A novel method of reporting c-erbB-2 overexpression: Correlation with grade but not with other prognostic parameters in breast cancer

A novel method of reporting c-erbB-2 overexpression: Correlation with grade but not with other prognostic parameters in breast cancer

Overexpression of erbB-2 protein is a marker of clinically aggressive behavior in breast cancer patients. In general erbB- 2 status is reported on a scale from negative to 3+, depending on staining intensity, if more than 10% of the tumor cells are stained. However, the original definition does not take into account the percentage of stained cells in detail, since all samples score in the same way if they are above the cut-off, established at 10%. In this study, we evaluated the erB-B2 overexpression by immunohistochemistry in 169 patients and evaluated any correlation with the other well known prognostic parameters. We also tested whether there was a difference between the original definition of c-erbB-2 positivity (2+ or 3+) and a novel system, the total c-erbB-2 score, which takes into account both the percentage, and intensity of staining as a continuous variable. The total c-erbB-2 score was correlated with the grade (P = 0.006) but not with other parameters. When 2+ and 3+ levels of staining together were regarded as positive, a similar correlation with grade was demonstrated. However, when only 3+ cases were considered, there was no significant correlation. In conclusion reporting c-erbB-2 as a continuous variable may make more sense than treating a cut-off value as positive.

___

  • 1. Neve RM, Lane HA, Hynes NE. The role of overexpressed Her2 in transformation. Annals Oncol 12 (suppl. 1): 9-13, 2001. 2. Bozcuk H, Uslu G, Pestereli E, et al. Predictors of distant metastasis at presentation in breast cancer: A study also evaluating associations among common biologic indicators. Breast Cancer Res Tr 68: 239-248, 2001. 3. Thor AD, Berry DA, Budman DR, et al. erbB-2, p53, and the efficacy of adjuvant therapy in lymph node positive breast cancer. J Natl Cancer Inst 90: 1346-1360, 1998. 4. Paik S, Bryant J, Park C et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive hormone receptornegative breast cancer. J Natl Cancer Inst 90: 1361-1370, 1998. 5. Yamauchi H, OÕNeill A, Gelman R, et al. Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels or extracellular domain of the Her- 2/c-neu protein. J Clin Oncol 15: 2518-2525, 1997. 6. Elledge RM, Green S, Ciocca D, et al. HER-2 expression and response to tamoxifen in estrogen receptor-positive breast cancer: a Southwest Oncology Group Study. Clin Cancer Res 4: 7- 12, 1998. 7. Berger MS, Locher GW, Saurer S, et al. Correlation of c-erbB-2 gene amplification and protein expression of human breast carcinoma with nodal status and nuclear grading. Cancer Res 48: 1238-1243, 1988. 8. Elston CW, Ellis IO. Pathological 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 19: 403-10, 1991. 9. Press MF, Pike MC, Chazin VR, et al. Her-2/neu expression in node-negative breast cancer: Direct tissue quantitation by computerized image analysis and association with overexpression with increased risk of recurrent disease. Cancer Res 53: 4960- 4970, 1993. 10. Press MF, Bernstein L, Thomas PA, et al. HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. J Clin Oncol 15: 2894-2904, 1997. 11. Idris N, Carothers Carraway CA, Carraway KL. Differential localization of ErbB2 in different tissues of the rat female reproductive tract: implications for the use of specific antibodies for ErbB2 analysis. J Cell Physiol 189: 162-70, 2001. 12. Menard S, Valagussa P, Pilotti S, et al. Response to cyclophosphamide, methotrexate, and fluorouracil in lymph nodepositive breast cancer according to HER2 overexpression and other tumor biologic variables. J Clin Oncol 19: 329-35, 2001. 13. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer TrialistsÕ Collaborative Group. Lancet 351(9114): 1451-67, 1998. 14. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER- 2/neu oncogene. Science 235: 177-82, 1987. 15. Tsuda H, Hirohashi S, Shimosato Y, et al. Correlation between histologic grade of malignancy and copy number of c-erbB-2 gene in breast carcinoma. A retrospective analysis of 176 cases. Cancer 65: 1794-80, 1990. 16. Hoff ER, Tubbs RR, Myles JL, et al. HER2/neu amplification in breast cancer: stratification by tumor type and grade. Am J Clin Pathol 117: 916-21, 2002. 17. 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 8: 103-12, 1990. 18. Konecny G, Pauletti G, Pegram M, et al. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 15: 142-53, 2003. 19. Ariazi EA, Clark GM, Mertz JE. Estrogen-related receptor alpha and estrogen-related receptor gamma associate with unfavorable and favorable biomarkers, respectively, in human breast cancer. Cancer Res 62: 6510-8, 2002. 20. Roux-Dosseto M, Romain S, Dussault N, et al. Correlation of erbB-2 gene amplification with low levels of estrogen and/or progesterone receptors in primary breast cancer: do erbB-2 products delineate hormone-independent tumors? Biomed Pharmacother 43: 641-9, 1989. 21. Bouras T, Southey MC, Venter DJ. Overexpression of the steroid receptor coactivator AIB1 in breast cancer correlates with the absence of estrogen and progesterone receptors and positivity for p53 and HER2/neu. Cancer Res 61: 903-7, 2001. 22. Keshgegian AA. ErbB-2 oncoprotein overexpression in breast carcinoma: inverse correlation with biochemically- and immunohistochemically-determined hormone receptors. Breast Cancer Res Treat 35: 201-10, 1995. 23. Querzoli P, Marchetti E, Fabris G, et al. Immunohistochemical expression of c-erbB-2 in human breast cancer by monoclonal antibody: correlation with lymph node and ER status. Tumori 76: 461-4, 1990. 24. Bohn U, Aguiar J, Bilbao C et al. Prognostic value of the quantitative measurement of the oncoprotein p185(Her-2/neu) in a group of patients with breast cancer and positive node involvement. Int J Cancer 101: 539-44, 2002. 25. Sutterlin MW, Haller A, Gassel AM, et al. The correlation of cerbB- 2 oncoprotein and established prognostic factors in human breast cancer. Anticancer Res 20: 5083-8, 2000.