title: NH(2)-terminal truncated HER-2 protein but not full-length receptor is associated with nodal metastasis in human breast cancer.
abstract: 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.
authors.affiliation: Laboratory of Oncology Research, Medical Oncology Service, Vall d'Hebron Hospital, 08035 Barcelona, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Molina
authors.forename: Rosana
authors.initials: R
authors.lastname: Sáez
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Ramsey
authors.forename: María-José
authors.initials: MJ
authors.lastname: Garcia-Barchino
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Evans
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Keenan
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Javier
authors.initials: J
authors.lastname: García-Conde
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Gail M
authors.initials: GM
authors.lastname: Clinton
mesh_terms: 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
chemical_list: D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases