Journal of Pathology and Translational Medicine

Original Articles

Clinicopathological Significance of Invasive Ductal Carcinoma with High Prevalence of CD44(+)/CD24(-/low) Tumor Cells in Breast Cancer.: Ji Youn Sung, Gou Young Kim, Yong Koo Park, Juhie Lee, Youn Wha Kim, Sung Jig Lim; Korean J Pathol. 2010;44(4):390-396.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.390

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BACKGROUND
Epithelial tumor cells with a CD44(+)/CD24(-/low) immunoprofile may have the ability to cause breast cancer. We studied these cells and their clinicopathological significance.
METHODS
The clinicopathologic findings of 100 invasive ductal carcinoma (IDC) cases and 45 ductal carcinoma in situ (DCIS) cases were reviewed. CD44(+)/CD24(-/low) tumor cells were identified by immunohistochemistry, and their clinicopathological implications in IDC and DCIS were analyzed.
RESULTS
IDC with a high prevalence of CD44(+)/CD24(-/low) tumor cells was significantly associated with larger mass, higher grade, estrogen receptor (ER) negativity, and tumor cells with a higher frequency of metastasis. The proportion of CD44(+)/CD24(-/low) tumor cells in IDC, and its DCIS components was not significantly different, whereas the proportion of CD44(+)/CD24(-/low) tumor cells was higher in DCIS than in the DCIS component of IDC (p < 0.001).
CONCLUSIONS
IDC with a high prevalence of CD44(+)/CD24(-/low) tumor cells might correlate with aggressive features, such as ER and higher grades. Moreover, the proportion of CD44(+)/CD24(-/low) tumor cells in the DCIS components of IDC and DCIS might harbor different biology, which may lead to differences in cancer progression and early carcinogenesis.

Citations

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Clinicopathologic Characteristics of Breast Cancer Stem Cells Identified on the Basis of Aldehyde Dehydrogenase 1 Expression
Yoon Seok Kim, Min Jung Jung, Dong Won Ryu, Chung Han Lee
Journal of Breast Cancer.2014; 17(2): 121. CrossRef
CD44/CD24 as potential prognostic markers in node-positive invasive ductal breast cancer patients treated with adjuvant chemotherapy
Agnieszka Adamczyk, Joanna A. Niemiec, Aleksandra Ambicka, Anna Mucha-Małecka, Jerzy Mituś, Janusz Ryś
Journal of Molecular Histology.2014; 45(1): 35. CrossRef

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 p53 and Rb Proteins in Invasive Ductal Carcinoma of the Breast.: Hyun Jin Son, Han Sang Yoon, Myoung Jae Kang; Korean J Pathol. 1999;33(6):443-449.

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Abstract PDF: Inactivation of tumor suppressor genes may play an important role in many human cancers including breast. This study was done to determine the relationship between the expression of p53 and Rb protein and prognostic factors such as histopathologic differentiation, tumor size, and lymph node metastasis. In 57 cases of breast invasive ductal carcinomas, the immunohistochemical staining with p53 and Rb protein gave the following results: p53 protein was detected in 45.6% (26/57) of cases. Tumors with large size, poor differentiation or lymph node metastases tended to show increased expression of p53 protein. However, p53 protein expression did not show any significant correlation with prognostic factors such as tumor size (p value 0.25), histologic grade (p value 0.75), and positive lymph node status (p value 0.26). Rb protein was detected in 57.9% (33/57) of cases. Rb protein also did not show any significant correlation with prognostic factors such as tumor size (p value 0.56), histologic grade (p value 0.71), and positive lymph node status (p value 0.98). There was no significant correlation between p53 expression and Rb protein expression (p value 0.80).

Expression of Maspin Protein in Ductal Hyperplasia, Intraductal Carcinoma and Invasive Ductal Carcinoma of the Breast.: Young Chae Chu, In Seo Park, Yoon Ju Kim, Joon Mee Kim, Hye Seung Han, Jee Young Han, Young Bae Kim; Korean J Pathol. 1999;33(8):614-619.

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Abstract PDF: Maspin is a recently described gene with tumor suppressor activity. The gene product is a 42 kD protein with homology to the serpin family of protease inhibitors and may play a role as an inhibitor of tumor cell invasion. The prior observation that invasive breast cancers and their metastases showed decreased maspin protein expression by immunostaining supports this speculation. However, the role of maspin in breast cancer progression has not been studied in detail. We, therefore, studied maspin protein expression in a series of hyperplasia, atypical ductal hyperplasia, intraductal carcinoma and invasive carcinomas. Immunohistochemical staining (IHC) for maspin was performed on paraffin sections of 136 breast specimens using a commercially available monoclonal antibody. Among the 106 cases studied were 36 moderate/florid ductal hyperplasia, 11 atypical ductal hyperplasia (ADH), 29 intraductal carcinoma (IDC) (4 low grade, 13 intermediate grade, 12 high grade) and 30 invasive ductal carcinomas. Thirty cases of normal breast were also studied as control group. IHC stains were scored using a semiquantitative scoring system. The mean IHC scores for maspin for normal, moderate/florid hyperplasia, atypical ductal hyperplasia, intraductal carcinoma, and invasive carcinoma were 5.51 1.30, 7.36 0.72, 3.82 1.60, 4.48 2.69, 3.97 3.30, respectively. These scores for each category were statistically significant (p<0.05), except between ADH and IDC. Maspin protein expression was increased in most cases of moderate/florid hyperplasia, while maspin expression was more heterogeneous in ADH and IDC. In high grade IDC, maspin protein expression was stronger than low and intermediate grade IDC, and this suggests the possibility of a compensatory cellular response against the forces driving further tumor progression. Two thirds of invasive ductal carcinomas expressed maspin protein weakly and focally. All metastatic carcinomas of lymph nodes were negative for maspin. It is possible that high grade IDC with strong maspin expression may represent a subset less likely to progress to invasive cancer. This speculation merits investigation in clinical outcome studies.

Association between the Expresson of MMP-2 and TIMP-2, and Growth Pattern of Tumor Border, Lymph Node Metastasis, and Estrogen Receptor in the Invasive Ductal Carcinoma of the Breast.: Soo Kee Min, Joon Mee Kim, Young Chae Chu, Young Up Cho, Bom Woo Yeom; Korean J Pathol. 2000;34(5):366-373.

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Abstract PDF: The most important prognostic factor of breast cancer is the status of lymph node or distant metastasis, which is resisted by basement membrane and stromal matrix. MMP (matrix metalloproteinase)-2 is a 72-kilodalton type IV collagenase/ gelatinase and degrades the type IV collagen which is a main component of the basement membrane. Therefore, MMP-2 is believed to be one of the key molecule for cancer invasion and metastasis. Enzymatic activity of MMP is inhibited by TIMPs (tissue inhibitors of metalloproteinase). TIMP-2 forms a complex with latent pro-MMP-2 and inhibits the active forms of MMP-2. The balance of MMPs and TIMPs is suspected as the important factor of invasion and metastasis of the tumor cells. We studied the association between the expression of MMP-2/TIMP-2 and growth pattern of tumor border, lymph node metastasis, and estrogen receptor expression in the 57 cases of invasive ductal carcinoma of the breast using immunohistochemical staining methods. The results revealed increased expression of MMP-2 in the infiltrating tumor border and tumors with positive lymph node metastasis and negative estrogen receptor with no statistical significance (p>0.05). But the expression of TIMP-2 was increased in expanding tumor border and tumors with positive lymph node metastasis and negative estrogen receptor without statistical significance (p>0.05).

Case Report

Fine Needle Aspiration Cytology of Invasive Ductal Carcinoma with Osteoclast-like Giant cells: A Case Report .: Eun Ha Jung, Hye Rim Park, Jin Hee Sohn; Korean J Cytopathol. 1998;9(2):221-226.

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Abstract PDF: Malignant tumors of the breast with stromal multinucleated giant cells are rare entity of uncertain clinical significance. There have been few reports on the fine needle aspiration cytologic(FNAC) findings about these rare tumors. We report a FNAC case of invasive mammary carcinoma with osteoclast-like giant cells not only for its rare occurrence but in particular for its distinctive cytologic picture on aspirated material. The patient was a 40-year-old woman who presented with a right breast mass for one month. Mammography showed a well-demarcated rounded mass density without calcification. The aspirates of FNAC were highly cellular and two main cell types were seen; malignant epithelial cells and osteoclast-like multinucleated giant cells. The carcinoma cells occurred singly or arranged in loose clusters with ill-defined cytoplasm, oval nuclei, coarse chromatin and small but distinct nucleoli. The multinucleated giant cells showed variable number of nuclei with prominent nucleoli and abundant dense oxyphilic cytoplasm. The immunocytochemical studies suggested that osteoclast-like giant cells were not of epithelial origin, but rather of histiocytic origin.

Original Articles

The Significance of Nuclear Size in Nuclear Grade of Invasive Ductal Carcinoma of the Breast.: Young Kyung Bae, Dong Sug Kim, Hye Jung Choi, Mi Jin Gu, Soo Jung Lee, Jea Young Lee; Korean J Cytopathol. 1999;10(1):21-26.

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Abstract PDF: To make the objective standard of nuclear size in grading nuclear pleomorphism of invasive ductal carcinoma of the breast, we measured maximal nuclear diameter of tumor cells on imprint cytology slides and histologic sections from 65 cases by using computer-based image analysis system(Optimas 6.0). The maximal diameter of red blood cells were also measured to evaluate the ratio of maximal nuclear diameter of tumor cells to maximal diameter of red blood cells. The mean values of maximal nuclear diameter of tumor cells on imprint cytology slides and histologic sections were 7.56 micrometer, 7.53 micrometer in nuclear grade 1, 8.92+/-0.98 micrometer, 9.02+/-0.74 micrometer in nuclear grade 2, and 12.90+/-1.47 micrometer, 12.44+/-1.41 micrometer in nuclear grade 3, respectively. There were no significant differences between values of imprint cytology and histologic section. The ratio of maximal nuclear diameter of tumor cells to maximal diameter of red blood cells were 1.3-1.4:1 in nuclear grade 1, 1.6-1.7:1 in nuclear grade 2, and 2.2-2.3:1 in nuclear grade 3. These values would be guidelines for grading nuclear pleomorphism of invasive ductal carcinoma of the breast on routine surgical pathology work.

Loss of PTEN Expression in Breast Cancers.: Sun Hee Chang, Shi Nae Lee, Min Sun Cho, Heasoo Koo, Woon Sup Han, Seock Ah Im, Byung In Moon, Hyun Suk Suh, Hye Young Choi, Sun Hee Sung; Korean J Pathol. 2005;39(4):236-241.

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Abstract PDF: Background
: PTEN, located on chromosome 10q23.31, is a novel tumor suppressor gene. In the sporadic breast cancers, the incidence of the loss of heterozygosity of PTEN is approximately 10% to 40%, but the incidence of intragenic mutation of PTEN is less than 1%. To as- sess the role of the PTEN in the invasive ductal breast cancer, we studied the frequency of the loss of PTEN expression, its correlation with the commonly used prognostic factors of the breast cancer and with PTEN promoter hypermethylation status. Methods : Immunohistochemical staining with an anti-PTEN protein antibody was performed on the paraffin-embedded breast tissues from 129 women with a diagnosis of invasive ductal carcinoma. Methylation specific PCR was performed to detect hypermethylation in the PTEN gene on the 28 cases with the loss of PTEN expression.
Results
: Sixty-two (48%) of 129 breast tumors had the loss of PTEN expression. The loss of PTEN expression was correlated with lymph node metastasis and stage, and there was a near-significant correlation with the tumor size. PTEN promoter hypermethylation was found in five (18%) out of 28 patients. Conclusion : These results suggest that the loss of PTEN expression might play a role in the progression of the breast cancer and that the aberrant promoter methylation is one of the silencing mechanisms of PTEN.

E-cadherin Expression Loss in T1 Invasive Ductal Carcinoma of the Breast as a Predictive Marker for Lymph Node Metastasis.: Eun Kyung Kim, Aysegul Sahin; Korean J Pathol. 2005;39(3):187-191.

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Abstract PDF: BACKGROUND
E-cadherin is a transmembrane glycoprotein, which has been shown to mediate calcium-dependent epithelial cell adhesion. A loss of E-cadherin expression has been associated with the tumor invasion and metastatic potential in some human cancers. The objective of this study was to evaluate E-cadherin expression in T1 breast ductal carcinomas in order to determine whether the loss of E-cadherin expression is correlated with lymph node metastasis.
METHODS
One hundred seventy nine patients with breast invasive ductal carcinoma, measuring less than 2 cm, were enrolled in this study. The subjects were divided into two groups on the basis of the status of the ipsilateral axillary lymph node, T1N1 (lymph node positive, n=91) or T1N0 (lymph node negative, n=88). None of the patients in this study had undergone preoperative chemotherapy. Formalin-fixed paraffin-embedded tissue sections of the primary breast cancers were stained by immunohistochemistry, using a mouse monoclonal antibody against E-cadherin. E-cadherin expression was designated as either positive (complete membranous staining) or negative (absent or incomplete membranous staining).
RESULTS
Benign breast parenchyma adjacent to invasive carcinoma was positive for E-cadherin. The loss of E-cadherin expression in the tumor was observed in 42% of patients of the T1N1 group, and in 24% of the T1N0 group. There was a significant correlation between the loss of E-cadherin expression and lymph node metastasis in the examined breast invasive ductal carcinomas (p=0.011).
CONCLUSIONS
Our findings suggest that E-cadherin is an important molecule with regard to both tumor cell adhesion and metastasis, and its absence may constitue an early event in metastatic development. Therefore, E-cadherin may be a useful predictive marker for nodal metastasis in patients suffering from invasive ductal carcinoma.

Case Report

Invasive Ductal Carcinoma Arising in a Recurrent Malignant Phyllodes Tumor: A Case Report.: Ahwon Lee, Gyeongsin Park, Kyo Young Lee, Chang Suk Kang, Byung Kee Kim, Sang In Shim; Korean J Pathol. 2005;39(2):134-136.

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Abstract PDF: We report here on a case of invasive ductal carcinoma arising in a recurrent malignant phyllodes tumor. The patient was a 33-year-old woman who presented with a left breast mass, and an excision was then performed. The mass, measuring 7.0 x 4.0 cm in size, was relatively well demarcated with a nodular contour and showed pale gray and solid cut surface with clefts on it. Histologically, the mass mainly consisted of stromal components that were characterized by high cellularity, marked nuclear atypism and brisk mitosis. The sparse glandular components were leaf-like in shape and lined by bland ductal epithelium without any nuclear atypism. Sixteen months later, the patient revisited our hospital with a recurrent mass, and underwent total mastectomy. The recurrent mass contained foci of definite invasive ductal carcinoma in the background of malignant phyllodes tumor, which was identical to the primary mass. This case demonstrates that it is possible that an invasive ductal carcinoma might arise within, at least with, a recurrent malignant phyllodes tumor.

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