Serological and immunohistochemical HER-2/neu statuses do not correlate and lack prognostic value for ovarian cancer patients
M. HOOPMANN md
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorK. SACHSE md
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorM.M. VALTER md
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorM. BECKER technical assistant
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorM. ORTMANN md, phd
Institute of Pathology, University Hospital of Cologne, Cologne
Search for more papers by this authorU.-J. GÖHRING md, phd
Department of Obstetrics and Gynaecology, Johanniter-Krankenhaus Bonn, Johanniterstraße 3-5, Bonn
Search for more papers by this authorA. THOMAS md
Department of Obstetrics and Gynaecology, Charité Campus Mitte University Berlin, Charitéplatz 1, Berlin
Search for more papers by this authorP. MALLMANN md, phd
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorCorresponding Author
T. SCHÖNDORF phd
Institute for Clinical Research and Development, Parcusstraße 8, 55116 Mainz, Germany
Thomas Schöndorf, Institute for Clinical Research and Development, Parcusstraße 8, 55116 Mainz, Germany (e-mail: [email protected]).Search for more papers by this authorM. HOOPMANN md
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorK. SACHSE md
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorM.M. VALTER md
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorM. BECKER technical assistant
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorM. ORTMANN md, phd
Institute of Pathology, University Hospital of Cologne, Cologne
Search for more papers by this authorU.-J. GÖHRING md, phd
Department of Obstetrics and Gynaecology, Johanniter-Krankenhaus Bonn, Johanniterstraße 3-5, Bonn
Search for more papers by this authorA. THOMAS md
Department of Obstetrics and Gynaecology, Charité Campus Mitte University Berlin, Charitéplatz 1, Berlin
Search for more papers by this authorP. MALLMANN md, phd
Department of Obstetrics and Gynaecology, University Hospital of Cologne, Cologne, Germany
Search for more papers by this authorCorresponding Author
T. SCHÖNDORF phd
Institute for Clinical Research and Development, Parcusstraße 8, 55116 Mainz, Germany
Thomas Schöndorf, Institute for Clinical Research and Development, Parcusstraße 8, 55116 Mainz, Germany (e-mail: [email protected]).Search for more papers by this authorAbstract
HOOPMANN M., SACHSE K., VALTER M.M., BECKER M., NEUMANN R., ORTMANN M., GÖHRING U.-J., THOMAS A., MALLMANN P. & SCHÖNDORF T. (2010) European Journal of Cancer CareSerological and immunohistochemical HER-2/neu statuses do not correlate and lack prognostic value for ovarian cancer patients
The serodiagnostics of extracellular domain (ECD) HER-2/neu has turned into an evidenced-based tumour marker for HER-2/neu-positive breast cancer patients. This study investigated the clinical relevance of immunohistochemical and serum HER-2/neu in 44 patients with advanced ovarian cancer.
The Hercept-Test® from DAKO Diagnostics was used to analyse immunohistochemical HER-2/neu expression. The HER-2/neu ECD in serum was determined quantitatively by Bayer Immuno 1™ Immunoanalyser. The HER-2/neu serum values were correlated to the clinical course of disease and to established prognostic factors, i.e. progression-free and overall survival.
Some 23% of patients (n= 11) expressed HER-2/neu serum levels higher than 15 ng/mL, whereas only 7.7% (n= 2) of the patients examined by immunohistochemistry showed a HER-2/neu overexpression of the tissue. None of them revealed an overexpression of HER-2/neu ECD by serodiagnostics. HER-2/neu overexpression did not correlate significantly to any of the analysed prognostic factors. According to progression-free and overall survival, there was no significant difference between serologically HER-2/neu-positive or negative patients.
For ovarian cancer patients, neither high HER-2/neu serum levels, nor immunohistochemically determined HER-2/neu positivity, appear to predict the course of disease. This study shows a lack of association between the immunohistochemical HER-2/neu status and the serum level of solute extracelluar HER-2/neu domain.
REFERENCES
- Abendstein B., Daxenbichler G., Windbichler G., Zeimet A., Geurts A., Sweep F. & Marth C. (2000) Predictive value of uPA, PAI-1, HER-2 and VEGF in the serum of ovarian cancer patients. Anticancer Research 20, 569–572.
- Bargmann C.I., Hung M.C. & Weinberg R.A. (1986) Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p 185. Cell 45, 649–657.
- Baselga J. (2001) Is Circulating HER-2 more than just a tumour marker? Clinical Cancer Research 7, 2605–2607.
- Bast R.C., Xu F.J., Yu Y.H., Barnhill S., Zhang Z. & Mills G.B. (1998) CA 125: the past and the future. International Journal of Biology Markers 13, 179–187.
- Bookman M.A., Darcy K.M., Clarke-Pearson D., Boothby R.A. & Horowitz I.R. (2003) Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. Journal of Clinical Oncology 21, 283–290.
- Bristow R.E., Tomacruz R.S., Armstrong D.K., Trimble E.L. & Montz F.J. (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. Journal of Clinical Oncology 20, 1248–1259.
- Carney W.P., Neumann R., Lipton A., Leitzel K., Ali S. & Price C.P. (2003) Potential clinical utility of serum HER-2/neu in patients with breast cancer. Clinical Chemistry 49, 1579–1598.
- Cheung T.H., Wong Y.F., Chung T.K., Maimonis P. & Chang A.M. (1999) Clinical use of serum c-erbB-2 in patients with ovarian masses. Gynecologic Obstetrics & Investigation 48, 133–137.
- Cook G.B., Neaman I.E. Goldblatt J.L., Cambetas D.R., Hussain M., Lüftner D., Yeung K.K., Chan D.W., Schwartz M.K. & Allard W.J. (2001) Clinical Utility of Serum HER-2/neu Testing on the Bayer Immuno 1® Automated System in Breast Cancer. Anticancer Research 21, 1465–1470.
- Crawford S.M. & Peace J. (2005) Does the nadir CA125 concentration predict a long-term outcome after chemotherapy for carcinoma of the ovary? Annals in Oncology 16, 47–50.
- Fehm T., Jäger W., Kraemer S., Sohn C., Solomayer-Meyberg G., Solomayer E.F., Kurek R., Wallwiener D. & Gebauer G. (2004) Changes of serum HER2 during clinical course of metastatic breast cancer patients. Anticancer Research 24, 4205–4210.
- Fornier M., Seidman A., Schwartz M., Ghani F., Thiel R., Norton L. & Hudis C. (2005) Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunhistochemistry and fluorescence in situhybridization and with response rate. Annals of Oncology 16, 234–239.
- Goldhirsch A., Glick J.H., Gelber R.D., Coates A.S., Thurlimann B. & Senn H.J. (2005) Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Annals of Oncology 16, 1569–1583.
- Hellström I., Goodman G., Pullman J., Yang Y. & Hellström K. (2001) Overexpression of HER-2 in ovarian carcinomas. Cancer Research 61, 2420–2423.
- Hogdall E.V., Christensen L., Kjaer S.K., Blaakaer J., Bock J.E., Glud E., Norgarrd-Pedersen B. & Hogdall C.K. (2003) Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma: from the Danish MALOVA Ovarian Cancer Study. Cancer 98, 66–73.
- Iwamoto H., Fukasawa H., Honda T., Hirata S. & Hoshi K. (2003) HER-2/neu expression in ovarian clear cell carcinomas. International Journal of Gynecologic Cancer 13, 28–31.
- Lassus H., Leminen A., Vayrynen A., Cheng G., Gustafasson J.A., Isola J. & Butzow R. (2004) ERBB2 amplification is superior to protein expression status in predicting patient outcome in serous ovarian carcinoma. Gynecologic Oncology 92, 31–39.
- Leong A.S. (2004) Pitfalls in diagnostic immunhistology. Advances in Anatomy Pathology 11, 86–93.
- Meden H. & Kuhn W. (1997) Overexpression of the oncogene c-erbB-2 (HER-2/neu) in ovarian cancer: a new prognostic factor. European Journal of Obstetrics Gynecology & Reproductive Biology 71, 173–179.
- Meden H., Marx D., Roegglen T., Schauer A. & Kuhn W. (1998) Overexpression of the oncogene c-erbB-2 (HER2/neu) and response to chemotherapy in patients with ovarian cancer. International Journal of Gynecologic Pathology 17, 61–65.
- Meden H., Marx D., Schauer A., Wuttke W. & Kuhn W. (1997) Prognostic significance of p105 (c-erbB-2, HER-2/neu) serum levels in patients with ovarian cancer. Anticancer Research 17, 757–760.
- Payne R., Allard J., Anderson-Mauser L., Humphreys J., Tenney D. & Morris D. (2000) Automated Assay for HER-2/neu in Serum. Clinical Chemistry 46, 175–182.
- Piccart-Gebhart M.J., Procter M., Leyland-Jones B., Goldhirsch A., Untch M., Smith I., Gianni L., Baselga J., Bell R., Jackisch C., Cameron D., Dowsett M., Barrios C.H., Steger G., Huang C.S., Andersson M., Inbar M., Lichinitser M., Láng I., Nitz U., Iwata H., Thomssen C., Lohrisch C., Suter T.M., Rüschoff J., Suto T., Greatorex V., Ward C., Straehle C., McFadden E., Dolci M.S. Gelber R.D., & Herceptin Adjuvant (HERA) Trial Study Team. (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353, 1659–1672.
- Reibenwein J. & Krainer M. (2008) Targeting signaling pathways in ovarian cancer. Expert Opinion Therapy Targets 12, 353–365.
- Riener E.K., Arnold N., Kommoss F., Lauinger S. & Pfisterer J. (2004) The prognostic and predictive value of immunohistochemically detected HER-2/neu overexpression in 361 patients with ovarian cancer: a multicenter study. Gynecological Oncology 95, 89–94.
-
Rubin S.C.,
Finstad C.L.,
Federici M.G.,
Scheiner L.,
Lloyd K.O. &
Hoskins W.J. (1994) Prevalence and significance of HER-2/neu expression in early epithelial ovarian cancer.
Cancer
73, 1456–1459.
10.1002/1097-0142(19940301)73:5<1456::AID-CNCR2820730522>3.0.CO;2-L PubMed Web of Science® Google Scholar
- Schippinger W., Regitnig P., Bauernhofer T., Ploner F., Hofmann G., Krippl P., Wehrschütz M., Lax S., Carney W., Neumann R., Wernecke K.D. & Samonigg H. (2004) The course of serum HER-2/neu levels as an independent prognostic factor for survival in metastatic breast cancer. Oncology Reports 11, 1331–1336.
- Schöndorf T., Hoopmann M., Warm M., Neumann R., Thomas A., Göhring U.-J., Eisberg C. & Mallmann P. (2002) Serologic concentrations of HER-2/neu in breast cancer patients with visceral metastases receiving trastuzumab therapy predict the clinical course. Clinical Chemistry 48, 1360–1362.
- Serrano-Olvera A., Dueñas-Gonzales A., Gallardo-Rincón D., Candelaria M. & De la Garza-Salazar J. (2006) Prognostic, predictive and therapeutic implications of HER2 in invasive epithelial ovarian cancer. Cancer Treatment Reviews 32, 180–190.
- Shih C., Padhy L., Murray M. & Weinberg R.A. (1981) Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature 260, 261–264.
- Slamon D.J., Clark G., Wong S.G., Levin W.J., Ullrich A. & McGuire W. (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177–182.
- Slamon D.J., Godolphin W., Jones L.A., Holt J.A., Wong S.G., Keith D.E., Levin W.J., Stuart S.G., Udove J., Ullrich A. & Press M.F. (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244, 707–712.
- Steffensen K.D., Waldstrom M., Jeppensen E., Jakobsen E., Brandslund I. & Jakobsen A. (2007) The prognostic importance of cyclooxigenase 2 and HER2 expression in epithelial ovarian cancer. International Journal of Gynecological Cancer 17, 798–807.
- Tse C., Brault D., Gligorov J., Antoine M., Neumann R., Lotz J. & Capeau J. (2005) Evaluation of the quantitative analytical methods real-time PCR for HER-2 gene quantification and ELISA of serum HER-2 protein and comparison with fluorescence in situ hybridization and immunhistochemistry for determining HER-2 status in breast cancer patients. Clinical Chemistry 51, 1093–1101.
- Verri E., Gugliemini P., Puntoni M., Perdelli L., Papadia A., Lorenzi P., Rubagotti A., Ragni N. & Boccardo F. (2005) HER2/neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence significance. Clinical Study Oncology 68, 154–161.
