erbB-2 Oncoprotein Expression in Breast Carcinoma:Poor Prognosis Associated With High Degree of Cytoplasmic Positivity Using CB-11 Antibody

Abstract

e r b B -2 O n c o p r o t e i n E x p r e s s i o n i n B r e a s t C a r c i n o m aThe relationship between immunohistochemically measured membranous expression of erbB-2 oncoprotein and prognosis in breast cancer is controversial, and the relationship between cytoplasmic positivity and prognosis has been minimally investigated.The clinical course of 300 women with infiltrating breast carcinoma, whose tumors were stained for erbB-2 oncoprotein with CB-11 monoclonal antibody, was followed for 5 to 79 months (median, 41 months). Higher numbers of cancer-related deaths were observed in patients with moderate-to-strong cytoplasmic positivity (15/60, 25%) and strong membranous positivity (9/29, 31%) than in patients with negatively stained tumors (8/53, 15%) or tumors with weaker degrees of cytoplasmic or membranous positivity (rate similar to or less than negative tumors). Relapsefree survival was also significantly shorter in patients with Because of the variable clinical course of breast cancer, identification of prognostic factors is of great interest.1,2 One of the proposed prognostic factors is the erbB-2 (HER-2/neu) oncogene, 3 which encodes a 185-kd glycoprotein on the cell surface that has tyrosine kinase activity and shows structural similarities to the epidermal growth factor receptor. 3,4 There is amplification of the erbB-2 oncogene or overexpression of the protein product in approxim a t e l y 15% to 30% of b r e a s t c a r c i n o m a s .

Defining a Test for HER-2/neu Evaluation in Breast Cancer in the Diagnostic Setting

“…The significance of cytoplasmic staining seen with CB11 is controversial although most studies agree that it is a nonspecific finding. However, a few studies have demonstrated concordance between strong cytoplasmic staining and poor prognosis in a subset of node positive breast cancer patients (16). Thus for the present time only the membrane pattern of staining should be evaluated.…”

Testing for HER2 in Breast Cancer: A Continuing Evolution

“…Though cytoplasmic staining can be recognized in cases of breast cancer, it has not been shown to correlate with gene amplification [118], HER2 mRNA levels [134, 135], or have an association with poor prognosis in a subset of node-positive women [34]. One study, however, has shown an association between moderate to strong cytoplasmic staining of HER2 with poor prognosis [136]. Another limitation of IHC scoring system is interobserver variability, particularly in cases with moderate (2+) membrane staining [137, 138].…”

Oncoproteins and proliferation markers in synovial sarcomas: a clinicopathologic study of 19 cases

“…In most studies using immunohistochemical methods, only membranous staining is considered specific for Her2/neu and cytoplasmic staining is usually dismissed as non-specific. There are reports, however, on the clinical relevance of moderate to strong cytoplasmic expression of Her2/neu and its association with poor prognosis in patients with breast carcinoma, colorectal adenocarcinoma, and transitional cell carcinoma of the urinary bladder [22,23,24]. It has been hypothesized that the antibody binds to precursor forms of the Her2/neu protein located in the cytoplasm [22,23].…”

“…There are reports, however, on the clinical relevance of moderate to strong cytoplasmic expression of Her2/neu and its association with poor prognosis in patients with breast carcinoma, colorectal adenocarcinoma, and transitional cell carcinoma of the urinary bladder [22,23,24]. It has been hypothesized that the antibody binds to precursor forms of the Her2/neu protein located in the cytoplasm [22,23]. Another possibility is that the cytoplasmic staining reflects the process of internalization of the activated receptors, followed by their lysosomal uptake and degradation [25].…”