Biologic Markers in Ductal Carcinoma In Situ and Concurrent Infiltrating Carcinoma

Abstract

The relevance of 8 contemporary classification and grading systems for ductal carcinoma in situ (DCIS) of the breast was examined in 100 tumors by comparing DCIS grade with grade of the concurrent infiltrating ductal carcinoma (IDC). Besides tumor size and nodal status, the immunohistochemical parameters in both lesions were compared, including estrogen receptor, progesterone receptor, c-erbB-2 protein, E-cadherin, vimentin, Ki-67 (MIB1), and p27. Nuclear grading of DCIS alone or in combination with architectural pattern and necrosis showed the best correlation with grade of the invasive component. There also was a positive correlation between every biologic marker expressed in DCIS and in the concurrent IDC, supporting a clonal relationship. Biologic markers varied between the different grades of DCIS. DCIS is heterogeneous, and the progression of DCIS to IDC may be from low-grade DCIS to low-grade IDC and high-grade DCIS to high-grade IDC. This concept is different from the conventional model held for intraepithelial neoplasia in the cervix, vulva, vagina, and skin, in which there is increasing severity of in situ atypia (dysplasia) before the development of stromal invasion.

Quantitative analysis of estrogen receptor heterogeneity in breast cancer

“…These confounding factors were minimized because, as described above, analysis was limited as much as possible to previously identified areas of invasive cancer, and because adjacent in situ tumors typically show similar ER expression compared with the invasive component. 15 In addition, a number of investigators have described more intense staining in the periphery of tumors compared with the center. 16 This can be attributed in part to increased necrosis in the center (these areas are eliminated from AQUA analysis with a crop function) and fixation artifact.…”

Evaluation of pathways for progression of heterogeneous breast tumors

“…The clinical observations that were used in this study reported the number of specimens that were classified as ductal carcinoma in situ (DCIS) grade 1, 2, or 3, and in addition, invasive ductal carcinoma (IDC) grade 1, 2, or 3, for a total of nine possible co-occurrence frequencies (Gupta et al, 1997;Cadman et al, 1997;Leong et al, 2001). The observed co-occurrence matrices have a pattern.…”

“…These pathways were based, in part, on reports of chromosome or protein changes in various grades of DCIS and IDC. Measuring protein expression patterns, Leong et al (2001) and Mommers et al (2001b) proposed that atypical hyperplasia could progress to grades DCIS, and then each grade of DCIS could progress to the corresponding grade of IDC. Roylance et al (1999) concluded that there was not progression from welldifferentiated tumors to poorly differentiated tumors, based on chromosome region losses and gains determined by comparative genomic hybridization.…”

“…It is important to able to predict how a tumor will progress, since this may influence treatment decisions. Several pathways describing the relationship between grades of DCIS and grades of IDC have been proposed (Buerger et al, 1999;Gupta et al, 1997;Leong et al, 2001;Mommers et al, 2001b;Roylance et al, 1999Roylance et al, , 2002. However, it is not clear which pathway best describes the biological relationship between grades of DCIS and IDC.…”

Molecular Grading of Ductal Carcinoma In situ of the Breast

“…13). The histopathologic grade of invasive cancer coexisting with DCIS fulfills these criteria on the basis that (a) the biology of DCIS and concomitant invasive breast cancer are closely related as evidenced by strongly concordant expression of biological indicators (14); (b) the biology of invasive cancer is reflected by histopathologic grade (15); and (c) grade is correlated with survival (16).…”