Histopathologic Analysis of BI-RADS Category 4a Breast Lesions Diagnosed by Ultrasonography / 한국유방암학회지

PURPOSE: We analyzed the histopathologic findings of the patients with ultrasongraphic Breast Imaging Reporting and Data System (BI-RADS) Category 4a breast lesions to determine which patient can be excluded from any invasive, diagnostic procedure in the future. METHODS: Of the 180 cases of BI-RADS Category 4a breast lesions that were diagnosed with ultrasonography during a 6 month-period, 132 cases were pathologically confirmed and these were analyzed retrospectively. Four benign cases that did not undergo any further procedure after fine needle biopsy and 6 malignant cases (4.5%) were excluded from this study. RESULTS: Of the 122 cases, 77 cases (63.1%) showed homogeneous benign finding, and 45 cases (36.9%) showed heterogeneous finding that was made up of two or more different pathologic lesions. Fibroadenoma (55.8%) was the most frequent pathologic finding in the cases with homogeneous finding, followed by fibrocystic change (14.3%), and fibrosis (7.8%). The cases with heterogeneous finding presented fibrocystic change (55.5%), microcalcification (48.8%), ductal hyperplasia (42.2%), and fibroadenoma (31.1%) in the order of frequency. CONCLUSION: Lesion with heterogeneous histopathologic nature was the most frequent finding defined as category 4a in breast ultrasonography, followed by fibrodenoma, fibrocystic change, microcalcification, and ductal hyperplasia. Refining more specific ultrasonographic findings of these lesions would guarantee that radiologists exclude more benign lesions from category 4a.

Heterogeneity of Invasive Ductal Carcinoma: Proposal for a Hypothetical Classification

To investigate what heterogeneity exists in breast cancer, 228 consecutive patients with operable invasive duetal carcinoma (IDC), not otherwise specified, were categorized on the basis of the horizontal progression model of carcinogenesis. Using the reversed Black's nuclear grade (RBNG) in the IDC component and the association of ductal carcinoma in situ (DCIS), the patients were classified into pure IDC (IDC de novo or ab initio) as Group I, non-high grade (RBNG 1 and 2) IDC with DCIS as Group II, and high grade (RBNG 3) IDC with DCIS as Group III. The Groups classified in the present study appeared as a prognostic factor independent of known prognostic and predictive factors in multivariate test. Group I had the worst prognosis among the three groups and was the most non-responsive to tamoxifen. After performing stratifying analyses by group, it was found that metastasis-free survival was statistically associated with the status of hormone receptors estrogen receptor and progesterone receptor and tamoxifen therapy only in Group II. In addition, the status of c-erbB-2 expression had prognostic significance only within the Group III. Our results may be used to frame an alternative hypothetical model for breast cancer evolution and will lead us to reconsider the tailoring of the comprehensive therapeutic modality used at the present time.

Expression of the Markers for the Mammary Stem Cells and the Cellular Lineages of the Mammary Gland on Ductal Carcinoma In Situ / 한국유방암학회지

PURPOSE: Breast Cancer is an inter-tumoral and intra-tumoral heterogeneous disease. It remains unclear whether this heterogeneity results from different target cells or from different subsets of genetic abnormalities, otherwise from both. We postulated that in addition to genetic cloning, a variety of cells that exist during the defined developmental stages of the human mammary gland could give rise to the heterogeneity of breast cancer. To verify this postulation, we have analyzed pure ductal carcinoma in situ (DCIS) for the expression of the biomarkers that represent the mammary stem cell, the early progenitor cells, and the glandular and myoepithelial cells of the mammary gland. METHODS: We investigated the relationship between the immnuohistochemical expression of the mammary development-associated biomarkers {cytokeratin-18 (CK18), cytokeratin-6 (CK6), alpha-smooth muscle actin (SMA), Wnt-1, Notch 3} and some other factors {the menopausal status, the estrogen receptor (ER) status, the progesterone receptor (PR) status, c-erbB-2, and the number of tumor foci} in 26 cases of DCIS. RESULTS: All 26 cases included in this study showed the positive expressions of CK18 and SMA. The expression of all the markers was not correlated with the menopausal status. The positive expression of CK6 had a statistically significant relationship with a negative estrogen receptor (p=0.014), positive c-erbB-2 (p=0.048), high nuclear grade (p=0.001), and single focus of DCIS (p=0.017). The expression of Wnt-1 and Notch 3 did not have significant correlation with any factors. However, the positive expression of Wnt-1 showed a tendency of a negative ER (p=0.061) and the positive expression of Notch 3 also showed a tendency of a negative ER (p=0.086) and a high nuclear grade (p=0.086). CONCLUSION: The CK6 positive tumor is thought to originate from the more primitive cells compared to the CK6 negative tumor. Unifocality of the CK positive tumor might result from the arrest of differentiation of the original cell after disease affection. DCISs could be categorized into the CK6 positive and negative groups.

Cathepsin D expression in the tumor cells and juxta-tumoral stromal cells of T1 invasive ductal carcinoma, Nos / 한국유방암학회지

INTRODUCTION: Cathepsin D (CD) is a lysosomal protease that can be used as an important prognostic cytosolic factor for breast cancer. Its over-expression in breast cancer cells and in the host stromal cells in the tumor has been proposed as being a poor prognostic indicator. However, its prognostic value is still being debated. Therefore, CD expression needs to be examined in more relevant subsets of tissue in order to refine its prognostic significance and the clinical applications. METHODS: Regardless of the lymph node status, 110 T1 invasive ductal carcinomas of the breast were immunohistochemically evaluated for the CD expression using rabbit anti-cathepsin D monoclonal antibody. This study separately assessed the expression of CD in the invasive component (IDC), in the in situ component (DCIS), and in the juxtatumoral stromal cells (JTSC). The CD expression level in these three kinds of tissues were correlated with the nuclear grade, ER, PR, c-erb-B2, p53, the N stage, the T stage, and the 5 year metastasis-free survival. RESULTS: Positive CD expression in the JTSC was associated with the T stage (p = 0.001) and the N stage (p = 0.029), whereas positive CD expression in the DCIS and IDC was not. In addition, strong CD expression in the JTSC correlated with the nuclear grade of the invasive component (p = 0.024). In all three components, no statistically significant correlation was found between the biomarker (ER, PR, cerb-B2, p53) and the CD expression. On univariate analysis, positive expression in the JTSC was correlated with a poor 5 year- metastasis free survival (p = 0.007), but the positive expression in the IDC and DCIS was not. CONCLUSION: CD expression of the JTSC could represent the N stage, the T stage, and the nuclear grade of T1 IDC. Whether or not it would have an independent influence on the prognosis of T1 IDC, CD expression in the JTSC is probably an indicator of the tumor virulence. CD expression in the JTSC will provide an important clue for the development of new CD targeted therapies, and it will serve as an important criterion for selecting the appropriate candidates for these future targeted therapies.

Clinical Features of Invasive Ductal Carcinoma According to Histopathologic Classification

PURPOSE: Of the hypothetical models of the carcinogenesis of breast cancer, the horizontal progression is most acceptable at the present time. According to the hypothesis, there are genetically different pathways among pure invasive ductal carcinoma (IDC), non-high grade IDC with ductal carcinoma in situ (DCIS), and high grade IDC with DCIS. The purpose of this study is to determine if there is any heterogeneity in biological behavior among these three categories. METHODS: With reversed Black nuclear grade (RBNG) in IDC component and the association of DCIS, we divided 184 breast cancer patients, who had underwent curative operations, into three groups. The patients with pure IDC were included in Group 1, non-high grade (RBNG 1 and 2) IDC with DCIS in Group 2, and high grade (RBNG 3) IDC with DCIS in Group 3. And we retrospectively analyzed and compared three groups with mean age, menopausal status, T stage, N stage, the expression rate of ER, PR, p53, and c-erbB-2, and cumulative metastasis-free survival. RESULTS: The percentage of the postmenopausal patients was significantly smaller in Group 3 (14.0%, P=0.025) than Group 1 and 2 (36.1% and 30.6%). There were significantly higher expression rates of ER and PR in Group 2 with 78.3% and 68.3%, respectively (P=0.000 and P=0.030). The 5-year metastasis- free survival rate were 70.4% in Group 1, 85.2% in Group 3, and 87.5% in Group 2. The Log Rank test in Kaplan-Meier cumulative survival curve showed the statistically significant differences among three groups (P= 0.041). CONCLUSION: We can say that there would be clinical heterogeneity among three groups classified by histopathologic findings. To apply this classification to the multi-disciplinary therapeutic modality of breast cancer, further study using a new biologic marker, which is associated with invasiveness and metastagenicity and can discrminate the three categories of breast cancers in any kind of specimen biopised preoperatively, is needed.