Original Paper
The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-I in node-negative breast cancer
Vibeke Jensen,
Morten Ladekarl,
Peter Holm-Nielsen,
Flemming Melsen,
Flemming Brandt Sœrensen,
Corresponding Author
Vibeke Jensen
Institute of Pathology, Aarhus Amtssygehus, Denmark
Institute of Pathology, Aarhus University Hospital, Amtssygehuset, Tage Hansens Gade 2, 8000 Aarhus C, DenmarkSearch for more papers by this authorMorten Ladekarl
Sterological Research Laboratory, University of Aarhus, Denmark
Search for more papers by this authorPeter Holm-Nielsen
Institute of Pathology, Aarhus Amtssygehus, Denmark
Search for more papers by this authorFlemming Melsen
Institute of Pathology, Aarhus Amtssygehus, Denmark
Search for more papers by this authorFlemming Brandt Sœrensen
University Institute of Pathology, Aarhus Kommunehospital, Denmark
Search for more papers by this authorVibeke Jensen,
Morten Ladekarl,
Peter Holm-Nielsen,
Flemming Melsen,
Flemming Brandt Sœrensen,
Corresponding Author
Vibeke Jensen
Institute of Pathology, Aarhus Amtssygehus, Denmark
Institute of Pathology, Aarhus University Hospital, Amtssygehuset, Tage Hansens Gade 2, 8000 Aarhus C, DenmarkSearch for more papers by this authorMorten Ladekarl
Sterological Research Laboratory, University of Aarhus, Denmark
Search for more papers by this authorPeter Holm-Nielsen
Institute of Pathology, Aarhus Amtssygehus, Denmark
Search for more papers by this authorFlemming Melsen
Institute of Pathology, Aarhus Amtssygehus, Denmark
Search for more papers by this authorFlemming Brandt Sœrensen
University Institute of Pathology, Aarhus Kommunehospital, Denmark
Search for more papers by this authorAbstract
The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low-risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter ⩽50 mm, and no histological evidence of invasion of skin or deep fascia (=T1N0M0 and T2N0M0). The median follow-up time was 104 months (range 5–143 months). Immunohistochemical analysis of OA-519 expression was performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity was estimated using a Ki-67 equivalent monoclonal antibody (MIB-1), which is applicable on formalin-fixed, paraffin-embedded tissue after microwave pretreatment. OA-519 was expressed in about one-third of the tumours and the percentage of proliferating cells (the MIB-1 index) ranged between 1 and 72 per cent (median 17 per cent). Using multivariate Cox analysis, both the MIB-1 index and OA-519 expression were of independent prognostic value (2p⩽0·01), and the combined immunohistological approach may therefore be useful in selecting patients with node-negative breast cancer who might benefit from adjuvant therapy.
References
- 1 Rosen PB, Groshen S, Kinne DW, Norton L Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up. J Clin Oncol 1993; 11: 2090–2100.
- 2
Valagussa P,
Bonadonna G,
Veronesi U
Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients.
Cancer
1978;
41:
1170–1178.
10.1002/1097-0142(197803)41:3<1170::AID-CNCR2820410355>3.0.CO;2-I CASPubMedWeb of Science®Google Scholar
- 3 Kuhajda FP, Piantadosi S, Pasternack GR Haptoglobin-related protein (Hpr) epitopes in breast cancer as a predictor of recurrent of the disease. N Engl J Med 1989; 321: 636–641.
- 4 Shurbaji MS, Pastenack GR, Kuhajda FP Expression of haptoglobin-related protein in primary and metastatic breast cancers. A longitudinal study of 48 fatal tumours. Am J Clin Pathol 1991; 96: 238–242.
- 5 Kuhajda FP, Katumuluwa AI, Pasternack GR Expression of haptoglobin-related protein and its potential role as a tumor antigen. Proc Natl Acad Sci USA 1989; 86: 1188–1192.
- 6 Kuhjda FP, Jenner K, Wood FD et al. Fatty acid synthesis: a potential selective target for antineoplastic therapy. Submitted.
- 7 Shurbaji MS, Kuhajda FP, Pasternack GR, Thurmond TS Expression of oncogenic antigen 519 (OA-519) in prostate cancer is a potential prognostic indicator. Am J Clin Pathol 1992; 97: 686–691.
- 8
Clayton F
Pathologic correlates of survival in 378 lymph nodenegative infiltrating ductal breast carcinomas. Mitotic count is the best single predictor.
Cancer
1991;
68:
1309–1327.
10.1002/1097-0142(19910915)68:6<1309::AID-CNCR2820680621>3.0.CO;2-I CASPubMedWeb of Science®Google Scholar
- 9
Gentili C,
Sanfilippo O,
Silvestrini R
Cell proliferation and its relationship to clinical features and relapse in breast cancers.
Cancer
1981;
48:
974–979.
10.1002/1097-0142(19810815)48:4<974::AID-CNCR2820480420>3.0.CO;2-# CASPubMedWeb of Science®Google Scholar
- 10
Sasaki K,
Matsumura K,
Tsuji T,
Shinozaki F,
Takahashi M
Relationship between labelling indices of Ki-67 and BrdUrd in human malignant tumors.
Cancer
1988;
62:
989–993.
10.1002/1097-0142(19880901)62:5<989::AID-CNCR2820620525>3.0.CO;2-U CASPubMedWeb of Science®Google Scholar
- 11 Sahin AA, Ro JY, El-Nagger AK et al. Tumor proliferative fraction in solid malignant neoplasms. A comparative study of Ki-67 immunostaining and flow cytometric determinations. Am J Clin Pathol 1991; 96: 512–519.
- 12
Dressler LG,
Seamer LC,
Owens MA,
Clark GM,
McGuire WL
DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens.
Cancer
1988;
61:
420–427.
10.1002/1097-0142(19880201)61:3<420::AID-CNCR2820610303>3.0.CO;2-0 CASPubMedWeb of Science®Google Scholar
- 13 Gerdes J, Schwab U, Lemke H, Stein H Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983; 31: 13–20.
- 14 Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984; 133: 1710–1715.
- 15 Key G, Becker MHG, Baron B et al. New Ki-67 equivalent murine monoclonal antibodies (MIB-1–3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest 1993; 68: 629–636.
- 16 Cattoretti G, Becker MHG, Key G et al. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol 1992; 168: 357–363.
- 17 Shi SR, Key ME, Kalra KL Antigen retrieval in formalin-fixed, paraffin-embedded tissue: an enhancement method for immunohis-tochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 1991; 39: 741–748.
- 18 Spiessl B, Beahrs OH, Hermanek P et al. TNM Atlas. Illustrated Guide to the TNP/pTNM classification of Malignant Tumours. UICC International Union Against Cancer. 3rd edn. New York: Springer-Verlag, 1989: 173–183.
- 19 Bloom HJG, Richardson WW Histological grading and prognosis in breast cancer. A study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 1957; 11: 359–377.
- 20 Gundersen HJG Notes on the estimation of the numerical density of arbitrary profiles: the edge effect. J Microsc 1977; 111: 219–223.
- 21 Gerdes J, Dallenbach F, Lennert K Growth fractions in malignant non-Hodgkin's lymphomas (NHL) as determined in situ with the monoclonal antibody Ki-67. Hematol Oncol 1984; 2: 365–371.
- 22 Gerdes J, Lelle RJ, Pickartz H et al. Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67. J Clin Pathol 1986; 39: 977–980.
- 23
Veronese SM,
Gambacorta M,
Gottardi O,
Scanzi F,
Ferrario M,
Lampertico P
Proliferation index as a prognostic marker in breast cancer.
Cancer
1993;
71:
3926–3931.
10.1002/1097-0142(19930615)71:12<3926::AID-CNCR2820711221>3.0.CO;2-2 CASPubMedWeb of Science®Google Scholar
- 24
Wintzer HO,
Zipfel I,
Schulte-Monting J,
Hellerich U,
von Kleist S,
Ki-67 immunostaining in human breast tumors and its relationship to prognosis.
Cancer
1991;
67:
421–428.
10.1002/1097-0142(19910115)67:2<421::AID-CNCR2820670217>3.0.CO;2-Q CASPubMedWeb of Science®Google Scholar
- 25 Bouzubar N, Walker KJ, Griffith K et al. Ki-67 immunostaining in primary breast cancer: pathological and clinical associations. Br J Cancer 1989; 59: 943–947.
- 26
Sahin AA,
Ro J,
Ro JY et al.
Ki-67 immunostaining in nodenegative state I/II breast carcinoma. Significant correlation with prognosis.
Cancer
1991;
68:
549–557.
10.1002/1097-0142(19910801)68:3<549::AID-CNCR2820680318>3.0.CO;2-J CASPubMedWeb of Science®Google Scholar
- 27 Gerdes J, Stein H, Pileri S et al. Prognostic relevance of tumour cell growth fractions in malignant non-Hodgkin's lymphomas. Lancet 1987; 2: 448–449.
- 28 Kuhajda FP, Eggleston JC Pregnancy-associated plasma protein A. A clinically significant predictor of early recurrence in stage I breast carcinoma is independent of estrogen receptor status. Am J Pathol 1985; 121: 342–348.
- 29 Kuhajda FP, Abeloff MD, Eggleston JC Pregnancy-associated plasma protein A: a clinically significant predictor of early recureence in stage II breast carcinoma. Hum Pathol 1985; 16: 228–235.
- 30 Bacus SS, Goldschmidt R, Chin D, Moran G, Weinberg D, Bacus JW Biological grading of breast cancer using antibodies to prolif-erating cell and other markers. Am J Pathol 1989; 135: 783–792.
- 31 Aaltomaa S, Lipponen P, Eskelinen M et al. Hormone receptors as prognostic factors in female breast cancer. Ann Med 1991; 23: 643–648.
- 32 Charpin C, Andrac L, Vacheret H et al. Multiparametric evaluation (SAMBA) of growth fraction (monoclonal Ki67) in breast carcinoma tissue sections. Cancer Res 1988; 4368–4374.
- 33 Bilous AM, McKay M, Milliken J A comparison between Ki-67 antibody reactivity and other pathological variables in breast carcinoma. Pathology 1991; 23: 282–285.
- 34 Marchetti E, Querzoli P, Marzola A et al. Assessment of proliferative rate of breast cancer by Ki-67 monoclonal antibody. Mod Pathol 1990; 3: 31–35.
- 35 Barnard NJ, Hall PA, Lemoine NR, Kadar N Proliferative index determined in situ by Ki67 immunostaining and its relationship to clinical and pathological variables. J Pathol 1987; 152: 287–295.
- 36 Wrba F, Chott A, Reiner A et al. Ki-67 immunoreactivity in breast carcinomas in relation to transferrin receptor expression, estrogen receptor status and morphological criteria. Oncology 1989; 46: 255–259.
- 37 Helin ML, Helle MJ, Helin HJ, Isola JJ Proliferative activity and steroid receptors determined by immunohistochemistry in adjacent frozen sections of 102 breast carcinomas. Arch Pathol Lab Med 1989; 113: 854–857.
- 38 Weikel W, Beck T, Mitze M, Knapstein PG Immunohistochemical evaluation of growth fractions in human breast cancer using monoclonal antibody Ki-67. Breast Cancer Res Treat 1991; 18: 149–154.
- 39 Gerdes J, Pickartz H, Brotherton J, Hammerstein J, Weitzel H, Stein H Growth fractions and estrogen receptors in human breast cancers as determined in situ with monoclonal antibodies. Am J Pathol 1987; 129: 486–492.
- 40 Leonardi E, Girlando S, Serio G et al. PCNA and Ki-67 expression in breast carcinoma: correlations with clinical and biological variables. J Clin Pathol 1992; 45: 416–419.
- 41 Gasparini G, Dal Fior S, Pozza F, Bevilacqua P Correlation of growth fraction by Ki-67 immunohistochemistry with histological factors and hormone receptors in operable breast carcinoma. Breast Cancer Res Treat 1989; 14: 329–336.
- 42 Thorpe SM, Rose C, Rasmussen BB et al. Prognostic value of steroid hormone receptors: multivariate analysis of systematically untreated patients with node negative primary breast cancer. Cancer Res 1987; 15: 6126–6133.
