Journal of Pathology and Translational Medicine

Original Articles

Diverse Immunoprofile of Ductal Adenocarcinoma of the Prostate with an Emphasis on the Prognostic Factors: Se Un Jeong, Anuja Kashikar Kekatpure, Ja-Min Park, Minkyu Han, Hee Sang Hwang, Hui Jeong Jeong, Heounjeong Go, Yong Mee Cho; J Pathol Transl Med. 2017;51(5):471-481. Published online August 9, 2017; DOI: https://doi.org/10.4132/jptm.2017.06.02

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Background
Ductal adenocarcinoma (DAC) of the prostate is an uncommon histologic subtype whose prognostic factors and immunoprofile have not been fully defined. Methods: To define its prognostic factors and immunoprofile, the clinicopathological features, including biochemical recurrence (BCR), of 61 cases of DAC were analyzed. Immunohistochemistry was performed on tissue microarray constructs to assess the expression of prostate cancer-related and mammalian target of rapamycin (mTOR) signaling-related proteins. Results: During the median follow-up period of 19.3 months, BCR occurred in 26 cases (42.6%). DAC demonstrated a wide expression range of prostate cancer-related proteins, including nine cases (14.8%) that were totally negative for pan-cytokeratin (PanCK) immunostaining. The mTOR signaling-related proteins also showed diverse expression. On univariate analysis, BCR was associated with high preoperative serum levels of prostate-specific antigen (PSA), large tumor volume, predominant ductal component, high Gleason score (GS), comedo-necrosis, high tumor stage (pT), lymphovascular invasion, and positive surgical margin. High expressions of phospho-mTOR (p-mTOR) as well as low expressions of PSA, phospho-S6 ribosomal protein (pS6) and PanCK were associated with BCR. On multivariable analysis, GS, pT, and immunohistochemical expressions of PanCK and p-mTOR remained independent prognostic factors for BCR. Conclusions: These results suggest GS, pT, and immunohistochemical expressions of PanCK and p-mTOR as independent prognostic factors for BCR in DAC. Since DAC showed diverse expression of prostate cancer–related proteins, this should be recognized in interpreting the immunoprofile of DAC. The diverse expression of mTOR-related proteins implicates their potential utility as predictive markers for mTOR targeted therapy.

Citations

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Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review
Giancarlo Marra, Geert J.L.H. van Leenders, Fabio Zattoni, Claudia Kesch, Pawel Rajwa, Philip Cornford, Theodorus van der Kwast, Roderick C.N. van den Bergh, Erik Briers, Thomas Van den Broeck, Gert De Meerleer, Maria De Santis, Daniel Eberli, Andrea Faro
European Urology.2023; 84(1): 65. CrossRef
Impact of comedonecrosis on prostate cancer outcome: a systematic review
Kaveri T S Aiyer, Lisa J Kroon, Geert J L H van Leenders
Histopathology.2023; 83(3): 339. CrossRef
High GLUT1 membrane expression and low PSMA membrane expression in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate
Xingming Wang, Li Zhou, Lin Qi, Ye Zhang, Hongling Yin, Yu Gan, Xiaomei Gao, Yi Cai
Prostate Cancer and Prostatic Diseases.2023;[Epub] CrossRef
Survival after radical prostatectomy vs. radiation therapy in ductal carcinoma of the prostate
Francesco Chierigo, Marco Borghesi, Christoph Würnschimmel, Rocco Simone Flammia, Benedikt Horlemann, Gabriele Sorce, Benedikt Höh, Zhe Tian, Fred Saad, Markus Graefen, Michele Gallucci, Alberto Briganti, Francesco Montorsi, Felix K. H. Chun, Shahrokh F.
International Urology and Nephrology.2022; 54(1): 89. CrossRef
Defining Diagnostic Criteria for Prostatic Ductal Adenocarcinoma at Multiparametric MRI
Weranja K. B. Ranasinghe, Patricia Troncoso, Devaki Shilpa Surasi, Juan José Ibarra Rovira, Priya Bhosale, Janio Szklaruk, Andrea Kokorovic, Xuemei Wang, Mohamed Elsheshtawi, Miao Zhang, Ana Aparicio, Brian F. Chapin, Tharakeswara K. Bathala
Radiology.2022; 303(1): 110. CrossRef
Oncological outcomes of patients with ductal adenocarcinoma of the prostate receiving radical prostatectomy or radiotherapy
Mengzhu Liu, Kun Jin, Shi Qiu, Pengyong Xu, Mingming Zhang, Wufeng Cai, Xiaonan Zheng, Lu Yang, Qiang Wei
Asian Journal of Urology.2021; 8(2): 227. CrossRef
Ductal Prostate Cancers Demonstrate Poor Outcomes with Conventional Therapies
Weranja Ranasinghe, Daniel D. Shapiro, Hyunsoo Hwang, Xuemei Wang, Chad A. Reichard, Mohamed Elsheshtawi, Mary F. Achim, Tharakeswara Bathala, Chad Tang, Ana Aparicio, Shi-Ming Tu, Nora Navone, Timothy C. Thompson, Louis Pisters, Patricia Troncoso, John W
European Urology.2021; 79(2): 298. CrossRef
Optimizing the diagnosis and management of ductal prostate cancer
Weranja Ranasinghe, Daniel D. Shapiro, Miao Zhang, Tharakeswara Bathala, Nora Navone, Timothy C. Thompson, Bradley Broom, Ana Aparicio, Shi-Ming Tu, Chad Tang, John W. Davis, Louis Pisters, Brian F. Chapin
Nature Reviews Urology.2021; 18(6): 337. CrossRef
A first case of ductal adenocarcinoma of the prostate having characteristics of neuroendocrine phenotype with PTEN, RB1 and TP53 alterations
Hiroaki Kobayashi, Takeo Kosaka, Kohei Nakamura, Kazunori Shojo, Hiroshi Hongo, Shuji Mikami, Hiroshi Nishihara, Mototsugu Oya
BMC Medical Genomics.2021;[Epub] CrossRef
Knowing what’s growing: Why ductal and intraductal prostate cancer matter
Mitchell G. Lawrence, Laura H. Porter, David Clouston, Declan G. Murphy, Mark Frydenberg, Renea A. Taylor, Gail P. Risbridger
Science Translational Medicine.2020;[Epub] CrossRef
Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer
Marc Gillard, Justin Lack, Andrea Pontier, Divya Gandla, David Hatcher, Adam G. Sowalsky, Jose Rodriguez-Nieves, Donald Vander Griend, Gladell Paner, David VanderWeele
European Urology Focus.2019; 5(3): 433. CrossRef
Genomic Characterization of Prostatic Ductal Adenocarcinoma Identifies a High Prevalence of DNA Repair Gene Mutations
Michael T. Schweizer, Emmanuel S. Antonarakis, Tarek A. Bismar, Liana B. Guedes, Heather H. Cheng, Maria S. Tretiakova, Funda Vakar-Lopez, Nola Klemfuss, Eric Q. Konnick, Elahe A. Mostaghel, Andrew C. Hsieh, Peter S. Nelson, Evan Y. Yu, R. Bruce Montgomer
JCO Precision Oncology.2019; (3): 1. 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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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

Uncoupling Protein 2 (UCP2) and p53 Expression in Invasive Ductal Carcinoma of Breast.: Kyu Yeoun Won, Gou Young Kim, Youn Wha Kim, Sung Jig Lim, Jeong Yoon Song; Korean J Pathol. 2010;44(6):565-570.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.565

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Abstract PDF

BACKGROUND
Uncoupling protein 2 (UCP2) is a recently identified mitochondrial inner membrane anion carrier and a negative regulator of reactive oxygen species production. In this study, we evaluated the characteristics and relationships of UCP2 and p53 expression in breast cancer tissues.
METHODS
Tissue microarray slides from 107 cases of invasive ductal carcinoma of the breast were constructed, UCP2 and p53 immunohistochemical staining was conducted, and clinicopathological correlations were investigated.
RESULTS
UCP2 expression in invasive ductal carcinoma was high in 53 cases (49.5%), while p53 expression in invasive ductal carcinoma was high in 37 cases (34.6%). UCP2 expression was correlated significantly with histological grade (p = 0.038) and mitotic count (p = 0.050). UCP2 expression was correlated significantly with p53 expression in invasive ductal carcinoma of the breast (p = 0.045). UCP2 expression (p = 0.8308) and p53 expression (p = 0.3292) showed no significant difference for the overall survival rate in patients with invasive ductal carcinoma.
CONCLUSIONS
UCP2 expression in invasive ductal carcinoma increased proportionally with histological grade and mitotic count. High UCP2 expression in invasive ductal carcinoma was observed in conjunction with high p53 expression.

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Forkhead box protein A1 inhibits the expression of uncoupling protein 2 in hydrogen peroxide-induced A549 cell line
Lan Song, Zhaojun Xu, Ling Li, Mei Hu, Lijuan Cheng, Lingli Chen, Bo Zhang
Cell Stress and Chaperones.2014; 19(1): 53. CrossRef
New Aspects of Mitochondrial Uncoupling Proteins (UCPs) and Their Roles in Tumorigenesis
Delira Robbins, Yunfeng Zhao
International Journal of Molecular Sciences.2011; 12(8): 5285. CrossRef

Changes in Protein Expression in Breast Cancer after Anthracycline-Based Chemotherapy.: Ho chang Lee, Jae Ok Lee, In Ae Park; Korean J Pathol. 2007;41(3):165-170.

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Abstract PDF: Background
: Anthracyclines are the standard agents used to treat patients with advanced breast carcinoma. Some molecules are reportedly associated with anthracycline resistance; however, there has been some controversy surrounding these claims. The gain or loss of certain molecules after chemotherapy can explain the discrepancies in the results.
Methods
: We evaluated the expression levels of the estrogen receptor (ER), p53, and bcl-2 in specimens obtained from twenty patients with advanced breast cancer before and after anthracyclinebased chemotherapy using immunohistochemistry (IHC). We also examined HER2/neu expression in these specimens using IHC and fluorescence in situ hybridization (FISH) analysis.
Results
: After chemotherapy, one of the twenty cases (5%) showed decreased ER expression, one (5%) showed decreased p53 expression, and one (5%) showed increased bcl-2 expression. IHC and FISH analysis in pre- and post-chemotherapy specimens showed that the expression of HER2/neu changed from equivocal to negative in one case (5%).
Conclusion
: Our results showed that the expression levels of HER2/neu, ER, p53 and bcl-2 remained stable after chemotherapy, although the statistical significance of these results may not be validated due to the small number of cases. We also suggested that the resistance to anthracycline-based chemotherapy might not be associated with the modification of these molecules.

Case Report

Synchronous Invasive Ductal Carcinoma and Metastatic Ovarian Serous Papillary Adenocarcinoma in the Same Breast: A Case Report.: Hyun Jung Kim, Sung jig Lim, Sehwan Han, Ji Young Kim, Kyeongmee Park; Korean J Pathol. 2006;40(1):66-69.

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Abstract PDF: A 59-year-old woman displayed multiple palpable right breast masses along with ipsilateral cervical and axillary lymphadenopathy. She had a previous history of bilateral salpingo-oopho- rectomy for serous papillary adenocarcinoma two and half years ago. She underwent mastectomy for the lesions located in the upper inner breast quadrant. A 1 cm-sized primary ductal carcinoma was present; however, the other breast lesions and the metastatic axillary lymph nodes were confirmed as showing papillary serous adenocarcinoma, which were similar to the previous ovarian tumor. After the patient underwent postoperative adjuvant chemotherapy, of 8 cycles of doxorubicin and docetaxel, she has been stable during the clinical follow-up for 10 months with decreases in size of the metastatic nodules.

Original Article

Prognostic Significance of Abnormal beta - catenin Expression in Breast Carcinoma.: Won Ae Lee; Korean J Pathol. 2005;39(2):114-119.

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Abstract PDF: BACKGROUND
The subcellular localization and activity of beta-catenin are tightly regulated within the cell. The aim of this study was to analyze the aberrant beta-catenin expression in breast carcinomas and to determine its clinical significance.
METHODS
Fifty five cases of breast carcinoma were immunostained with monoclonal antibodies against beta-catenin. Normal expression of -catenin was defined as exclusive membranous staining. Abnormal expression of beta-catenin was reclassified into 3 categories: complete or partial loss of membranous staining (LOM) without cytoplasmic staining and nuclear staining, LOM with cytoplasmic staining and without nuclear staining, and LOM with nuclear staining and with/without cytoplasmic staining. RESULTS: Normal membranous beta-catenin expression was detected in 25 (45.5%) of 55 cases of breast carcinoma. Thirty cases with abnormal -catenin expression comprised 9 cases (16.1%) showing LOM without cytoplasmic and/or nuclear staining, 20 cases (36.4%) showing LOM with cytoplasmic staining and without nuclear staining, and one case (1.8%) showing LOM with nuclear and cytoplasmic staining. Abnormal beta-catenin expression was significantly correlated with lymph node metastasis (p=0.03). LOM with cytoplasmic and/or nuclear expression was significantly correlated with poor disease free survival by univariate (p=0.03) and multivariate analyses (p=0.03). In addition, it was correlated with poor overall survival with a borderline significance (p=0.059).
CONCLUSIONS
This study suggests that the cytoplasmic and/or nuclear expression of beta-catenin can be used as a biologic marker for predicting disease recurrence and poor patients' survival in breast carcinomas.

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