title: The predictive power of semiquantitative immunohistochemical assessment of p53 and c-erb B-2 in lymph node-negative breast cancer.
abstract: A series of 107 lymph node-negative (LNN) breast cancers was stained immunohistochemically with a combination of p53 and c-erb B-2. The immunohistochemical results were semiquantitated using a previously described system by Allred et al. p53 immunopositive cases were further screened for DNA mutations by the polymerase chain reaction-single-strand conformation polymorphism method (PCR-SSCP). Three representative cases showing mobility shifts were directly sequenced. One hundred of 103 invasive carcinomas were of no special type (infiltrating ductal carcinomas not otherwise specified). The three special type carcinomas included a tubular carcinoma, a classic infiltrating lobular carcinoma, and a mucinous carcinoma. Twenty-six patients (25.2%) had grade I carcinomas, and 77 patients (75%) had grade 2 or 3 carcinomas. There were four cases composed predominantly of ductal carcinoma in situ (DCIS) with foci of microinvasion. Twenty-seven of 107 patients (25%) died of disease. All those who died had grade 2 or 3 tumors. Univariate analysis showed that p53 and c-erb B-2 positivity (score > 6) were associated with a decreased overall survival (OS) (P = .0012 and P = .010, respectively), and a decreased disease-free survival (DFS) (P = .0009 and P = .027, respectively). The multivariate model selected these two variables as the best predictors of both OS and DFS (all P = or < .01). These results suggest that semiquantitative immunohistochemical analysis of p53 and c-erb B-2 provides prognostic information in LNN disease.
authors.affiliation: Department of Pathology, Victoria Hospital, London Regional Cancer Centre, Ontario, Canada.
authors.forename: F P
authors.initials: FP
authors.lastname: O'Malley
authors.forename: Z
authors.initials: Z
authors.lastname: Saad
authors.forename: N
authors.initials: N
authors.lastname: Kerkvliet
authors.forename: G
authors.initials: G
authors.lastname: Doig
authors.forename: L
authors.initials: L
authors.lastname: Stitt
authors.forename: P
authors.initials: P
authors.lastname: Ainsworth
authors.forename: H
authors.initials: H
authors.lastname: Hundal
authors.forename: A F
authors.initials: AF
authors.lastname: Chambers
authors.forename: D I
authors.initials: DI
authors.lastname: Turnbull
authors.forename: V
authors.initials: V
authors.lastname: Bramwell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53