 24: 71–4.
15.
BradfordM.A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem1976; 72: 248–54.
16.
GerdesJ., SchwabU., LemkeH., SteinH.Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation.Int J Cancer1983; 31: 13–20.
17.
ClarkG.M., DressierL.G., OwensM.O.Prediction of relapse and survival in patients with node-negative breast cancer by DNA flow cytometry.N Engl J Med1989; 10: 627–33.
18.
KlijnJ.G.M., BernsPmjj, BontenbalM., Alexieva-FigushJ., FoekensJ.A.Clinical breast cancer, new developments in selection and endocrine treatment of patients.J Steroid Biochem Molec Biol1992; 43: 211–21.
19.
HenryJ.A., NicholsonS., HennessyC.Expression of the estrogen regulated pNR-2 mRNA in human breast cancer: relation to estrogen receptor mRNA levels and response to tamoxifen therapy.Br J Cancer1989; 61: 32–8.
20.
HenryJ.A., PiggottN.H., MallickU.K.PNR-2/pS2 immunoistochemical staining in breast cancer: correlation with prognostic factors and endocrine response.Br J Cancer1991; 63: 615–22.
21.
SchwartzL.H., KoernerF.C., EdgertonS.M.pS2 expression and response to hormonal therapy in patients with advanced breast cancer.Cancer Res1991; 51: 624–8.
22.
KlijnJ.G.M., BernsPmjj, Van PattenW.L.J.The prognostic value of oncogene amplification and of tumoral secretory proteins with respect to response to endocrine and chemotherapy in metastatic breast cancer. Proceedings of the American Society of Clinical Oncology, San Diego, CA, 17-19 May 1992.
23.
ThorA.D., KoernerF.C., EdgertonS.M., WoodW.C., StracherM.A., SchwartzL.H.pS2 expression in primary breast carcinomas: relationship to clinical and histological features and survival.Breast Cancer Res Treat1992; 21: 111–9.
24.
GoussardJ., LechevrelG., RousselG., CrenH., BreraO., SalaM.Immunoradiometric assay of pS2 protein in breast cancer cytosols.Clin Chem1991; 37: 1759–62.
25.
FoekensJ.A., Van PuttenW.L.J., PortengenH.Prognostic value of pS2 and Cathepsin D in 710 human primary breast tumours: multivariate analysis.J Clin Oncol1993; 11: 899–908.
26.
CappellettiV., CoradiniD., ScanzianiE., BeniniE., SilvestriniR., Di FronzoG.Prognostic relevance of pS2 status in association with steroid receptor status and proliferative activity in node-negative breast cancer.Eur J Cancer1992; 28A: 1315–8.
27.
ThompsonA.M., HawkinsR.A., EltonR.A., SteelC.M., ChettyU.pS2 is an independent factor of good prognosis in primary breast cancer.Br J Cancer1993; 68: 93–6.
28.
KoernerF.C., GoldbergD.E., EdgertonS.M., SchwartzL.H.pS2 protein and steroid hormone receptors in invasive breast carcinomas.Int J Cancer1992; 52: 183–8.
29.
SkiltonR.A., LuqmaniY.A., McLellandR.A., CoombesR.C.Characterization of a messenger RNA selectively expressed in human breast cancer.Brit J Cancer1989; 60: 168–75.
30.
DelvenneC.G., Winkler-GolR.A., PiccartM.J.Expression of c-erbB2, TGF-betal and pS2 genes in primary human breast cancers.Eur J Cancer1992; 28: 700–5.
31.
RosenP.P., Menendez-BotetC.J., SenieR.T., SchwartzM.K., SchottenfeldD., FarrG.H.Estrogen receptor protein (ERP) and the histopathology of human mammary carcinoma. In: McGuireW.L. ed. Hormones, receptors and breast cancer.New York: Raven Press, 1978; 71.
32.
CavaillesV., GarciaM., RochefortH.Regulation of Cathepsin-D and pS2 gene expression by growth factors in MCF-7 human breast cancer cells.Mol Endocrinol1989; 3: 552–8.
33.
RioM.C., ChambonP.The pS2 gene, mRNA and protein: a potential marker for human breast cancer.Cancer Cells1990; 2: 269–74.
34.
ElledgeR.M., CioccaD.R., LangoneG., McGuireW.L.Estrogen receptor, progesterone receptor and HER-2/neu protein in breast cancers from pregnant patients.Cancer1993; 71: 2499–506.
35.
LuqmaniY.A., RickettsD., RyallG., TurnbullL., LawM., CoombesR.C.Prediction of response to endocrine therapy in breast cancer using immunocytochemical assays for pS2, estrogen receptor and progesterone receptor.Int J Cancer1993; 54: 619–23.
