We conducted this study to examine whether the expression of c-erbB-2 and p53 is the prognostic indicator for patients with early-stage breast cancer in which axillary lymph node metastasis is absent. We examined 326 patients with early-stage breast cancer in which axillary lymph node metastasis is absent. Tissue microarrays were constructed. Following this, immunohistochemical staining was done for estrogen receptor (ER), progesterone receptor (PR), c-erbB2, and p53. The results were as follows: (1) expression of c-erbB-2 was correlated with other clinicopathologic factors (eg, patient's age, presence of menopause, tumor size, histologic and nuclear grade, and presence of hormone receptors such as ER and PR); and (2) expression of p53 was correlated with survival rate, patient's age, presence of menopause, and tumor size. However, these results were not statistically significant. In conclusion, our results indicate that expression of c-erbB-2 and p53 did not have any prognostic value in patients with early-stage breast cancer in which axillary lymph node metastasis is absent.
Carter CL, Allen C., Henson DERelation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer.1989;63:181-187.
2.
Lethaby AE, Mason BH, Harvey VJ, Holdaway IMSurvival of women with node negative breast cancer in the Auckland region . N Z Med J. 1996;109:330-333.
3.
Pertschuk LP, Feldman JG, Eisenberg KB, et al. Immunocytochemical detection of progesterone receptor in breast cancer with monoclonal antibody. Relation to biochemical assay, disease-free survival, and clinical endocrine response. Cancer. 1988;62:342-349.
4.
Quenel N., Wafflart J., Bonichon F., et al. The prognostic value of c-erbB2 in primary breast carcinomas: a study on 942 cases. Breast Cancer Res Treat.1995;35:283-291.
5.
Toikkanen S. , Helin H., Isola J., Joensuu H.Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up. J Clin Oncol.1992;10:1044-1048.
6.
Martinazzi M. , Crivelli F., Zampatti C., Martinazzi S.Relationship between p53 expression and other prognostic factors in human breast carcinoma. An immunohistochemical study . Am J Clin Pathol.1993;100: 213-217.
7.
Cowan WK, Kelly P., Sawan A., et al. The pathological and biological nature of screen-detected breast carcinomas: a morphological and immunohistochemical study. J Pathol.1997;182:29-35.
8.
McGuire WLAdjuvant therapy of node-negative breast cancer. N Engl J Med.1989;320:525-527.
9.
Elston CW, Ellis IOPathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up . Histopathology. 1991;19:403-410.
10.
Fitzgibbons PL, Page DL, Weaver D., et al. Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med.2000;124:966-978.
11.
Kononen J., Bubendorf L., Kallioniemi A., et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med.1998;4:844-847.
12.
Nocito A., Kononen J., Kallioniemi OP, Sauter G.Tissue microarrays (TMAs) for high-throughput molecular pathology research . Int J Cancer. 2001;94:1-5.
13.
Pertschuk LP , Feldman JG, Kim YD, et al. Estrogen receptor immunocytochemistry in paraffin embedded tissues with ER1D5 predicts breast cancer endocrine response more accurately than H222Sp gamma in frozen sections or cytosol-based ligand-binding assays. Cancer. 1996;77:2514-2519.
14.
De Potter CR , Quatacker J., Maertens G., et al. The subcellular localization of the neu protein in human normal and neoplastic cells. Int J Cancer.1989;44:969-974.
15.
Styles JM, Harrison S., Gusterson BA, Dean CJRat monoclonal antibodies to the external domain of the product of the C-erbB-2 proto-oncogene. Int J Cancer.1990;45: 320-324.
16.
Marchetti A. , Buttitta F., Pellegrini S., et al. p53 mutations and histological type of invasive breast carcinoma. Cancer Res.1993;53:4665-4669.
17.
Moll UM, Riou G., Levine AJTwo distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion . Proc Natl Acad Sci U S A. 1992;89:7262-7266.
18.
Adami HOBreast cancer incidence and mortality. Aspects on aetiology, time trends and curability. Acta Chir Scand.1984; 519 (suppl):9-14 .
19.
Elledge RM, McGuire WL, Osborne CKPrognostic factors in breast cancer. Semin Oncol.1992;19:244-253.
20.
Early Breast Cancer Trialists' Collaborative Group.Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Lancet. 1992;339:1-15.
21.
Rosen PP, Groshen S., Kinne DWPrognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study. J Clin Oncol.1991;9:1650-1661.
22.
Pereira H., Pinder SE, Sibbering DM, et al. Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma. Histopathology. 1995;27:219-226.
23.
Henson DE, Ries L., Freedman LS, Carriaga M.Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index. Cancer. 1991;68:2142-2149.
24.
Schumacher M., Schmoor C., Sauerbrei W., et al. The prognostic effect of histological tumor grade in node-negative breast cancer patients. Breast Cancer Res Treat.1993;25:235-245.
25.
Galea MH, Blamey RW, Elston CE, Ellis IOThe Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat.1992;22:207-219.
26.
Balslev I., Axelsson CK, Zedeler K., Rasmussen BB, Carstensen B., Mouridsen HTThe Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG). Breast Cancer Res Treat. 1994;32:281-290.
27.
Slamon DJ, Clark GMAmplification of c-erbB-2 and aggressive human breast tumors?Science. 1988;240: 1795-1798.
28.
Albanell J. , Bellmunt J., Molina R., et al. Node-negative breast cancers with p53(-)/HER2-neu(-) status may identify women with very good prognosis. Anticancer Res.1996;16:1027-1032.
29.
Gusterson BA , Gelber RD, Goldhirsch, et al. Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group . J Clin Oncol.1992;10:1049-1056.
30.
Marks JR, Humphrey PA, Wu K., et al. Overexpression of p53 and HER-2/neu proteins as prognostic markers in early stage breast cancer. Ann Surg.1994 ;219:332-341.
31.
Rosen PP, Lesser ML, Arroyo CD, Cranor M., Borgen P., Norton L.Immunohistochemical detection of HER2/ neu in patients with axillary lymph node negative breast carcinoma. A study of epidemiologic risk factors, histologic features, and prognosis. Cancer.1995;75:1320-1326.
32.
Allred DC, Clark GM, Tandon AK, et al. HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol.1992;10:599-605.
33.
Gusterson BA, Machin LG, Gullick WJ, et al. Immunohistochemical distribution of c-erbB-2 in infiltrating and in situ breast cancer. Int J Cancer. 1988 ;42:842-845.
34.
Lovekin C., Ellis IO, Locker A., et al. c-erbB-2 oncoprotein expression in primary and advanced breast cancer. Br J Cancer.1991;63:439-443.
35.
Paik S., Burkhard E., Lippman MEClinical significance of erbB2 protein overexpression. Cancer Treat Res.1992;61:181-191.
36.
Somerville JE, Clarke LA, Biggart JDc-erbB-2 overexpression and histological type of in situ and invasive breast carcinoma. J Clin Pathol.1992;45:16-20.
37.
Gullick WJ, Love SB, Wright C., et al. c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. Br J Cancer.1991;63:434-438.
38.
Horiguchi J. , Iino Y., Takei H., Yokoe T., Ishida T., Morishita Y.Immunohistochemical study on the expression of c-erbB-2 oncoprotein in breast cancer. Oncology. 1994;51: 47-51.
39.
Xing WR, Gilchrist KW, Harris CP, Samson W., Meisner LFFISH detection of HER-2/neu oncogene amplification in early onset breast cancer . Breast Cancer Res Treat.1996; 39:203-212.
40.
Bertheau P. , Steinberg SM, Merino MJC-erbB-2, p53, and nm23 gene product expression in breast cancer in young women: immunohistochemical analysis and clinicopathologic correlation. Hum Pathol.1998;29: 323-329.
41.
Barbati A., Cosmi EV, Sidoni A., et al. Value of c-erbB-2 and p53 oncoprotein co-overexpression in human breast cancer. Anticancer Res.1997;17:401-405.
42.
Bebenek M., Bar JK, Harlozinska A., Sedlaczek P.Prospective studies of p53 and c-erbB-2 expression in relation to clinicopathological parameters of human ductal breast cancer in the second stage of clinical advancement . Anticancer Res.1998;18:619-623.
43.
Nakopoulou LL, Alexiadou A., Theodoropoulos GE, Lazaris AC, Tzonou A., Keramopoulos A.Prognostic significance of the co-expression of p53 and c-erbB-2 proteins in breast cancer . J Pathol.1996;179:31-38.
44.
Gasparini G. , Weidner N., Bevilacqua P., et al. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol.1994;12:454-466.
45.
Sjogren S., Inganas M., Lindgren A., Holmberg L., Bergh J.Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers. J Clin Oncol.1998;16:462-469.
46.
Bianchi S., Paglierani M., Zampi G., et al. Prognostic significance of c-erbB-2 expression in node negative breast cancer. Br J Cancer.1993;67:625-629.
47.
Paik S., Hazan R., Fisher ER, et al. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol.1990 ;8:103-112.
48.
Makar AP, Desmedt EJ, De Potter CR, Vanderheyden JS, Schatteman EANeu (C-erbB-2) oncogene in breast cancer and its possible association with the risk of distant metastases. A retrospective study and review of literature . Acta Oncol.1990;29:931-934.
49.
Baker SJ, Fearon ER, Nigro JM, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989;244:217-221.
Avila MA, Velasco JA, Cansado J., Notario V.Quercetin mediates the down-regulation of mutant p53 in the human breast cancer cell line MDA-MB468. Cancer Res.1994;54:2424-2428.
52.
Finlay CA, Hinds PW, Levine AJThe p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989;57:1083-1093.
Walker RA, Dearing SJ, Lane DP, Varley JMExpression of p53 protein in infiltrating and in-situ breast carcinomas. J Pathol.1991;165:203-211.
55.
Crawford LV , Pim DC, Bulbrook RDDetection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer.1982;30: 403-408.
56.
McGuire WLBreast cancer prognostic factors: evaluation guidelines. J Natl Cancer Inst.1991;83:154-155.
57.
Davidoff AM , Herndon JE 2nd, Glover NS, et al. Relation between p53 overexpression and established prognostic factors in breast cancer. Surgery.1991;110: 259-264.
58.
Elledge RM, Fuqua SA, Clark GM, Pujol P., Allred DC, William L.McGuire Memorial Symposium. The role and prognostic significance of p53 gene alterations in breast cancer. Breast Cancer Res Treat. 1993;27:95-102.
59.
Davidoff AM , Kerns BJ, Iglehart JD, Marks JRMaintenance of p53 alterations throughout breast cancer progression. Cancer Res.1991 ;51:2605-2610.
60.
Nowell PCThe clonal evolution of tumor cell populations. Science.1976;194:23-28.
61.
Ostrowski JL , Sawan A., Henry L., et al. p53 expression in human breast cancer related to survival and prognostic factors: an immunohistochemical study. J Pathol.1991; 164:75-81.
62.
Pratap R., Shousha S.Breast carcinoma in women under the age of 50: Relationship between p53 immunostaining, tumour grade, and axillary lymph node status. Breast Cancer Res Treat.1998;49:35-39.
63.
Caleffi M., Teague MW, Jensen RA, Vnencak-Jones CL, Dupont WD, Parl FFp53 gene mutations and steroid receptor status in breast cancer. Clinicopathologic correlations and prognostic assessment. Cancer. 1994;73: 2147-2156.
64.
Porter PL, Gown AM, Kramp SG, Coltrera MDWidespread p53 overexpression in human malignant tumors. An immunohistochemical study using methacarnfixed, embedded tissue. Am J Pathol.1992;140:145-153.
65.
Chang K., Ding I., Kern FG, Willingham MCImmunohistochemical analysis of p53 and HER-2/neu proteins in human tumors . J Histochem Cytochem. 1991; 39: 1281-1287.
66.
Visscher DW, Sarkar FH, Wykes S., Kothari K., Macoska J., Crissman J.Clinicopathologic significance of p53 immunostaining in adenocarcinoma of the breast. Arch Pathol Lab Med.1993;117:973-976.
67.
Silvestrini R., Rao S., Benini E., Daidone MG, Pilotti S.Immunohistochemical detection of p53 in clinical breast cancers: a look at methodologic approaches. J Natl Cancer Inst.1995;87:1020.
68.
Elledge RM, Clark GM, Fuqua SA, Yu YY, Allred DCp53 protein accumulation detected by five different antibodies: relationship to prognosis and heat shock protein 70 in breast cancer. Cancer Res.1994;54:3752-3757.
69.
Beck T., Weller EE, Weikel W., Brumm C., Wilkens C., Knapstein PGUsefulness of immunohistochemical staining for p53 in the prognosis of breast carcinomas: correlations with established prognosis parameters and with the proliferation marker, MIB-1. Gynecol Oncol.1995;57:96-104.
70.
Borg A., Lennerstrand J., Stenmark-Askmalm M., et al. Prognostic significance of p53 overexpression in primary breast cancer; a novel luminometric immunoassay applicable on steroid receptor cytosols . Br J Cancer.1995;71: 1013-1017.
71.
MacGrogan G. , Bonichon F., de Mascarel I., et al. Prognostic value of p53 in breast invasive ductal carcinoma: an immunohistochemical study on 942 cases. Breast Cancer Res Treat.1995;36:71-81.
72.
Gasparini G. , Toi M., Verderio P., et al. Prognostic significance of p53, angiogenesis, and other conventional features in operable breast cancer: subanalysis in node-positive and node-negative patients. Int J Oncol.1998;12:1117-1125.
73.
Reed W., Hannisdal E., Boehler PJ, Gundersen S., Host H., Marthin J.The prognostic value of p53 and c-erb B-2 immunostaining is overrated for patients with lymph node negative breast carcinoma: a multivariate analysis of prognostic factors in 613 patients with a follow-up of 14-30 years. Cancer.2000;88:804-813.
74.
Sirvent JJ, Salvado MT, Santafe M., et al. p53 in breast cancer. Its relation to histological grade, lymph-node status, hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2. Immunohistochemical study of 153 cases. Histol Histopathol . 1995;10:531-539.
75.
Rosen PP, Lesser ML, Arroyo CD, Cranor M., Borgen P., Norton L.p53 in node-negative breast carcinoma: an immunohistochemical study of epidemiologic risk factors, histologic features, and prognosis. J Clin Oncol.1995;13:821-830.
76.
Clahsen PC, van de Velde CJ, Duval C., et al. p53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer. J Clin Oncol.1998; 16:470-479.
