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NH2-terminal Truncated HER-2 Protein but not Full-Length Receptor Is Associated with Nodal Metastasis in Human Breast Cancer
Background: The full-length receptor p185HER-2 undergoes a metalloprotease-dependent cleavage producing a membrane-associated fragment (p95HER-2) in cultured breast cancer cells. P95HER-2 has potentially enhanced signaling activity, but its expression and role in human breast cancer is poorly charac...
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Published in: | Clinical cancer research 2002-02, Vol.8 (2), p.347-353 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | Background: The full-length receptor p185HER-2 undergoes a metalloprotease-dependent cleavage producing a membrane-associated fragment
(p95HER-2) in cultured breast cancer cells. P95HER-2 has potentially enhanced signaling activity, but its expression and role
in human breast cancer is poorly characterized.
Purpose: The purpose of this project was to characterize the expression of p95HER-2 in primary breast cancers and nodal metastasis,
and to study association with clinicopathological factors.
Experimental Design: P95HER-2 and p185HER-2 were examined in 337 primary breast tumors and 81 metastatic lymph nodes by Western blot analysis,
and tested for associations with other clinicopathological factors.
Results: P95HER-2 was present in 20.9% of primary tumors from node-negative patients, in 29.1% from patients with one to three metastatic
nodes, and in 36.7% from patients with four or more metastatic nodes ( P = 0.027). Whereas p185HER-2 overexpression was unrelated to nodal disease ( P = 0.63), the odds of lymph node metastasis were enhanced 2.9-fold by the presence of p95HER-2 (48.8% of node-negative versus 73.5% of node-positive patients; P = 0.03; odds ratio = 2.9). P95HER-2 was more frequent in metastatic lymph nodes than in primary tumors (45.7% versus 26.7%; P = 0.0009), whereas p185HER-2 overexpression was similar in both (22.3% versus 23.5%; P = 0.933). P95HER-2 did not significantly correlate with patient age, tumor size, stage, histotype, or hormone receptor status.
Conclusions: P95HER-2 in primary tumors was related to extent of lymph node involvement and was enhanced in nodal tissue suggesting an
important role as a marker or cause in breast cancer metastasis. Examination of the prognostic value of p95HER-2 in breast
cancer and its coexpression with metalloprotease activity seem warranted. |
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ISSN: | 1078-0432 1557-3265 |