The prognostic significance of multiple morphologic features and biologic markers in ductal carcinoma in situ of the breast

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 Ͼ 3.5% and bcl-2 Ͻ 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.

Prognostic markers and long-term outcomes in ductal carcinoma in situ of the breast treated with excision alone

“…Tumor size was divided into 2 categories (category 0, 15 mm; category 1, >15 mm) that were consistent with the categories used in the previous study, which were derived from the Van Nuys prognostic index. 14,16 Histopathological Features The data for the patients from the original study were collected via review of glass slides. 16 For the new patients, histopathological and immunohistochemical tumor information were obtained through review of pathology reports.…”

“…14,16 Histopathological Features The data for the patients from the original study were collected via review of glass slides. 16 For the new patients, histopathological and immunohistochemical tumor information were obtained through review of pathology reports. The specimens were originally signed out by Thomas Jefferson University Hospital pathologists, and many were reviewed by one of the authors (J.P.P.).…”

“…Immunohistochemical studies were performed as described in the previous study. 16 p21, and p53 were not evaluated on new patients, but were reevaluated as markers in the original cases. 16 All immunohistochemical stains were accompanied by positive and negative controls, which were within acceptable ranges.…”

“…16 p21, and p53 were not evaluated on new patients, but were reevaluated as markers in the original cases. 16 All immunohistochemical stains were accompanied by positive and negative controls, which were within acceptable ranges. The percentage of positive cells in the tumor population was determined manually, and only nuclear staining was considered positive in the evaluation of ER and PR.…”

“…Estrogen receptor (ER) and progesterone receptor (PR) were among the first markers studied in breast cancer and have been evaluated in DCIS. 9,16,17 Research on marker status in DCIS has shown hormone receptor status to be more effective as a predictor of response to treatment than as a predictor of time to recurrence. 9, 10 Balleine et al 10 established a binary molecular grading scheme for DCIS in 2008 based on nuclear grade and Ki-67 score.…”