title: Role of immunohistochemical detection of lymph-node metastases in management of breast cancer. International Breast Cancer Study Group.
abstract: BACKGROUND
  This study was designed to ascertain whether immunohistochemical methods could improve the detection of metastases in primary breast-cancer patients whose axillary lymph nodes were classified, by conventional methods, as disease free.
  
  
  METHODS
  Ipsilateral lymph nodes (negative for metastases by routine histology) from 736 patients (participants in Trial V of the International [Ludwig] Breast Cancer Study) were examined by serial sectioning and staining with haematoxylin and eosin (two sections from each of six levels) and by immunohistochemistry of a single section (with two anticytokeratins AE-1 and CAM 5.2). After median follow-up of 12 years, disease-free and overall survival were estimated by Kaplan-Meier methods.
  
  
  RESULTS
  Occult nodal metastases were detected by serial sectioning and haematoxylin and eosin in 52 (7%) of 736 patients and by immunohistochemistry in 148 (20%). Only two (3%) of 64 invasive lobular or mixed invasive lobular and ductal cancers had node micrometastases, detected by haematoxylin and eosin, compared with 25 (39%) by immunohistochemistry. Occult metastases, detected by either method, were associated with significantly poor disease-free and overall survival in postmenopausal but not in premenopausal patients. Immunohistochemically detected occult lymph-node metastases remained an independent and highly significant predictor of recurrence even after control for tumour grade, tumour size, oestrogen-receptor status, vascular invasion, and treatment assignment (hazard ratio 1.79 [95% CI 1.17-2.74], p=0.007).
  
  
  CONCLUSIONS
  The immunohistochemical examination of ipsilateral axillary lymph nodes is a reliable, prognostically valuable, and simple method for the detection of occult nodal metastases. Immunohistochemistry is recommended as a standard method of node examination in postmenopausal patients.
authors.affiliation: Department of Pathology, USC School of Medicine, Norris Cancer Center, Los Angeles, CA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Cote
authors.forename: H F
authors.initials: HF
authors.lastname: Peterson
authors.forename: B
authors.initials: B
authors.lastname: Chaiwun
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: M
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: B
authors.initials: B
authors.lastname: Gusterson
authors.forename: A M
authors.initials: AM
authors.lastname: Neville
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D007633:Keratins