Journal of Pathology and Translational Medicine

Review

Current Issues and Clinical Evidence in Tumor-Infiltrating Lymphocytes in Breast Cancer: Sung Gwe Ahn, Joon Jeong, SoonWon Hong, Woo Hee Jung; J Pathol Transl Med. 2015;49(5):355-363. Published online August 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.29

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With the advance in personalized therapeutic strategies in patients with breast cancer, there is an increasing need for biomarker-guided therapy. Although the immunogenicity of breast cancer has not been strongly considered in research or practice, tumor-infiltrating lymphocytes (TILs) are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value and the potential for predictive value, particularly in triple-negative and human epidermal growth factor receptor 2–positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy. To date, no standardized methodology for measuring TILs has been established. In this article, we review current issues and clinical evidence for the use of TILs in breast cancer.

Citations

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World Journal of Surgery.2023; 47(5): 1238. CrossRef
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Predictors of Neoadjuvant Chemotherapy Response in Breast Cancer: A Review

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Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression
C. Van Berckelaer, C. Rypens, P. van Dam, L. Pouillon, M. Parizel, K. A. Schats, M. Kockx, W. A. A. Tjalma, P. Vermeulen, S. van Laere, F. Bertucci, C. Colpaert, L. Dirix
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Acta Oncologica.2018; 57(1): 74. CrossRef
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Cancer and Metastasis Reviews.2018; 37(2-3): 491. CrossRef
Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers
So Jeong Lee, Cheong-Soo Hwang, Young-Keum Kim, Hyun Jung Lee, Sang-Jeong Ahn, Nari Shin, Jung Hee Lee, Dong Hoon Shin, Kyung Un Choi, Do Youn Park, Chang Hun Lee, Gi Young Huh, Mi Young Sol, Hee Jin Lee, Gyungyub Gong, Jee Yeon Kim, Ahrong Kim
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Glutaminase expression is a poor prognostic factor in node-positive triple-negative breast cancer patients with a high level of tumor-infiltrating lymphocytes
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Tumor Biology.2017; 39(4): 101042831769502. CrossRef
Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer
In Hye Song, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, In Ah Park, Young-Ae Kim, Suk Young Park, Jin Roh, Gyungyub Gong, Hee Jin Lee
Cancer Research and Treatment.2017; 49(2): 399. CrossRef
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Weiwei Zhao, Peng Wang, Huixun Jia, Menglei Chen, Xiaoli Gu, Minghui Liu, Zhe Zhang, Wenwu Cheng, Zhenyu Wu
BMC Cancer.2017;[Epub] CrossRef
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Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Scientific Reports.2017;[Epub] CrossRef
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Kyueng-Whan Min, Dong-Hoon Kim, Sung-Im Do, Seoung Wan Chae, Kyungeun Kim, Jin Hee Sohn, Jung-Soo Pyo, Hyun Joo Lee, Dong Hyun Kim, Sukjoong Oh, Seon Hyeong Choi, Yong Lai Park, Chan Heun Park, Eun-Kyung Kim, Mi Jung Kwon, Jinwon Seo, Kyoung Min Moon
Virchows Archiv.2016; 468(4): 409. CrossRef
Cytoplasmic expression of high mobility group B1 (HMGB1) is associated with tumor‐infiltrating lymphocytes (TILs) in breast cancer
Hee Jin Lee, Ahrong Kim, In Hye Song, In Ah Park, Jong Han Yu, Jin Hee Ahn, Gyungyub Gong
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Journal of Breast Cancer.2016; 19(4): 385. CrossRef

Original Articles

Proposal for Creating a Guideline for Cancer Registration of Microinvasive Tumors of the Breast and Ovary (II): Jin Hee Sohn, Gyungyub Gong, Kyu Rae Kim, Chang Suk Kang, Youn Soo Lee, Jin Man Kim, Woo Hee Jung, Kwang Sun Suh; Korean J Pathol. 2012;46(3):226-232. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.226

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Abstract PDF

Background

Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts.

Methods

As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP.

Results

Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature.

Conclusions

Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

Citations

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Update on the Proposal for Creating a Guideline for Cancer Registration of the Gastrointestinal Tumors (I-2)
Eun Sun Jung, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Won Ae Lee, Hee Eun Lee, Sunhoo Park, Jin Hee Sohn, So-Young Jin
Korean Journal of Pathology.2012; 46(5): 443. CrossRef
A Proposal for Creating a Guideline for Cancer Registration of the Fibromatosis, PEComa Group, Malignant LymphomaIn Situand Dendritic Cell Tumors (III)
Changyoung Yoo, Chang Suk Kang, Yoon La Choi, Hye Yoon Kang, Jin Man Kim, Young Hye Koh, Joo Hee Lee, Seung Sook Lee, In Sun Kim, Dong Hoon Kim, Yong Ku Park, Jin Hee Sohn
Korean Journal of Pathology.2012; 46(5): 436. CrossRef

Fine Needle Aspiration Cytology of Solid and papillary Neoplasm of the Pancreas: Report of a Case.: Mee Yon Cho, Kwang Gil Lee, Kyi Beom Lee, Hyeun Joo Jeong, Woo Hee Jung; Korean J Cytopathol. 1990;1(1):85-92.

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Abstract PDF: We present the cytologic features of a case of solid and papillary neoplasm of the pancreas. Cytologically, the tumor was composed of a monotonous population of polygonal cells containing ecentrically located round nuclei with one or two distinct small nucleoli and a finely stippled chromatin pattern. The tumor cells were similar to those of the islet cell tumor and showed isolated loosety aggregated and solid sheedts or large cell clumps. The large cell clumps revealed a branching papillary structure containing fibrovascular central core, which is characteristic histologic feature of solid and papillary neoplasm of the pancreas. The case was confirmed by tissue examination including histochemical immunohistochemical and electron microscopical studies. Utrastructurally, the tumor cells contanined a few membrane-bound electron dense granules.

Correlation and Accuracy Between Fine Needle Aspiration Cytology of Thyroid Lesions and Histopathologic Diagnosis: Analysis of 322 Histopathologically Confirmed Cases.: Jaseung Koo, Woo Hee Jung, Seokwoo Yang, SoonWon Hong; Korean J Cytopathol. 2008;19(2):144-151.; DOI: https://doi.org/10.3338/kjc.2008.19.2.144

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Abstract PDF

Fine needle aspiration (FNA) cytology is the decisive test in the preoperative diagnostics of thyroid nodules. Here we share our institutional experience about thyroid aspiration and give suggestions for suspicious cytology results. Three hundred twenty-two cases in 270 patients (mean age 47.4 years, 243 women and 27 men) who underwent thyroidectomy were reviewed. Among the 322 cases, the FNA diagnosis of "positive for malignancy" was 87 cases (27.0%), "suggestive of malignancy" 30 cases (9.3%), "suspicious for malignancy" 61 cases (18.9%), "negative for malignancy" 102 cases (31.7%), and "unsatisfactory smear" 42 cases (13.0%). Eighty seven cases (100%) out of "positive for malignancy", 29 cases (96.7%) out of "suggestive of malignancy", and 39 cases (64.0%) out of "suspicious for malignancy" were papillary carcinoma (148 cases, 95.5%), or follicular carcinoma (2 cases, 1.3%), or metastatic carcinoma (1 case, 0.6%). Seventeen patients who had only negative or unsatisfactory cytology underwent thyroidectomy and nine cases (52.9%) were papillary carcinoma. We suggest that: the cytology diagnosis of "suggestive of malignancy" could be regarded as "positive for malignancy", the cytology diagnosis of "suspicious of malignancy" should be carefully correlated with clinico-radiologic manifestation, and even a negative or unsatisfactory smear should be carefully followed up.

Citations

Citations to this article as recorded by

Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy
Changyoung Yoo, Hyun Joo Choi, Soyoung Im, Ji Han Jung, Kiouk Min, Chang Suk Kang, Young-Jin Suh
Korean Journal of Pathology.2013; 47(1): 61. CrossRef

Large Cell Neuroendocrine Carcinoma of the Lung: Report of three cases.: Jai Hyang Go, Sun Ree Jung, Dong Hwan Shin, Woo Hee Jung; Korean J Pathol. 1995;29(4):511-516.

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Abstract PDF: We report three cases of neuroendocrine tumors of the lung characterized by large pleomorphic cell with frequent mitosis, which show neuroendocrine differentiation by both light microscopy or electron microscopy and iminunohistochemistry. These tumors have been categorized as large cell neuroendocrine carcinoma by Travis et al.(1991) in contrast with non-small cell lung cancer with neuroendocrine differentiation. In the latter, neuroendocrine differentiation is not evident by light microscopy and must be demonstrated by imunohistochemstry or by electron microscopy. The prognosis of large cell neuroendocrine carcinoma, together with non-small cell lung cancer with neuroendocrine differentiation, appears to be worse than cancer without neuroendocrine differentiation and intermediate between atypical carcinoid and small cell lung cancer. Larger numbers of patients will be needed to demonstrate significant differences in survival.

The Relation between Cell Proliferation and Apoptosis According to the Histologic Types in Chemically Induced Rat Mammary Tumorigenesis.: Tae Jung Jang, Woo Hee Jung, Kwang Gil Lee; Korean J Pathol. 1998;32(3):174-185.

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Abstract PDF: Balancing the rates of cell proliferation and cell death is important in maintaining normal tissue homeostasis. The relationship among apoptosis, cell proliferation and factors influencing apoptosis according to the histologic types in chemically induced mammary tumorigenesis appears important in understanding the pathogenesis of breast carcinoma. In this study, we investigated alterations in the kinetics of cell proliferation and apoptosis during rat mammary tumorigenesis induced by 7, 12-dimethylbenzanthracene (DMBA) and we related these changes to the expressions of bcl-2, p53, and TGF-beta. Seven-week-old female Sprague-Dawley rats were divided into an experimental group (20 mg/ml DMBA by oral intubation) and a control group. The results were as follows. 1. In the experimental group, breast tumors occurred in twenty two of fifty nine rats(37.3%, 22/59), and the total number of tumors was 100 (4.5 2.0/rat). The histological classification was infiltrating ductal carcinomas (n=5), ductal carcinomas with focal invasion (n=10), intraductal carcinomas (n=36), adenomas accompanied with intraductal proliferation (n=35), intraductal proliferation (n=9), and adenomas (n=5); 2. The differentiation of terminal end bud into alveolar bud (AB) in the experimental group was significantly lower than that of the control group (p<0.05); 3. BrdU labeled tumor cells were mainly located at the peripheral portion of tumor cell nests. BrdU labeling indices were highest in ductal carcinomas, less pronounced in intraductal proliferation, and lowest in adenomas, whereas apoptosis levels were highest in adenomas, less pronounced in intraductal proliferation, and lowest in ductal carcinomas (p<0.05); 4. p53 protein was not expressed in any breast tumors. Although the expression of bcl-2 protein was highest in infiltrating and focal infiltrative ductal carcinomas (58.3%), compared with adenomas, intraductal proliferation, and intraductal carcinomas (p<0.05), the extent of its expression was less than 1% of all tumor cells; 5. TGF-beta was mainly expressed in the central portion of tumor cell nests rather than in peripheral portion, and TGF-beta immunoreactive tumor cells displayed good differentiation and did not reveal BrdU immunoreactivity. TGF-beta labeling index of infiltrating and focal infiltrative ductal carcinomas was significantly higher than that of intraductal carcinomas, intraductal proliferation, and adenomas (p<0.05). Based on these results, it is thought that high cell proliferation and the suppression of apoptosis are closely associated with DMBA-induced rat mammary carcinogenesis. However, the suppression of apoptosis is not related to p53 mutation, bcl-2, and TGF-beta. TGF-beta seems to be reversely related to tumor cell proliferation but closely associated with the progression of the tumor, especially an invasion of breast carcinomas.

Correlation of Heregulin mRNA and Her-2/neu Protein Expression with Node Metastasis and DNA Ploidy Pattern in Human Invasive Breast Carcinoma.: Yee Jeong Kim, Woo Hee Jung, Hyde Lee, Sung Kong Lee, In Gul Moon, Kwang Gil Lee; Korean J Pathol. 1998;32(8):563-573.

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Abstract: The Her-2/neu protooncogene encodes a transmembrane tyrosine kinase that is structurally homologous to the receptor for epidermal growth factor. Its amplification and overexpression are associated with poor prognosis in breast cancer patients. Neu differentiation factor is a ligand for Her-2/neu protooncogene and was detected in ras-transformed rat fibroblasts. Heregulin (human homologue of neu differentiation factor) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation and induces growth arrest or stimulation and differentiation in human breast cancer cell lines. In this study we examined the expression of heregulin mRNA by nested reverse transcription (RT) PCR with fresh tissue, Her-2/neu protein, ICAM-1 and steroid receptors by immunohistochemistry, and DNA ploidy pattern by flow cytometry with paraffin-embedded tissue in invasive breast carcinoma. We compared the data with nodal status, lymphovascular invasion, steroid receptor status and DNA ploidy pattern. For RT-PCR to heregulin mRNA, 38 cases of fresh breast cancer tissue were obtained. Total 68 cases of invasive breast carcinoma tissue were fixed in formalin, which were used for routine histology, immunohistochemistry and flow cytometry. The results are as follows; 1) Heregulin mRNA was expressed in 86.1% of patients with invasive breast carcinoma and 100% of patients with benign breast lesion using nested RT-PCR analysis. 2) Her-2/neu protein was overexpressed in 50.0% of tumors using immunohistochemistry. The expression of Her-2/neu protein was significantly correlated with high counts of lymph nodes with metastasis (p<0.05), and high nuclear grade (p<0.05). 3) Her-2/neu protein overexpression was significantly correlated with a high DNA index(p<0.05). All of the tumors showing Her-2/neu protein overexpression and no heregulin mRNA expression revealed near tetraploid DNA content. However, both Her-2/neu overexpression and heregulin mRNA expressing tumors revealed near tetraploidy in 38.9% and diploidy in 50.0%. Based on these results, heregulin mRNA expression rate was 86.1% in human invasive breast carcinoma. Her-2/neu protein overexpression is associated with high positive lymph node number and DNA index. Statistically significant reverse correlation with lymph node metastasis is not present.

Histopathologic Findings of Mastopathy in Diabetes Mellitus.: Jae Ho Han, Hee Jung Kim, Woo Hee Jung, Ki Keun Oh; Korean J Pathol. 1999;33(7):503-506.

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Abstract PDF: Diabetic mastopathy is a clinicopathologic entity which was first described as a dense fibrous breast mass in insulin-dependent diabetes mellitus. The purpose of this article was to document diabetic mastopathy histologically which had been diagnosed as fibrocystic disease and to avoid unnecessary surgical procedures in breast mass simulating malignancy in diabetic patients. We examined eight excisional breast biopsies from seven patients. Three diabetic patients with type I insulin-dependent diabetes mellitus presented with bilateral (2 patients) or unilateral (1 patient) rapidly growing palpable breast masses. Four patients with type II noninsulin-dependent diabetes mellitus presented with bilateral (2 patients) or unilateral breast mass (1 patient). One patient had no symptoms. All of them had late complications of diabetes mellitus such as nephropathy, neuropathy and retinopathy. Mammographic findings such as ill- defined mass density and asymmetric increased density suggested malignancy. However, all of them had been diagnosed as fibrocystic disease. On review, the most consistent pathologic finding was keloid-like stromal fibrosis. Others were ductitis or ductulitis, thickening of basement membrane of ducts or ductules, mononuclear perivasculitis and lobulitis. Six of eight breast satisfied all five criteria for diabetic mastopathy.

DNA Ploidy Analysis as a Prognostic Indicator in Phyllodes Tumor of the Breast.: Hee Jung Kim, Jae Ho Han, Woo Hee Jung, Hy De Lee; Korean J Pathol. 1999;33(7):507-516.

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Abstract PDF: DNA ploidy analysis using flow cytometry was performed on sixty six cases of phyllodes tumor of the breast including benign, low grade and high grade malignant phyllodes tumor. The rate of aneuploidy was 41.2% in high grade malignant phyllodes tumor and 4.8% in benign phyllodes tumor. No aneuploidy was noted in low grade malignant phyllodes tumor. The recurrence rate according to DNA ploidy pattern revealed 16.7% of aneuploidy and 7.7% of diploidy. In the aneuploid cases, the DNA index of high grade malignant phyllodes tumor was higher than benign phyllodes tumor. Morever, in diploid cases, %SG2M were significantly higher in high grade malignant phyllodes tumor. Therefore, we conclude that DNA ploidy analysis as well as histologic characteristics such as cellularity, pleomorphism of stromal cells and mitoses is useful parameters in the diagnosis, recurrence and prognostic predictors of phyllodes tumor.

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.

Relationship among the Expression of Cyclin D1, p21, and p53 Protein, and Prognosis in Non-Small Cell Lung Carcinomas.: Seok Woo Yang, Sang Ho Cho, Woo Ick Yang, Woo Hee Jung, Chul Min Ahn, Doo Yun Lee; Korean J Pathol. 1999;33(12):1120-1130.

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Abstract PDF: Recently, cell cycle regulators have been suggested as new prognostic factors of the lung cancer. In this study, we evaluated the expression of cyclin D1, p21, and p53 using the X2-test, with regard to the stage of the patients, histologic type, and histologic differentiation in the 135 cases of non-small cell lung carcinomas (NSCLC). To evaluate the confounding effects among cyclin D1, p21, and p53 on X2-test analysis, we used the Mantel-Haenzel test. The NSCLC in this study included 82 cases of squamous cell carcinoma and 53 cases of adenocarcinoma. Each nuclear staining of cyclin D1, p21, and p53 was observed in 65 cases (48.1%), in 54 cases (40.0%), and in 81 cases (60.0%) of NSCLCs, respectively. Only p53 expression was significantly associated with the stage (stage I, II, IIIa) (p<0.05) and squamous cell carcinoma (p<0.05). On the other hand, cyclin D1 expression was significantly associated with the histologic differentiation. The confounding effects among cyclin D1, p21, and p53 revealed that only p21 expression changed the relationship between p53 and stage. In this regard, further study is needed.

Anticancer Effect and Apoptosis of All-trans-retinoic Acid on the Human Ovarian Epithelial Carcinoma Cell Lines.: Jee Young Han, Woo Hee Jung, Tai Seung Kim; Korean J Pathol. 2000;34(3):225-234.

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Abstract PDF: Ovarian carcinoma is a serious disease in women. Some reports revealed all-trans-retinoic acid (tRA) inhibited the proliferation of ovarian carcinoma cell lines and induced apoptosis. The aim of this study was to evaluate the anticancer and apoptotic effects of tRA and the expression of the retinoic acid receptor (RAR) alpha, beta, gamma, p53, bcl-2, and c-myc genes on the ovarian carcinoma cell lines, NIH OVCAR3 and SKOV3. In both cell lines, the proliferation of tumor cells was inhibited and characteristic morphologic patterns of apoptosis were shown after treatment of tRA. The number of apoptotic cells and the percentage of apoptosis were increased after treatment of tRA. The gel electrophoresis revealed the DNA ladder pattern in the NIH OVCAR3. Gene expressions were observed using northern blotting. There was no RARalpha expression in both cell lines. In NIH OVCAR3, there was no changes in the expression of RARbeta and bcl-2 gene. The RARgamma gene expression of tRA treated group was slightly increased, but p53 gene expression was decreased, and c-myc gene was not expressed. In SKOV3, the expressions of RARbeta, gamma, and p53 genes were increased and that of bcl-2 was decreased in the tRA treated group. There was no change in c-myc gene expression. These results suggest tRA has anticancer and apoptotic effect on both ovarian carcinoma cell lines. RARbeta, RARgamma, bcl-2, and p53 gene expressions were correlated with these effects of tRA on SKOV3 but not on NIH OVCAR3.

Expression of Matrix Metalloproteinase and Tissue Inhibitor of Metallproteinase in Breast Carcinoma Related to Angiogenesis and Invasion.: Yoon Jung Choi, Woo Hee Jung, Hy De Lee, Kwang Gil Lee; Korean J Pathol. 2000;34(9):652-664.

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Abstract PDF: Among the enzymes which are responsible for basement membrane breakdown, matrix metalloproteinases (MMP) form a family of neutral proteases that are regulated at the levels of gene transcription, proenzyme activation by the cleavage of protein, and the inhibition of the active enzyme by tissue inhibitors of matrix metalloproteinases (TIMP). Recent reports have demonstrated that the expression of these proteolytic enzymes are elevated in several solid tumors and that it can be associated with invasiveness and poor prognosis. We examined the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemistry in 160 cases of infiltrating ductal carcinoma. And we compared these data with the established prognostic parameters - tumor size, nodal status, clinical stage, hormonal receptor status, microvessel density, and TGF-beta1 expression in order to evaluate how MMP and TIMP expression are associated with breast cancer progression and prognosis. Microvessel density in invasive breast carcinoma was significantly correlated with tumor size and recurrence (p<0.05). The immunohistochemical expression of TGF-beta1 was significantly associated with tumor size, lymph node metastasis, and clinical stage (p<0.05). The microvessel density was significantly correlated with TGF-beta1 expression in more than 50% of tumor cells. The immunohistochemical expression of MMP-2 and MMP-9 were significantly correlated with nodal metastasis and absence of immunoreactivity for estrogen and progesterone receptors. The immunohistochemical expression of TIMP-1 was inversely correlated with clinical stage and microvessel density while that of TIMP-2 was inversely correlated with clinical stage (p<0.05). Small size of tumor, presence of progesterone receptor, highly differentiated histologic grade, and absence of immunoreactivity for MMP-9 were significantly associated with higher survival rate, but in multivariate analysis only tumor size and MMP-9 expression appeared to affect survival independently.

Relationship between Epstein-Barr Virus (EBV), Apoptosis and Lymphocytic Infiltration in Gastric Carcinoma with Lymphoid Rich Stroma.: Tae Heon Kim, Mee Yon Cho, Sang Yeop Yi, Woo Hee Jung, Kwang Hwa Park; Korean J Pathol. 2001;35(5):368-375.

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Abstract PDF: BACKGROUND
Gastric carcinoma with lymphoid rich stroma (GCLRS) is an undifferentiated gastric carcinoma with heavy lymphocytic infiltrate. In order to clarify the relationship between lymphocytic infiltration and apoptosis in gastric carcinoma, we investigated the association of apoptosis with apoptotic proteins and Epstein-Barr Virus (EBV) expression in GCLRS.
METHODS
We performed immunohistochemical stains for bcl-2, bax and in situ hybridization for EBER (Epstein-Barr virus encoded RNA)-1 and the terminal deoxynucleaotidil transferase mediated dUTP-digoxigenin nick end labelling (TUNEL) technique using 47 out of 1635 gastric carcinoma cases.
RESULTS
The prevalence of GCLRS was 1.47% (24/1635). The prevalence of EBV involvement in GCLRS (79%, 19/24) was significantly higher than that of gastric carcinoma with lymphoid poor stroma (GCLPS) (8.7%, 2/23). The immunohistochemical stain for bcl-2 revealed negative expressions in all cases, but that of bax was positive for in all cases. bax was significantly correlated with the apototic index (P<0.05). There was no statistical significance between lymphocytic infiltration and apoptosis. The lymphocytic infiltration significantly correlated with the expression of EBV (P<0.05) but not with survival rate and apoptosis. However, most of the GCLRS displayed low clinical stages(stage IA, B), and we suggest that was a proper reason for a good prognosis.
CONCLUSIONS
These results support that EBV is associated with GCLRS, and there is no relationship between apoptosis and bcl-2, bax and prognosis. They also suggest that EBV infection play an important role in the gastric carcinogenesis.

Cytologic findings of pancreatic islet cell tumor with lymph node metastasis.: Yee Jeong Kim, Yoon Jung Choi, Kyu Rae Kim, Woo Hee Jung, Kwang Gil Lee; Korean J Cytopathol. 1992;3(2):60-66.

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Abstract PDF: No abstract available.

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