Journal of Pathology and Translational Medicine

Original Articles

c-erbB-2 Oncoprotein Expression in Ductal Carcinoma in situ and Paget's Disease of the Breast.: Jung Yeon Kim, Kyung Ja Cho, Seung Sook Lee, Shin Kwang Khang, Nam Sun Paik; Korean J Pathol. 1996;30(11):972-980.

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Abstract PDF: A clinico-pathologic study with an immunohistochemical examination for c-erbB-2 expression in 54 cases of ductal carcinoma in situ and 16 cases of Paget's disease of the breast was performed. c-erbB-2 oncoprotein overexpression was observed in 45% (24/54) and 88% (14/16) of ductal carcinoma in situ and Paget's disease, respectively. The overexpression of c-erbB-2 oncoprotein was significantly correlated with the nuclear grade of tumors and inversely with the status of the estrogen receptor. c-erbB-2 was positive in 4 out of 5 patients with metastasis to axillary lymph nodes and 3 out of 4 patients who died of the disease. Prognostic significance of c-erbB-2 oncoprotein in ductal carcinoma in situ was highly suggested. The expression of c-erbB-2 oncoprotein in Paget's disease was well correlated with coexisting infiltrating or in situ ductal carcinoma. The high positive rate of c-erbB-2 oncoprotein in ductal carcinoma with Paget's disease could be understood with a recent hypothesis that c-erbB-2 oncoprotein is involved in promotion of cell motility and the spread of carcinoma cells.

Ductal Carcinoma In Situ of the Breast: Comparison of Histologic Classifications and Correlation with Histologic Grade of Coexisting Invasive Ductal Carcinoma.: Sung Ran Hong, Yee Jeong Kim, Yi Kyeong Chun, Hye Sun Kim, Hy Sook Kim; Korean J Pathol. 1999;33(6):434-442.

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Abstract PDF: Recently developed new classifications (Holland, Van Nuys, modified Lagios) of ductal carcinoma in situ (DCIS) linked to outcome have emphasized the importance of nuclear morphology rather than architecture. We have evaluated these three classifications in ductal carcinomas composed of in situ and invasive carcinomas. The reproducibility of three classifications was assessed (n=49), and the histological grade of the DCIS was compared with the histologic differentiation (modified Bloom & Richardson method) and nuclear grade (modified Black method) of the coexisting invasive ductal carcinoma (n=45). According to Holland classification, the DCIS component was poorly differentiated in 51.0%, intermediately differentiated in 40.8%, and well differentiated in 8.2%. Using the Van Nuys classification, the DCIS component was group 3 (high grade with or without necrosis) in 44.9%, group 2 (non-high grade with necrosis) in 28.6%, and group 1 (non-high grade without necrosis) in 26.5%. According to the modified Lagios classification, the DCIS component was high-grade in 42.8%, intermediate-grade in 32.7%, and low-grade in 24.5%. The histologic grades of the three classifications revealed significant correlations between Holland and Van Nuys classification (p<0.0001) and between Holland and modified Lagios classification (p<0.0001), especially in poorly differentiated/group 3/high-grade DCIS. The reproducibility of classification of the DCIS was 71.4% in the Holland, 61.2% in the Van Nuys, and 55.1% in the modified Lagios classifications. The grade of the DCIS showed significant correlation with the grade of coexisting invasive ductal carcinoma (p<0.0001), especially in poorly differentiated/group 3/high-grade DCIS. In conclusion, DCIS grade, determined by the Holland, Van Nuys or modified Lagios classifications, is closely correlated with the histologic grade of the invasive ductal component in tumors composed of in situ and invasive ductal carcinoma, and may be a useful factor to estimate clinical behavior of DCIS. In our experience the Holland classification is recommended for DCIS classification due to its high reproducibility.

Expression of p27kip1, Cyclin D1 and p53 Protein in Ductal Carcinoma In Situ of the Breast.: Young Lyun Oh, Sang Yong Song, Jong Sun Choi, Young Hyeh Ko, Hwoe J Ree, Geung Hwan Ahn; Korean J Pathol. 1999;33(9):709-716.

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Abstract PDF: p27(kip1) protein, a cyclin-dependent kinase inhibitor, has been reported to be a powerful negative prognostic marker in patients with breast carcinoma. However, to this day, studies on p27(kip1) protein expression in ductal carcinoma in situ (DCIS) have been extremely limited. We studied the immunohistochemical expression of p27(kip1) protein in 49 cases of the DCIS and compared the findings to the clinicopathologic parameters, cyclin D1, p53 and estrogen receptor (ER). Positive nuclear staining of p27(kip1) protein was identified in 23 (46.9%) cases. The p27(kip1) protein expression correlated positively with the cyclin D1 immunopositivity (p<0.005) and ER expression (p<0.005). No significant associations were seen in the p27(kip1) protein expression and clinicopathologic parameters. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with ER expression (p<0.001). The p53 protein expression was identified in 30.6% and seemed to be correlated inversely with ER expression (p=0.06). The DCISs with high grade nuclei were more likely to be p53-positive (p<0.05). Our data suggest that the expression of p27(kip1) protein as well as cyclin D1 and p53 protein may be influenced by the ER status in DCIS. The significantly positive correlation of p27(kip1) protein and cyclin D1 expression (p<0.005) supports the theory that the balance of the two opposing signals is important in determining the cell proliferation in breast cancers. Therefore, a comprehensive understanding of loop reaction of p27(kip1)-cyclin D1-ER may be necessary for the treatment of DCIS.

Expression of Biologic Markers and DNA Ploidy Analysis in Atypical Ductal Hyperplasia and Ductal Carcinoma in Situ of the Breast.: Hee Jung Kim, Woo Hee Jung, Hyeon Joo Jeong, Hy De Lee; Korean J Pathol. 1999;33(11):1076-1089.

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Abstract PDF: Status of margins and the size of the lesion are independent prognostic factors of ductal carcinoma in situ (DCIS). Histologic grading of DCIS and expression of biologic marker also appear to act as prognostic factors. However, DNA ploidy analysis using flow cytometry in the DCIS and atypical ductal hyperplasia (ADH) has been rarely reported, and the biologic behavior of ADH is unknown. We performed immunohistochemical staining and DNA ploidy analysis using flow cytometry on 45 cases of pure DCIS without microinvasion and 34 cases of ADH to compare the expression of biologic markers and DNA ploidy patterns according to the histologic grade of DCIS, to evaluate the usefulness of the Van Nuys classification, and to investigate the biologic behavior of ADH and low grade DCIS. A total of 41.9% of DCIS and 32.1% of ADH were detected mammographically in asymptomatic patients. The most common subtype of the high grade DCIS was comedo type (56.3%), while the low and intermediate grade DCIS were cribriform type. Expression of ER, c-erbB-2 and Ki-67 proliferative index (PI) was significantly associated with nuclear grade and histologic grade of DCIS. Expression of c-erbB-2 was also significantly correlated with presence of necrosis. In low grade DCIS, Ki-67 PI was significantly higher than ADH. A total of 63.6% of DCIS and 70% of ADH were diploidy and 15.9% of DCIS was aneuploidy. There was no aneuploidy in ADH. No significant association was noted between DNA ploidy and histologic grade or nuclear grade. However, in high grade DCIS, the frequency of aneuploidy was high. In conclusion, histologic grading of DCIS employing nuclear grade and necrosis is a useful tool accounting for biologic behavior. High grade DCIS and comedo DCIS impart aggressive biologic behavior and suggest a higher possibility of local recurrence or progression to invasive carcinoma. In the differential diagnosis of ADH and low grade DCIS, the use of Ki-67 PI and DNA ploidy analysis by flow cytometry will be helpful for accurate diagnosis and prediction of biologic behavior.

Expression of p53 Protein and Ki-67 in Atypical Ductal Hyperplasia, Ductal Carcinoma in Situ, and Microinvasive Ductal Carcinoma of the Breast.: Yi Kyeong Chun, Hye Sun Kim, Yee Jeong Kim, Sung Ran Hong, Hy Sook Kim, Byung Jun Park, Sung Su Kang, Ji Hyun Lee, Sung Kong Lee, Sun Hee Sung, Woon Sup Han; Korean J Pathol. 2000;34(9):665-672.

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Abstract PDF: Mutation of the p53 gene is one of the most common genetic alterations in invasive breast carcinoma. However, it is unclear that the mutation usually occurs in noninvasive breast lesions. It might be expected that there is a correlation between histologic progression of breast lesions and proliferative rate. We investigated the expression of p53 protein and Ki-67 labelling index (LI) using immunohistochemistry in 16 ductal carcinoma in situ with microinvasion (DCIS-Mi), 56 DCIS, 15 atypical ductal hyperplasia (ADH), and 7 intraductal hyperplasia (IDH). Expression of p53 protein was detected in 33.9% of DCIS and 56.3% of DCIS-Mi and was confined exclusively in Van Nuys DCIS group 2 and 3. In ADH and IDH, no expression of p53 protein was found. There was no significant correlation between Van Nuys DCIS groups and Ki-67 LI. In conclusion, p53 mutation may be involved in the neoplastic progression from ADH to DCIS and is directly related to high nuclear grade and associated necrosis of DCIS.

Case Report

Invasive Lobular Carcinoma of the Breast Associated with Mixed Lobular and Ductal Carcinoma In Situ: A Case Report.: Ji Shin Lee, Hyung Seok Kim, Jong Jae Jung, Young Bog Kim, Dong Sug Kim; Korean J Pathol. 2001;35(1):89-91.

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Abstract PDF: Mixed lobular and ductal carcinoma in situ is very rare. We recently experienced a case of invasive lobular carcinoma associated with mixed lobular and ductal carcinoma in situ in a 50-year-old female. The infiltrating portions of lobular carcinoma revealed thread-like strands of tumor cells. Lobular carcinoma in situ with pagetoid spread into the ducts and ductal carcinoma in situ of the predominantly papillary type were also noted in the same mass.

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