Clinical Relevance of Clinicopathologic Parameters and Tumor Markers in Ductal Carcinoma in Site of the Breast

Kim, Hyun Chul; Song, Eun Young; Jung, Soo Gin; Yoon, Hye Kyung; Lee, Jin Yong

Abstract

PURPOSE
Ductal carcinoma in situ (DCIS) of the breasts is a heterogeneous group of lesions with diverse malignant potentials and controversial treatment options. This study was planned to investigate the patterns of clinicopathologic parameters and tumor markers related to biological aggressiveness and to make treatment decisions available based on a variety of these parameters. METHODS: We reviewed forty cases of DCIS treated at Pusan Paik Hospital from March 1992 to July 2002. Clinicopathologic features such as age, chief complaint, mammographic finding, tumor size, histologic subtype, and operation type were analysed, and the expression of ER, PR, p53, C- erbB-2, cathepsin D, bcl-2, MIB-1 and CD34 were evaluated using immunohistochemical methods. RESULTS: The size of the tumor was less than 1.5 cm in 16 (44.4%) cases, 1.5 cm to 4 cm in 17 (47.2%) cases, and more than 4 cm in 3 (8.3%) cases. There were 11 (27.5%) cases of the comedo subtype and 29 (72.5%) cases of the noncomedo subtype. Nuclear grade was divided into low (8 cases, 20.0%), intermediate (20 cases, 50.0%), and high (12 cases, 30.0%). According to Van Nuys' classification, there were 25 (62.5%) cases, 4 (10.0%) cases, and 11 (27.5%) cases of group I, II, and III, respectively. The groups presenting as mass on mammogram had no significant relationship with those presenting as microcalcification in terms of tumor size, histologic subtype, nuclear grade, and Van Nuys classification. The expression rates of PR, p53, C-erbB-2, cathepsin D, and bcl-2 were 32.4%, 67.6%, 35.1%, 29.7%, 67.6%, and 45.9%, respectively. High MIB-1 labelling index (LI) and high microvessel density were observed in 8.1% and 32.4%, respectively. The group presenting as mass on mammogram showed higher ER (P=0.0276) and PR (P=0.102) expression, compared with the microcalcification group. Positive ER and PR were associated with low nuclear grade (P=0.0233, 0.1727), while positive p53 and C-erbB-2 and high MIB-1 LI correlated with Van Nuys' group III (P=0.0637, 0.0532). Positive ER correlated with positive PR (P=0.0581) and negative C-erbB-2 (P=0.0642). In addition, there were positive associations between PR and bcl-2 expression (P=0.0939), between p53, C-erbB-2 (P<0.0001) and high MIB-1 labelling index (P= 0.0785), and between cathepsin D and high microvessel density (P= 0.0151). CONCLUSION: Clinico-pathologic evaluation of tumor size, histologic subtype, nuclear grade, and Van Nuys classification can help predict more aggressive immunophenotypes of DCIS. Positive p53 and C-erbB-2 and high MIB-1 is associated not only with more aggressive clinical behavior and more advanced histologic features of DCIS, but also with negative ER, PR, and bcl-2. Our results support the clinical relevance of combining both clinico-pathologic factors and biologic tumor markers for determining the treatment modality in DCIS patients.