title: The prognostic significance of multiple morphologic features and biologic markers in ductal carcinoma in situ of the breast: a study of a large cohort of patients treated with surgery alone.
abstract: BACKGROUND
  A number of conventional histopathologic features have been associated with recurrence of ductal carcinoma in situ (DCIS) after surgery alone and are included in the Van Nuys Pathologic Classification and Prognostic Index. To the authors' knowledge, very little is known regarding the prognostic significance of the many biologic markers that have been studied in DCIS in the past decade.
  
  
  METHODS
  Clinical and pathologic data were analyzed from 151 patients who underwent wide local excision alone for DCIS that was diagnosed by mammography or as an incidental finding between 1982 and 2000. Using local disease recurrence as an endpoint, the authors sought to determine the prognostic significance of a large number of histopathologic parameters as well as biologic markers (estrogen receptor [ER], progesterone receptor [PR], p53, HER-2/neu, Ki-67, p21, and bcl-2), as determined by immunohistochemical staining of contemporary or archival tissue.
  
  
  RESULTS
  With a median follow-up of 65 months, 42 recurrences were reported to occur between 11 months and 97 months after definitive surgery. In a univariate analysis, tumor size, Van Nuys pathologic classification, and degree of necrosis demonstrated significant correlations with the rate of recurrence. Tumor size, necrosis, nuclear grade, and comedonecrosis were found to be associated significantly with the time to disease recurrence. None of the biologic markers demonstrated a significant association with the rate of recurrence or the time to disease recurrence. In a multivariate analysis, only large tumor size (Van Nuys 2 or 3) and higher degrees of necrosis (Van Nuys 2 or 3) were found to be associated significantly with both the rate of recurrence and the time to recurrence. No biologic marker showed a significant correlation with recurrence. Using Classification and Regression-Tree Analysis and Tree-Structured Survival Analysis, PR > 3.5% and bcl-2 < 97.5% were associated with a higher recurrence rate in the subgroup of patients with small tumor size (Van Nuys size 1) and higher degrees of tumor necrosis (Van Nuys 2 or 3).
  
  
  CONCLUSIONS
  The current results confirmed the value of conventional histopathologic parameters, as outlined in the Van Nuys classification system, in predicting local recurrence of DCIS. Using traditional logistic analyses, no significant correlation was found between a variety of biologic markers and disease recurrence.
authors.affiliation: Department of Pathology, Health Network Laboratories/Lehigh Valley Hospital, Allentown, Pennsylvania 18103, USA. cornf1@dca.net
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Cornfield
authors.forename: Juan P
authors.initials: JP
authors.lastname: Palazzo
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Schwartz
authors.forename: Shanth A
authors.initials: SA
authors.lastname: Goonewardene
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Kovatich
authors.forename: Inna
authors.initials: I
authors.lastname: Chervoneva
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: Roland
authors.initials: R
authors.lastname: Schwarting
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015331:Cohort Studies; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human