Journal of Pathology and Translational Medicine

Original Articles

Extramural Perineural Invasion in pT3 and pT4 Gastric Carcinomas: Alejandro España-Ferrufino, Leonardo S. Lino-Silva, Rosa A. Salcedo-Hernández; J Pathol Transl Med. 2018;52(2):79-84. Published online November 9, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.01

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Background
Perineural invasion (PNI) is widely studied in malignant tumors, and its prognostic significance is well demonstrated. Most studies have focused on evaluating the mural PNI (mPNI); however, extramural PNI (ePNI) may influence the prognosis in gastric cancer. We evaluated the prognostic value of ePNI compared with mPNI in gastric cancer in this observational comparative cross-sectional study.
Methods
Seventy-three pT3 and pT4 gastric carcinomas with PNI were evaluated. Forty-eight (65.7%) were in the mPNI group and the remaining in the ePNI group.
Results
Clinicopathologic characteristics between the two groups were similar, except for the outcomes. The 5-year disease-specific survival (DSS) rate was 64% for the mPNI group and 50% for the ePNI group (p=.039), a difference that did not remain significant in multivariate analysis. The only independent adverse prognostic factor in multivariate analysis was the presence of lymph node metastasis (hazard ratio, 1.757; 95% confidence interval, 1.082 to 2.854; p=.023).
Conclusions
We demonstrated the prognostic effect of ePNI for DSS in surgically resected pT3–pT4 gastric cancer patients. ePNI could be considered in the staging and prognostic systems of gastric cancer to stratify patients with a high risk of recurrence.

Citations

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Investigation of Conditioned Media-Mediated Communication between Pancreatic Cancer Cells and Neurons
Didem Karakaş
Acta Medica Nicomedia.2025; 8(1): 15. CrossRef
Innervating 3D in vitro models: bioengineering and design blueprints
Mariana-Tomás de Carvalho, Margarida Henriques-Pereira, Maria V. Monteiro, Meriem Lamghari, João F. Mano, Vítor M. Gaspar
Trends in Biotechnology.2025; 43(11): 2743. CrossRef
Development and validation of a preoperative CT-based risk score integrating morphological and body composition parameters to predict recurrence-free survival in gastric cancer patients following curative surgery
Ruochen Cong, Jialei Ming, Ruonan Xu, Liyu Zhu, Xinyue Wang, Zhengqi Zhu
European Journal of Radiology.2025; 191: 112318. CrossRef
Comparison of 2D and 3D measured iodine concentration of gastric adenocarcinoma on spectral-CT and their relationship with perineural invasion
Tianxia Bei, Xiaoqiang Yao, Xuejun Chen, Yue Wu, Jing Li, Jinrong Qu
BMC Medical Imaging.2025;[Epub] CrossRef
Neural control of tumor immunity
Burak Kizil, Francesco De Virgiliis, Christoph Scheiermann
The FEBS Journal.2024; 291(21): 4670. CrossRef
Spectral CT-based nomogram for preoperative prediction of perineural invasion in locally advanced gastric cancer: a prospective study
Jing Li, Shuning Xu, Yi Wang, Mengjie Fang, Fei Ma, Chunmiao Xu, Hailiang Li
European Radiology.2023; 33(7): 5172. CrossRef
Crosstalk between cancer cells and the nervous system
Meng Huang, Gu Gong, Yicheng Deng, Xinmiao Long, Wenyong Long, Qing Liu, Wei Zhao, Rufu Chen
Medicine Advances.2023; 1(3): 173. CrossRef
Targeting tumor innervation: premises, promises, and challenges
Xinyu Li, Xueqiang Peng, Shuo Yang, Shibo Wei, Qing Fan, Jingang Liu, Liang Yang, Hangyu Li
Cell Death Discovery.2022;[Epub] CrossRef
Cancer-Associated Neurogenesis and Nerve-Cancer Cross-talk
Deborah A. Silverman, Vena K. Martinez, Patrick M. Dougherty, Jeffrey N. Myers, George A. Calin, Moran Amit
Cancer Research.2021; 81(6): 1431. CrossRef
Perineural Invasion and Postoperative Adjuvant Chemotherapy Efficacy in Patients With Gastric Cancer
Qing Tao, Wen Zhu, Xiaohui Zhao, Mei Li, Yongqian Shu, Deqiang Wang, Xiaoqin Li
Frontiers in Oncology.2020;[Epub] CrossRef
Perineural invasion as a predictive factor for survival outcome in gastric cancer patients: a systematic review and meta-analysis
Bochao Zhao, Wu Lv, Di Mei, Rui Luo, Shiyang Bao, Baojun Huang, Jie Lin
Journal of Clinical Pathology.2020; 73(9): 544. CrossRef
Consensus-Expressed CXCL8 and MMP9 Identified by Meta-Analyzed Perineural Invasion Gene Signature in Gastric Cancer Microarray Data
Xiuzhi Jia, Minjia Lu, Chen Rui, Ying Xiao
Frontiers in Genetics.2019;[Epub] CrossRef

HDAC1 Expression in Invasive Ductal Carcinoma of the Breast and Its Value as a Good Prognostic Factor: Minseob Eom, Sung Soo Oh, Sayamaa Lkhagvadorj, Airi Han, Kwang Hwa Park; Korean J Pathol. 2012;46(4):311-317. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.311

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Abstract PDF

Background

Histone deacetylase 1 (HDAC1) is associated with the expression and function of estrogen receptors and the proliferation of tumor cells, and has been considered a very important factor in breast tumor progression and prognosis. Several studies have reported an association between HDAC1 expression and poorer prognosis in cancers including breast cancer, with a few exceptions. However, because of the dearth of studies on HDAC1 expression in breast cancer, its significance for breast cancer prognosis has not been well defined. Therefore, we examined HDAC1 expression in invasive ductal carcinoma (IDC), the most common breast cancer, and investigated its potential prognostic significance.

Methods

We used 203 IDC tissue samples. Immunohistochemical stains for HDAC1 and real-time polymerase chain reaction for HDAC1 mRNA were performed and the results were compared to generally well-established prognostic factors in breast cancer and patient survival rates.

Results

HDAC1 expression was significantly reduced in proportion to higher histologic grade, higher nuclear pleomorphism score, and higher mitotic counts, and with lower estrogen receptor expression. Furthermore, it was significantly associated with the survival rate.

Conclusions

HDAC1 expression is a good prognostic indicator in IDC.

Citations

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Are HDAC and Glutamine Synthetase Expression Levels Associated with Ga68-DOTATATE PET/CT Data and Prognosis in Gastroenteropancreatic Neuroendocrine Tumours?
Ozge Ulas, Ramazan Oguz Yuceer, Zekiye Hasbek, Hatice Ozer, Kerim Seker, Mukaddes Yılmaz, Mahmut Uçar
Medicina.2025; 61(11): 1952. CrossRef
SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46‐mediated HDAC1 degradation
Zihan Zhang, Xiaoping Liu, Lei Li, Yang Yang, Jianguo Yang, Yue Wang, Jiajing Wu, Xiaodi Wu, Lin Shan, Fei Pei, Jianying Liu, Shu Wang, Wei Li, Luyang Sun, Jing Liang, Yongfeng Shang
The EMBO Journal.2021;[Epub] CrossRef
The Impact of Androgen Receptor and Histone Deacetylase 1 Expression on the Prognosis of Ductal Carcinoma In Situ
Choong Man Lee, Il Yong Chung, Yangsoon Park, Keong Won Yun, Hwi Gyeong Jo, Hye Jin Park, Hee Jin Lee, Sae Byul Lee, Hee Jeong Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn, Jisun Kim
Journal of Breast Cancer.2020; 23(6): 610. CrossRef
Prognostic and clinical significance of histone deacetylase 1 expression in breast cancer: A meta-analysis
Weiqiang Qiao, Heyang Liu, Ruidong Liu, Qipeng Liu, Ting Zhang, Wanying Guo, Peng Li, Miao Deng
Clinica Chimica Acta.2018; 483: 209. CrossRef
HDAC1 triggers the proliferation and migration of breast cancer cells via upregulation of interleukin-8
Zhaohui Tang, Sijuan Ding, Honglin Huang, Pengfei Luo, Bohua Qing, Siyuan Zhang, Ruoting Tang
Biological Chemistry.2017; 398(12): 1347. CrossRef
Identification of novel histone deacetylase 1 inhibitors by combined pharmacophore modeling, 3D-QSAR analysis, in silico screening and Density Functional Theory (DFT) approaches
Sanjay K. Choubey, Richard Mariadasse, Santhosh Rajendran, Jeyakanthan Jeyaraman
Journal of Molecular Structure.2016; 1125: 391. CrossRef
The Potential of Histone Deacetylase Inhibitors in Breast Cancer Therapy
Namita Chatterjee, Martin Tenniswood
Breast Cancer Management.2015; 4(2): 85. CrossRef

Prognostic Implication of Programmed Death-1-Positive Tumor-infiltrating Lymphocytes in Diffuse Large B-Cell Lymphoma.: Young Sin Ko, Young Ha Oh, Chan Kum Park, Wook Youn Kim, Hye Seung Han, So Dug Lim, Tae Sook Hwang, Wan Seop Kim; Korean J Pathol. 2011;45(6):573-581.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.573

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Abstract PDF

BACKGROUND
Programmed death-1 (PD-1) is physiologically expressed by germinal center-associated helper T-cells and has an inhibitory effect on T-cell activity.
METHODS
We examined 63 cases of diffuse large B-cell lymphoma (DLBCL) and determined the number of PD-1-positive helper T-cells in a representative tumor area after immunohistochemical staining using a monoclonal antibody against PD-1. The PD-1-positive cells were counted in 3 high-power fields (HPFs; 400x).
RESULTS
Patients were divided into 2 groups: one with a high number of PD-1-positive cells (>20/HPF, n=33) and one with a low number of PD-1-positive cells (< or =20/HPF, n=30). The former group showed decreased overall survival, but at a statistically non-significant level (p=0.073). A high number of PD-1-positive cells was more common in patients at an advanced clinical stage and with high international prognostic index score (p=0.025 and p=0.026, respectively). The number of extranodal sites also somewhat correlated with the PD-1 staining status (p=0.071). However, the number of PD-1-positive cells was not associated with patient age, serum lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance score.
CONCLUSIONS
The high number of PD-1-positive cells might be associated with an unfavorable outcome in DLBCL patients.

Citations

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Mechanisms of PD-1/PD-L1 expression and prognostic relevance in non-Hodgkin lymphoma: a summary of immunohistochemical studies
Pauline Gravelle, Barbara Burroni, Sarah Péricart, Cédric Rossi, Christine Bezombes, Marie Tosolini, Diane Damotte, Pierre Brousset, Jean-Jacques Fournié, Camille Laurent
Oncotarget.2017; 8(27): 44960. CrossRef
Expression of programmed cell death ligand 1 (PD-L1) in advanced stage EBV-associated extranodal NK/T cell lymphoma is associated with better prognosis
Wook Youn Kim, Ho Young Jung, Soo Jeong Nam, Tae Min Kim, Dae Seog Heo, Chul-Woo Kim, Yoon Kyung Jeon
Virchows Archiv.2016; 469(5): 581. CrossRef

Histologic Parameters Predicting Survival of Patients with Multiple Non-small Cell Lung Cancers.: Joo Young Kim, Hee Jin Lee, Jun Kang, Se Jin Jang; Korean J Pathol. 2011;45(5):506-515.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.506

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Abstract PDF: BACKGROUND
In multiple lung cancers (MLCs), distinction between intrapulmonary metastases and multiple primary tumors is important for staging and prognosis. In this study, we have investigated histopathologic prognostic factors of patients with MLCs.
METHODS
Histologic subtype, size differences, lobar location, lymphovascular invasion (LVI), size of the largest tumor, nodal status, number of tumors, morphology of tumor periphery, and immunohistochemical profiles using eight antibodies, were analyzed in 65 patients with MLCs.
RESULTS
There was no significant difference in the survivals of patients with multiple primary tumors and intrapulmonary metastases, as determined by the Martini-Melamed criteria (p=0.654). Risk grouping by four histologic parameters, LVI, margin morphology, size differences, and lobar locations of paired tumors were prognostic. The patients with one or two of aforementioned parameters had significantly longer survival than those with three or four parameters (p=0.017). In patients with largest mass (< or =5 cm), the risk grouping was found to be an independent prognostic factor (p=0.022). However, differences in immunohistochemical staining were not related to patients' survival.
CONCLUSIONS
A risk grouping of MLC patients by using combinations of histologic parameters can be a useful tool in evaluating the survival of patients with MLCs, and may indicate clonal relationship between multiple tumors.

The Stromal Overexpression of Decay Accelerating Factor (DAF/CD55) Correlates with Poor Clinical Outcome in Colorectal Cancer Patients.: Tae Hwa Baek, Joo Heon Kim, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Hyun Ki Soon, Chang Nam Kim, Che Myong Ko, Dong Wook Kang; Korean J Pathol. 2011;45(5):445-454.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.445

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Abstract PDF

BACKGROUND
Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs).
METHODS
Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated.
RESULTS
CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05). CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis.
CONCLUSIONS
Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.

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Non-canonical extracellular complement pathways and the complosome paradigm in cancer: a scoping review
Camila de Freitas Oliveira-Tore, Amarilis Giaretta de Moraes, Helena Musetti B. S. Plácido, Nathalia M. D. L. Signorini, Pamela Dias Fontana, Tatiane da Piedade Batista Godoy, Angelica Beate Winter Boldt, Iara de Messias
Frontiers in Immunology.2025;[Epub] CrossRef

p53 Protein Expression in Infiltrating Ductal Carcinoma of the Breast.: Soon Hee Jung, Mee Yon Cho, Soo Yong Kim; Korean J Pathol. 1996;30(1):7-14.

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Abstract PDF: Overexpression of the nuclear phosphoprotein p53 is the most common genetic anomaly found in primary human cancer and mutation of the tumor suppressor gene p53 has been identified in breast cancer cell lines. In this study, we evaluated the prognostic significance of p53 protein expression in patients with mammary infiltrating ductal carcinoma and its correlation with histopathologic grade, lymph node status, tumor size, p53 protein expression and survival. Among 53 cases, p53 protein expression was detected in 26(49.1%) cases by immunohistochemistry. There was no correlation between p53 protein overexpression and histopathologic grade(p=0.09) or lymph node status(p=0.38) and between survival and histopathologic grade (p=0.68) or lymph node status(p=0.52). However, p53 protein expression was significantly correlated with survival(p=0.01) and patients with p53 protein-positive tumors showed poorer survival times. But Cox multivariate analysis showed the lymph node status is significant(p=0.01). The authors conclude that the presence of mutant p53 protein and lymph node status may serve a prognostic role, in a subset of mammary infiltrating ductal carcinoma cases.

Immunohistochemical Study of p53 and nm23-H1 Protein in Gastric Carcinoma.: Duck Hwan Kim, Yoen Ju Kim, Seon Eun Yang, Sung Suk Paeng, Hee Jin Chang, Jung Il Suh, Hyo Sook Park; Korean J Pathol. 1996;30(7):587-594.

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Abstract PDF: The p53 gene, which resides on the short arm of chromosome 17, has been described as a tumor suppressor gene playing a role of G1 checkpoint monitering DNA damage, but mutation of this gene has been shown in numerous types of human cancers. The nm23-H1 gene encodes human NDP(nucleotide diphosphate) kinase. The expression of nm23-H1 gene was postulated to inversely correlate with metastatic potential of malignant tumors. We examined immunohistochemical expression in 30 cases of stomach cancers including 10 cases each of early gastric cancers(EGC), advanced gastric cancers without lymph node involvement, and advanced gastric cancers with lymph node involvement, which were stained with mouse monoclonal antibody of p53(PB53-12) and nm23-H1. Positive nuclear staining of p53 was frequently found in advanced gastric cancers with lymph node involvement (80%). The lymph node positive group showed high expression of p53(80%), and low expression of nm23-Hl(30%) than lymph node negative group. There was no significant correlation of p53 and nm23-H1 expression with tumor size, invasion depth, TNM stages, distant metastasis and histologic differentiation. Based on the present study, the expression of p53 and down regulation of nm23-H1 are thought to be correlated with tumor progression and lymph node involvement, and may be a useful prognostic factor in gastric cancers.

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.

Correlation between Tumor Angiogenesis (Microvessel Density), Metastasis and Tumor Cell Proliferation in Colorectal Carcinomas.: Young Chae Chu, Joon Mee Kim; Korean J Pathol. 1997;31(6):517-526.

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Abstract PDF: Tumor angiogenesis has been shown to be associated with metastatic potentials in breast, lung and prostatic carcinomas. The relation between tumor angiogenesis and metastatic potentials in colorectal cancer has not been established to date. We analysed 66 selected patients with colorectal carcinomas (37 with and 29 without nodal metastases) for the microvessel density, tumor proliferation activity, and the clinicopathologic parameters including size, stage, histologic grade, growth pattern, presence of angioinvasion, perineural invasion and lymph node metastasis. For evaluation of microvessel density and tumor proliferative activity, the primary tumors were immunohistochemically stained for CD31 and PCNA. The mean microvessel counts (MVC) per 200X field were 99.27+/-23.28 and 131.35+/-31.48 in node-negative and node-positive patients, respectively. The PCNA index was 39.41+/-5.63% and 56.60+/-7.09% in node-negative and node-positive patients, respectively. MVC and PCNA index were higher in tumors with nodal metastasis (p=0.002, p<0.001), and also correlated each other (sr=0.33, p=0.007). Higher microvessel counts were seen in tumors with advanced stage (p=0.016). Tumor proliferation activity assessed by PCNA immunostaining was significantly higher in tumors with advanced stage, perineural invasion, angioinvasion, poor differentiation and larger size. From these results, MVC and PCNA index in colorectal carcinomas are assumed to be valuable prognostic parameters. Thus assessment of tumor angiogenesis and tumor cell proliferation in colorectal carcinomas may be helpful for the patients in need of aggressive therapy.

Flow Cytometric DNA Analysis of Gastrointestinal Stromal Tumors .: Mee Yon Cho, Soon Won Hong, Soon Hee Jung, Hogeun Kim, Chanil Park; Korean J Pathol. 1997;31(7):608-616.

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Abstract PDF: To evaluate the correlation between the histologic grade and DNA ploidy or proliferation index/S phase fraction (SPF) of gastrointestinal stromal tumors, we performed the DNA analysis using the flow cytometry. Paraffin embedded tissue samples of 57 gastrointestinal stromal tumors were used. The sites of the tumors were: stomach (28), small intestine (23), and large intestine(6). DNA index, proliferative index, and SPF by the flow cytomery were compared with histologic grade. The histologic grade of the gastric tumors were benign (12), borderline (10), and malignant (6). Those of the small intestinal timors were benign (2), borderline (13), and malignant(8). The large intestine were borderline (2), and malignant (4). In stomach, aneuploidy was found in 25.0% of benign, 40.0% of borderline, and 100% of malignant. And there was statistically significant correlation between the histologic grade and ploidy (p < 0.05). By contrast, small and large intestinal tumors showed more frequent aneuploidy in benign than in malignant. The proliferative index was correlated with the histologic grade in gastric tumors (p<0.05), but the SPF was not. In conclusion, the ploidy and proliferative index of gastric tumors are closely correlated to the histologic grade. However, aneuploidy in tumors of the small and large intestine were difficult to predict the malignancy.

Immunohistochemical Study of p53 and E-cadherin Proteins in Prostate Carcinoma.: Lee So Maeng, Won Il Kim, Kyo Young Lee, Young Shin Kim, Chang Suk Kang, Sang In Shim; Korean J Pathol. 1998;32(3):215-221.

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Abstract PDF: Considerable controversy exists concerning the value of histomorphological data in the assessment of the malignant potential of prostate carcinomas. Mutations in the p53 gene resulting in the accumulation of altered p53 proteins with prolonged half-life have been found in a large variety of human malignancies. E-Cadherin is a specific epithelial cell-to- cell adhesion molecule which has previously been found to be expressed in well-differentiated non-invasive carcinoma cell lines, but it is lost in many poorly differentiated invasive cell lines. We performed immunohistochemical staining of p53 and E-cadherin in formalin fixed paraffin embedded tissues of 58 primary prostatic carcinomas. The expression rates of p53 and E-cadherin proteins in prostate carcinoma were positive in 15.5% and 44.8% of the cases, respectively. Histologically high-grade prostate carcinoma shows an increased expression of the p53 protein and a decreased one of the E-cadherin protein (P<0.05). The expression rates of the E-cadherin protein in prostate carcinoma decreased significantly according to the higher clinical stages and PSA levels (P<0.05). There was no accordance between the expression rate of p53 and E-cadherin. There were no significant correlation between each of the clinical stages and the expression rate of p53 protein or the PSA levels and the expression rates of p53 protein (P<0.05). Based on the present study, the expression of p53 and down regulation of E-cadherin are correlated with tumor progression and metastasis, and may be a useful prognostic factor in prostate carcinoma.

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.

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).

Correlation of Expression of CD44, p53 and bcl-2 Protein, DNA Ploidy Pattern, and Clinicopathologic Prognostic Factors in Invasive Ductal Carcinoma of the Breast.: Mi Ja Lee, Ho Jong Jeon, Kweon Cheon Kim; Korean J Pathol. 1999;33(12):1152-1162.

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Abstract PDF: In this study of 64 cases of breast cancer with a clinical follow-up period of more than 5 years, several prognostic factors were evaluated. The purpose of this study was to determine whether any one parameter or group of parameters serves as adequate predictors of tumor behavior and patient's prognosis. Several prognostic factors included clinicopathological variables (patient's age, histologic grade, status of lymph node (LN) metastasis, and tumor size), expression of estrogen receptor (ER), progesterone receptor (PR), p53, bcl-2 and CD44 by immunohistochemistry, and DNA ploidy pattern. The results showed that the expression of ER and PR had a significant inverse correlation with the histologic grade (ER, p=0.05; PR, p<0.05). The expression of p53 protein showed a significant relationship with high histologic grade of tumor (p<0.05). The expression of bcl-2 protein was preferably seen in low histologic grade of tumor (p<0.05) and significantly associated with ER positive or PR positive tumors (ER, p<0.05; PR, p<0.05). This results suggest that bcl-2 protein might play significant roles in ER and PR. The CD44 expression showed a significant relationship with tumor size (p<0.05). The large size and aneuploidy pattern of tumor had a tendency to be associated with shorter patient survival. Cox's multivariate analysis showed that overall survival was affected by LN metastasis because of the shorter survival in patients with LN metastasis. In conclusion, tumor size, DNA ploidy pattern, and LN metastasis were themselves significant predictors of breast cancer survival rate.

Expression of CD44 Splicing Variants v4/5 and v6 in Gastric Adenocarcinoma and Its Relationship with Prognostic Factors.: Lee So Maeng, Hae Kyung Lee, Byung Kee Kim, Eun Jung Lee; Korean J Pathol. 2000;34(2):119-124.

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Abstract PDF: CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and may be a determinant of metastatic and invasive behavior in carcinomas. This study was performed to investigate the relationship between CD44 splicing variants v4/5 and v6 expression and histopathologic prognostic factors (depth of tumor invasion, histologic classification, vascular and lymphatic invasion, and lymph node metastasis) in 107 gastric adenocarcinomas. In 107 cases of gastric carcinoma, the immunohistochemical stainining for CD44 v4/5 and CD44 v6 gave the following results. CD44 v4/5 was expressed in 40.2% and CD44 v6 in 67.3% of gastric carcinomas. The expression of CD44 v4/5 was correlated with histologic classification by Lauren (p<0.05), lymphatic invasion (p<0.05), and lymph node metastasis (p<0.004). In contrast, expression of CD44 v6 had no impact on prognostic markers. This study suggests the role of CD44 v4/5 in invasion, metastasis, and its prognostic significance in gastric adenocarcinoma.

Expression of E-cadherin, Matrix Metalloproteinase, and Vascular Endothelial Growth Factor in Squamous Cell Carcinoma and Adenocarcinoma of the Lung.: Ji Sun Song, Mee Yon Cho, Kwang Hwa Park, Soon Hee Jung, Kwang Gil Lee; Korean J Pathol. 2000;34(12):972-981.

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Abstract PDF: E-cadherin is a calcium-dependent epithelial adhesion molecule which plays a role in the initial step of invasion of cancer cells. The step that follows the migration of separated tumor cells is a proteolytic lysis of basement membrane and extracellular matrix by protease of epithelial and endothelial cells such as matrix metalloproteinase (MMP). Vascular endothelial growth factor (VEGF) is known to be an endothelial cell-specific powerful mitogen as well as a vascular permeability factor. This study is aimed to evaluate the correlation between expression of these factors and pathologic or clinical variables and the roles and prognostic significance of those factors in squmous cell carcinoma and adenocarcinoma of the lung. Immunohistochemical stains were performed for E-cadherin, MMP-2, and VEGF in surgically resected specimens from 90 patients with squmous cell carcinoma and adenocarcinoma of the lung. Mean age of the patients was 59.7 years. Histologic type was categorized into 56 cases of squamous cell carcinoma and 34 cases of adenocarcinoma. Mean survival period of the 35 patients was 54 months. The immunohistochemical stains for E-cadherin, MMP-2, and VEGF revealed positive reaction in 67 cases (74.4%), 43 cases (47.8%), and 34 cases (37.8%), respectively. The expression of E-cadherin was higher in adenocarcinoma (82.4%) than in squamous cell carcinoma (69.6%). MMP-2 was expressed in the tumor cells, especially those invading into the surrounding stroma. The expression of MMP-2 was significantly correlated with the survival rate (p<0.05). The expression of VEGF in the tumor cells was significantly higher in cases with lymph node metastasis (p<0.05). In conclusion, these findings suggest that the expression of MMP-2 and VEGF predict poor prognosis of patients with squmous cell carcinoma and adenocarcinoma of the lung and that VEGF may play a role in tumor metastasis.

Cytologic Findings of Breast Carcinoma in Fine Needle Aspiration: Comparison with Histologic Findings, Stage and Lymph Node Metastasis.: Hee Jin Chang, Duck Hwan Kim, Sung Sook Paeng, Sung Eun Yang, Jin Hee Sohn, Jung Il Suh, Hyo Sook Park; J Pathol Transl Med. 1995;6(1):18-26.

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Abstract PDF: In order compare cytologic findings of breast carcinoma in fine needle aspiration cytology (FANC) with histologic findings and prognostic factors including histologic grading, lymph node metastasis and stage, 79 cases of infiltrating ductal carcinoma diagnosed by FANC and confirmed by histology were analysed. We especially attempted to correlate nuclear grade, cellularity and smear pattern with histologic grade, type, status of lymph node metastasis and stage. The results are as follwos : 2. Individual cell pattern was more frequently identified in high histologic grade and scirrhous or solid-tubular type than in low histolgic grade and papillotubular type. 3. Cellularity increased with higher histologic grade and lymph node metastsis. However cellularity was low in scirrhous type. 4. There is no relationship between nuclear grade and histologic type, between smear pattern and lymph node metastasis or stage, and between cellularity and stage. These results suggest that cytologic findings of breast carcinoma such as nuclear grade, cellularity and smear pattern are indicative of histologic findings in relation to histolgic grade and type. Especially, nuclear grade of FANC may yield valuable prognostic information.

The Study of Proliferating Cell Nuclear Antigen in Colorectal Carcinoma.: Ho Soo Choi, Bok Soog Yang, Ji Shin Lee, Min Cheol Lee; Korean J Pathol. 1995;29(3):311-320.

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Abstract PDF: The determination of proliferative activity in the colorectal mucosa has been used for different purposes as the estimation of cancer risk and the assessment of disease activity in ulcerative colitis. But the prognostic significance of proliferative activity in colorectal carcinomas remains controversial. To investigate the prognostic significance of proliferative activity in colorectal carcinomas, the author estimated the proliferative activity immunohisto chemically using the monoclonal antibody PCNA and compared with clinicopathological data in 62 colorectal carcinomas. The results were as follows: 1) The reactivity of PCNA was more pronounced at the infiltrative margins of the tumors and tumor cells within the vascular or lymphatic channels. 2) The mean PCNA index of colorectal carcinomas was 40.5?0.4%. PCNA indices had positive correlations with lymph node invasion(p<0.05), liver, metastasis(p<0.05), Dukes' stage(p<0.01) and TNM classification(p<0.01), and didn't correlated with location of tumor, size of tumor, histological type and lymphtic or vascular invasion. 3) The patients with high PCNA index(more than 45%) represented higher recurrence or metastasis rate(37.5%) than those with low PCNA index (less than 45%)(19.3%) in Dukes B or C colorectal carcinomas during the follow-up periods, but not significant statistically. These results suggested that the reactivity of PCNA may be a useful prognostic factors in colorectal carcinomas.

Relationship between Immunohistochemical Expression of Cathepsin D and Other Prognostic Factors of Breast Carcinoma.: Kwang Hwa Park, Byeng Woo Park, Kyong Sik Lee, Kwang Gil Lee; Korean J Pathol. 1994;28(6):612-619.

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Abstract PDF: The cathepsin D is a lysosomal protease secreted in excess by breast cancer cells. The function of this enzyme is degradation of the extracellular matrix and proteoglycan. It is induced by estrogens in estrogen receptor positive breast cancer cell lines. On the basis of this, cathepsin D expression in breast cancer cells seems to be correlated with the prognosis. But there is debates in its prognostic significance. Relationship between cathepsin D expression and other prognostic factors of breast cancer was studied. We investigated 51 cases of invasive ductal cell carcinoma of breast removed by open biopsy or mastectomy. All cases were fixed in formalin and embedded in paraffin. We used 46-KD intermediate form of the enzyme for cathepsin D expression on immunohistochemical stain. We observed no significant correlation with age, stage, histologic grade, lymphatic invasion, and estrogen receptor status. Cathepsin D may be an independent factor which is not related with other prognostic factors, especially estrogen receptor status.

Correlation between Expression of c-erbB-2 Oncogene and Various Prognostic Factors in the Colorectal Carcinoma.: Wan Kim, Hong Ran Choi, Ji Shin Lee, Jong Tae Park, Chang Soo Park, Kyu Hyuk Cho; Korean J Pathol. 1993;27(3):217-225.

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Abstract PDF: The c-erbB-2 oncogene, which is a new human proto-oncogene similar to EGFR structurally, generates a glycoprotein of tyrosine kinase family with a molecular weight of 185,000 To evaluate the prognostic significance of c-erbB-2 oncogene expression in colorectal carcinoma, We analysed 73 colorectal carcinomas in paraffin sections immunohistochemically, using the monoclonal antibody specific for the c-erbB-2 oncogene product and correlated with clinicopathological data. The results were as follows 1) The immunoreactivity for c-erbB-2 oncogene was localized to cell membrane of the tumor cells and occasionally observed within the cytoplasm. 2) The positivity of c-erbB-2 oncogene expression was 71.2%(52/73) of the colorectal carcinomas overall. According to the histological types, the positivity of c-erbB-2 oncogene in adenocarcinoma(77.4%) was higher than that in mucinous carcinoma(36.4%)(p<0.05). 3) Expression of c-erbB-2 oncogene was significantly correlated with lymph node metastasis or distant metastasis(p=0.0117), Dukes stage(p=0.0432), and TNM classification(p=0.0102). These results suggest that c-erbB-2 oncogene expression may be used as a prognostic factor of colorectal carcinoma because of its correlation with other clinicopathological prognostic factors.

Pathological Predictor for Prognosis in Gastrointestinal Mesenchymal Neoplasms.: Mee Yon Cho, Ho Guen Kim, Chan Il Park, Yoo Bock Lee; Korean J Pathol. 1991;25(6):528-538.

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Abstract PDF: To evaluate the prognostic predictor and clinicopathologic characteristics of the gastrointestinal (GI) mesenchymal neoplasm, we examined 75 cases of GI mesenchymal tumors surgically resected during 8 years from 1983 to 1990. Various histological parameters referrable to the prognosis, including the Ag-NORs count, were analysed. Fifty cases were followed-up for 1 to 7 years. Sixteen out of these fifty cases died during this period. The location of tumor was the stomach in 33 cases, the small intestine in 31 cases and the large intestine in 11 cases, and the tumor size was variable from 2 to 35 cm in diameter. The GI mesenchymal neoplasm appeared as an extraluminal mass in 50 cases, an intramural mass in 17 cases, and an intraluminal mass in 8 cases. Each tumor was composed of spindle or epithelioid cells, the former cell type being more common than the latter (45 vs 30 cases). Mitotic count of the tumor showed the best correlationship with the survival of patients(p<0.05), although the tumor size and necrosis appeared to have some values. The Ag-NORs count was variable and was not significantly correlated with the patient's prognosis(p>0.05). These results indicate that the mitotic count is the most valuable pathological predictor for the prognosis in GI mesenchymal neoplasms.

A Histopathological Analysis of 69 Cases of Adenocarcinoma of the Uterine Cervix.: Na Hye Myong, Chang Won Ha, Kyung Ja Cho, Ja June Jang; Korean J Pathol. 1991;25(5):427-435.

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Abstract: Cervical adenocarcinoma represents approximately 3-6% of the uterine cervical neoplasms. Recently, its relative incidence tends to be increased in contrast to squamous cell carcinoma. Sixty nine cases from 1985 to 1990 diagonsed as adenocarcinoma of the cervix by radical or total hysterectomy were analyzed to know their histopathological characteristics and related prognostic factors. The results wer as follows. (1) The age distribution ranged from 24 to 60 years and the mean age was 44 years and 47 years in adenocarcinoma in situ and invasive adenocarcinoma, respectively. Staging by FIGO classification showed the range from stage 0 to IIb, of which 63.8% was stage Ib. (2) Cases were composed of 7 cases of adenocarcinoma in situ(10%) and 62 cases of invasive adenocarcinomas(90%). The latter included 16 cases of adenosquamous carcinoma and 46 cases of pure adenocarcinoma which showed endocervical, endometrioid, clear cell, minimal deviation adenocarcinoma subtypes. The most frequent subtype was endocervical adenocarcinoma(51%) and the endometrioid subtype showed slightly higher incidence rate(13%) in comparison to the previous studies. (3) Coexistent squamous lesions ranging from mild dysplasia to invasive carcinoma were found in 4 out of 7 cases(57%) of adenocarcinoma in situ and 18 out of 62 cases(29%) of invasive adenocarcinoma. Severe dysplasia and carcinoma in situ comprised most(77%) of them. (4) Analyses of histopathological and clinical characteristics of adenocarcinoma of the uterine cervix revealed positive correlations between tumor size or mucin leakage and depth of invasion. The prognostic factors in relation to lymph node metastasis were considered to be th stage of disease, the size of tumor, mucin leakage in the stroma, and histologic subtypes.

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