NH(2)-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 characterized.


OBJECTIVE
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.


METHODS
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.
Molina
Miguel A
MA
Laboratory of Oncology Research, Medical Oncology Service, Vall d'Hebron Hospital, 08035 Barcelona, Spain.
Sáez
Rosana
R
Ramsey
Elizabeth E
EE
Garcia-Barchino
María-José
MJ
Rojo
Federico
F
Evans
Adam J
AJ
Albanell
Joan
J
Keenan
Edward J
EJ
Lluch
Ana
A
García-Conde
Javier
J
Baselga
José
J
Clinton
Gail M
GM
D000368:Aged; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008024:Ligands; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000737:chemistry*; D012307:Risk Factors; D014407:Tumor Cells, Cultured
D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases