Elsevier

Human Pathology

Volume 23, Issue 9, September 1992, Pages 974-979
Human Pathology

Original contribution
Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer

https://doi.org/10.1016/0046-8177(92)90257-4Get rights and content

Abstract

Using permanent-section immunohistochemistry, we investigated the role of HER-2/neu in the development and progression of human breast cancer by measuring its overexpression in a series of hyperplastic (n = 30), dysplastic (n = 15), and malignant neoplastic (n = 708) lesions of ductal epithelium and by evaluating the relationships between overexpression and clinicopathologic features known to have prognostic significance in these lesions. The neoplasms included pure ductal carcinoma in situ (DCIS; n = 59) and infiltrating ductal carcinoma (IDC; n = 649). The latter were all node negative and stratified into IDC combined (n = 237) or not combined (n = 412) with a “significant amount” of DCIS (defined as DCIS ≥ 10% of total tumor cellularity). Overexpression of HER-2/neu was not observed in any of the hyperplastic or dysplastic lesions. In contrast, it was present in 56% of pure DCIS and in 77% of the comedo subtype of this group. Only 15% of IDC overexpressed HER-2/neu. However, the rate of overexpression was significantly higher in the subset of IDC combined with DCIS compared with the subset of IDC not combined with DCIS (22% ν 11%, respectively; P < .0001). These results are consistent with the hypothesis that HER-2/neu plays a more important role in initiation than in progression of ductal carcinomas. They also suggest that overexpression decreases within individual tumors as they evolve from in situ to increasingly invasive lesions or, alternatively, that many invasive carcinomas arise de novo (ie, without progressing through a significant in situ stage) by mechanisms not involving HER-2/neu. In addition, overexpression of HER-2/neu was associated with several poor prognostic features (younger patient age, premenopause, negative estrogen receptor status, negative progesterone receptor status, and high nuclear grade) in the subset of IDC combined with DCIS. With one exception (negative estrogen receptor status) these associations were lost in IDC not combined with DCIS, also suggesting that the role of HER-2/neu changes during the progression of human breast cancer.

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  • Cited by (0)

    This intergroup study (INT 0076, EST 7186, SWOG 8696) was coordinated by the Eastern Cooperative Oncology Group (Chairman, Paul P. Carbone, MD; NCI grants no. CA21115, CA23318, and CA30195). The results were presented at the 1990 annual meeting of the American Society of Clinical Oncology. The late William L. McGuire was a Clinical Research Professor of the American Cancer Society.

    Deceased.

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