Annals of Oncology Advance Access originally published online on March 19, 2007
Annals of Oncology 2007 18(6):1004-1014; doi:10.1093/annonc/mdm074
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© 2007 European Society for Medical Oncology
breast cancer |
Prognostic relevance of a novel semiquantitative classification of Bcl2 immunohistochemical expression in human infiltrating ductal carcinomas of the breast
1 Department of Experimental Pathology, Unit of Clinical Pathology
2 Department of Surgical Pathology
3 Department of Statistics
4 Department of Surgery, University of Bologna, Italy
* Correspondence to: Dr D. Treré, Alma Mater Studiorum, Università di Bologna, Dipartimento di Patologia Sperimentale, Via San Giacomo 14, 40126 Bologna, Italy. Tel: +39-051-302874; Fax: +39-051-306861; E-mail: davide.trere{at}unibo.it
Background: Bcl2 is an important prognostic parameter in human breast cancer. However, the evaluation of Bcl2 expression by immunohistochemistry is carried out using arbitrary scoring criteria. In the present study, we evaluated the clinical relevance of a novel, semiquantitative classification of the Bcl2 immunostaining based on both the distribution and the intensity of the staining reaction.
Patients and methods: The proposed classification was first validated in 69 breast cancer specimens by comparing the Bcl2 immunostaining with the Bcl2 messenger RNA (mRNA) levels evaluated by real-time RT-PCR. Since a highly significant association was found between protein and mRNA for Bcl2, the immunohistochemical scoring system was applied to 442 patients with infiltrating ductal carcinomas of the breast with long-term follow-up (median observation time 106 months).
Results: In the entire series, the Bcl2 variable was an independent predictor of clinical outcome, and its prognostic independence was maintained when lymph node-negative and -positive patients were considered separately. In this regard, of particular interest was the observation of a subgroup of node-negative breast cancer patients with a negative Bcl2 immunostaining, who had a very high probability of relapse or death (respectively about five and seven times greater than patients with a positive Bcl2 immunostaining). Moreover, the Bcl2 variable retained prognostic significance also in subgroups of patients treated with either adjuvant endocrine therapy or chemotherapy.
Conclusions: Our results demonstrated that in breast cancer, Bcl2 protein expression parallels its mRNA level, and it has a highly significant and independent prognostic relevance.
Key words: adjuvant therapy, breast cancer, Bcl2 expression, immunohistochemistry, prognosis, real-time RT-PCR
Received for publication November 15, 2006. Revision received January 31, 2007. Accepted for publication February 1, 2007.