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Molecular Oncology, Markers, Clinical Correlates |
Laboratory of Oncology Research, Medical Oncology Service, Vall d’Hebron Hospital, 08035 Barcelona, Spain [M. A. M., J. A., J. B.]; Hematology and Medical Oncology Service, Hospital Clínico, 46010 Valencia, Spain [R. S., M-J. G-B., A. L., J. G-C.]; and Departments of Physiology and Pharmacology [E. E. R., E. J. K.] and Biochemistry and Molecular Biology [A. J. E., G. M. C.], Oregon Health Sciences University, Portland, Oregon 97201
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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