Journal of Pathology and Translational Medicine

Original Articles

Expression of prostate-specific membrane antigen in the neovasculature of primary tumors and lymph node metastasis of laryngeal squamous cell carcinomas: Gamze Erkılınç, Hasan Yasan, Yusuf Çağda Kumbul, Mehmet Emre Sivrice, Meltem Durgun; J Pathol Transl Med. 2022;56(3):134-143. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.02.22

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Background
Prostate-specific membrane antigen (PSMA) expression is encountered in tumor-associated neovascularization.
Methods
PSMA-antibody was applied to the paraffin blocks of 51 patients who were diagnosed with squamous cell carcinoma of the larynx and underwent laryngectomy and one who underwent lymph node dissection. The percentage of vascular expression in tumoral and extratumoral stroma and lymph nodes and intensity score in tumoral epithelium were evaluated and divided into groups according to the level of PSMA expression. Final PSMA expression was determined by multiplying intensity and percentage scores.
Results
The mean age was 61±10 years. Patients with perineural invasion, cartilage invasion, and local invasion exhibited higher PSMA expression scores. Age, tumor differentiation, tumor diameter, perineural invasion, tumor localization, capsular invasion, depth of invasion, surgical margin status, local invasion, nodal metastasis, TNM classification, and stage were similar in high and low PSMA expression groups. There was no PSMA expression in extratumoral vascular stroma. Significantly higher PSMA expression was observed in the vascular endothelium of metastatic lymph nodes compared with reactive lymph nodes. Patients with advanced-stage disease exhibited higher PSMA vascular expression scores compared to those with earlier stages (p<.001). PSMA expression was not correlated with overall survival, disease-specific survival, or disease-free survival (p>.05).
Conclusions
Our study suggests that higher PSMA expression is associated with cartilage invasion, local invasion, and advanced-stage of disease. PSMA expression can be utilized for detection of lymph node metastasis and has some predictive role in cases of neck metastasis.

Citations

Citations to this article as recorded by

A Practical Guide to the Pearls and Pitfalls of PSMA PET Imaging
Andrew F. Voter, Rudolf A. Werner, Hatice Savas, Andrei Gafita, Ashley E. Ross, Michael A. Gorin, Lilja B. Solnes, Martin G. Pomper, Steven P. Rowe, Sara Sheikhbahaei
Seminars in Nuclear Medicine.2024; 54(1): 119. CrossRef
p53 and PTEN expression evaluation with molecular evident recent criteria in laryngeal carcinoma
Ayca Tan, Gorkem Eskiizmir, Ugur Kamiloglu, Sulen Sarioglu
Medicine.2023; 102(19): e33676. CrossRef
Diagnostic, Prognostic, and Therapeutic Role for Angiogenesis Markers in Head and Neck Squamous Cell Carcinoma: A Narrative Review
Lara Alessandrini, Laura Astolfi, Antonio Daloiso, Marta Sbaraglia, Tiziana Mondello, Elisabetta Zanoletti, Leonardo Franz, Gino Marioni
International Journal of Molecular Sciences.2023; 24(13): 10733. CrossRef

Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma: Myung-Giun Noh, Sung Sun Kim, Eu Chang Hwang, Dong Deuk Kwon, Chan Choi; J Pathol Transl Med. 2017;51(4):365-373. Published online June 9, 2017; DOI: https://doi.org/10.4132/jptm.2017.05.04

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Abstract PDF

Background
Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma.
Methods
The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data.
Results
YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10) than in carcinomas with a low Gleason grades (6–7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)–free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model.
Conclusions
The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

Citations

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Connecting Hippo Pathway and Cytoophidia in Drosophila Posterior Follicle Cells
Rui-Yu Weng, Lei Zhang, Ji-Long Liu
International Journal of Molecular Sciences.2024; 25(3): 1453. CrossRef
NEK1-Mediated Phosphorylation of YAP1 Is Key to Prostate Cancer Progression
Ishita Ghosh, Md Imtiaz Khalil, Rusella Mirza, Judy King, Damilola Olatunde, Arrigo De Benedetti
Biomedicines.2023; 11(3): 734. CrossRef
Epigenetic Inheritance From Normal Origin Cells Can Determine the Aggressive Biology of Tumor-Initiating Cells and Tumor Heterogeneity
Jiliang Feng, Dawei Zhao, Fudong Lv, Zhongyu Yuan
Cancer Control.2022; 29: 107327482210781. CrossRef
A Yes-Associated Protein (YAP) and Insulin-Like Growth Factor 1 Receptor (IGF-1R) Signaling Loop Is Involved in Sorafenib Resistance in Hepatocellular Carcinoma
Mai-Huong T. Ngo, Sue-Wei Peng, Yung-Che Kuo, Chun-Yen Lin, Ming-Heng Wu, Chia-Hsien Chuang, Cheng-Xiang Kao, Han-Yin Jeng, Gee-Way Lin, Thai-Yen Ling, Te-Sheng Chang, Yen-Hua Huang
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Evidence for discrete modes of YAP1 signaling via mRNA splice isoforms in development and diseases
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Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers
Andreas Marx, Aljoscha Schumann, Doris Höflmayer, Elena Bady, Claudia Hube-Magg, Katharina Möller, Maria Christina Tsourlakis, Stefan Steurer, Franziska Büscheck, Till Eichenauer, Till S. Clauditz, Markus Graefen, Ronald Simon, Guido Sauter, Jakob R. Izbi
Scientific Reports.2020;[Epub] CrossRef
NEK1 Phosphorylation of YAP Promotes Its Stabilization and Transcriptional Output
Md Imtiaz Khalil, Ishita Ghosh, Vibha Singh, Jing Chen, Haining Zhu, Arrigo De Benedetti
Cancers.2020; 12(12): 3666. CrossRef

Review & Perspective

Intraductal Carcinoma of Prostate: A Comprehensive and Concise Review: Jordan A. Roberts, Ming Zhou, Yong Wok Park, Jae Y. Ro; Korean J Pathol. 2013;47(4):307-315. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.307

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Abstract PDF

Intraductal carcinoma of the prostate (IDC-P) is defined as a proliferation of prostate adenocarcinoma cells distending and spanning the lumen of pre-existing benign prostatic ducts and acini, with at least focal preservation of basal cells. Studies demonstrate that IDC-P is strongly associated with high-grade (Gleason grades 4/5), large-volume invasive prostate cancers. In addition, recent genetic studies indicate that IDC-P represents intraductal spread of invasive carcinoma, rather than a precursor lesion. Some of the architectural patterns in IDC-P exhibit architectural overlap with one of the main differential diagnoses, high-grade prostatic intraepithelial neoplasia (HGPIN). In these instances, additional diagnostic criteria for IDC-P, including marked nuclear pleomorphism, non-focal comedonecrosis (>1 duct showing comedonecrosis), markedly distended normal ducts/acini, positive nuclear staining for ERG, and cytoplasmic loss of PTEN by immunohistochemistry, can help make the distinction. This distinction between IDC-P and HGPIN is of critical importance because IDC-P has an almost constant association with invasive carcinoma and has negative clinical implications, including shorter relapse-free survival, early biochemical relapse, and metastatic failure rate after radiotherapy. Therefore, IDC-P should be reported in prostate biopsies and radical prostatectomies, regardless of the presence of an invasive component. This article will review the history, diagnostic criteria, molecular genetics, and clinical significance of IDC-P.

Citations

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Detection limits of significant prostate cancer using multiparametric MR and digital rectal examination in men with low serum PSA: Up-date of the Italian Society of Integrated Diagnostic in Urology
Andrea B. Galosi, Erika Palagonia, Simone Scarcella, Alessia Cimadamore, Vito Lacetera, Rocco F. Delle Fave, Angelo Antezza, Lucio Dell'Atti
Archivio Italiano di Urologia e Andrologia.2021; 93(1): 92. CrossRef
Prostate cancer with comedonecrosis is frequently, but not exclusively, intraductal carcinoma: a need for reappraisal of grading criteria
Raghav Madan, Mustafa Deebajah, Shaheen Alanee, Nilesh S Gupta, Shannon Carskadon, Nallasivam Palanisamy, Sean R Williamson
Histopathology.2019; 74(7): 1081. CrossRef
The impact of intraductal carcinoma of the prostate on the site and timing of recurrence and cancer‐specific survival
Vincent Q. Trinh, Jennifer Sirois, Nazim Benzerdjeb, Babak K. Mansoori, Andrée‐Anne Grosset, Roula Albadine, Mathieu Latour, Anne‐Marie Mes‐Masson, Hélène Hovington, Alain Bergeron, Martin Ladouceur, Yves Fradet, Fred Saad, Dominique Trudel
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Comedonecrosis Revisited
Samson W. Fine, Hikmat A. Al-Ahmadie, Ying-Bei Chen, Anuradha Gopalan, Satish K. Tickoo, Victor E. Reuter
American Journal of Surgical Pathology.2018; 42(8): 1036. CrossRef
Focal Signet Ring Cell High-Grade Prostatic Intraepithelial Neoplasia on Needle Biopsy
Guang-Qian Xiao, Pamela D. Unger
International Journal of Surgical Pathology.2017; 25(4): 344. CrossRef
Exposure to maternal obesogenic diet worsens some but not all pre-cancer phenotypes in a murine genetic model of prostate cancer
Theresa Okeyo-Owuor, Emily Benesh, Scott Bibbey, Michaela Reid, Jacques Halabi, Siobhan Sutcliffe, Kelle Moley, Shree Ram Singh
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Histopathological features of intra-ductal carcinoma of prostatic and high grade prostatic intraepithelialneoplasia and correlation with PTEN and P63
Simin Torabi-Nezhad, Leila Malekmakan, Mohadese Mashayekhi, Arghavan Daneshian
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Intraduktales Karzinom der Prostata
G. Kristiansen, M. Varma, G. Seitz
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A Better Understating of the Morphological Features and Molecular Characteristics of Intraductal Carcinoma Helps Clinicians Further Explain Prostate Cancer Aggressiveness
Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Francesco Montorsi
European Urology.2015; 67(3): 504. CrossRef
Clinicopathological analysis of intraductal proliferative lesions of prostate: intraductal carcinoma of prostate, high-grade prostatic intraepithelial neoplasia, and atypical cribriform lesion
Kosuke Miyai, Mukul K. Divatia, Steven S. Shen, Brian J. Miles, Alberto G. Ayala, Jae Y. Ro
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Original Article

ERG Immunohistochemistry and Clinicopathologic Characteristics in Korean Prostate Adenocarcinoma Patients: Ja Hee Suh, Jeong-Whan Park, Cheol Lee, Kyung Chul Moon; Korean J Pathol. 2012;46(5):423-428. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.423

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Abstract PDF

Background

Transmembrane protease serine 2-ETS related gene (TMPRSS2-ERG) gene fusion, the most common genetic alternation in prostate cancer, is associated with protein expression of the oncogene ERG. Recently, an immunohistochemical staining method using an anti-ERG antibody was shown to have a strong correlation with altered ERG protein expression.

Methods

We analyzed a total of 303 radical prostatectomy specimens (obtained from Korean prostate cancer cases) using a constructed tissue microarray and ERG immunohistochemical staining. Thereafter, we evaluated the association between ERG expression and clinicopathological factors.

Results

The ERG-positive rate was 24.4% (74/303) and significantly higher ERG expression was observed in the subgroup with a lower Gleason score (p=0.004). Analysis of the histologic pattern of prostate adenocarcinomas revealed that tumors with discrete glandular units (Gleason pattern 3) displayed higher frequency of ERG expression (p=0.016). The ERG-positive rate was lower than that found (approximately 50%) in studies involving western populations. Other factors including age, tumor volume, initial protein-specific antigen level, a pathological stage and margin status were not significantly related with the ERG expression.

Conclusions

ERG immunohistochemical staining is significantly higher in tumors with well-formed glands and is associated with a lower Gleason score.

Citations

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The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples
Priscilla Mariana Freitas Aguiar Feitosa, Carlos Gustavo Hirth, Isabelle Joyce De Lima Silva‐Fernandes, Conceição Aparecida Dornelas
APMIS.2023; 131(9): 465. CrossRef
Application and Pitfalls of Immunohistochemistry in Diagnosis of Challenging Genitourinary Cases
Jenny Ross, Guangyuan Li, Ximing J. Yang
Archives of Pathology & Laboratory Medicine.2020; 144(3): 290. CrossRef
ERG expression in prostate cancer: diagnostic significance and histopathological correlations
ManarA Abdel-Rahman, HanyO Habashy
Egyptian Journal of Pathology.2020; 40(2): 212. CrossRef
The expression profile and heterogeneity analysis of ERG in 633 consecutive prostate cancers from a single center
Ling Nie, Xiuyi Pan, Mengni Zhang, Xiaoxue Yin, Jing Gong, Xueqin Chen, Miao Xu, Qiao Zhou, Ni Chen
The Prostate.2019; 79(8): 819. CrossRef
MiR-1271 Inhibits Cell Growth in Prostate Cancer by Targeting ERG
Miao Wang, Wei Gao, Dehong Lu, Lianghong Teng
Pathology & Oncology Research.2018; 24(2): 385. CrossRef
Ethnicity and ERG frequency in prostate cancer
Jason Sedarsky, Michael Degon, Shiv Srivastava, Albert Dobi
Nature Reviews Urology.2018; 15(2): 125. CrossRef
The Role of Immunohistochemical Analysis as a Tool for the Diagnosis, Prognostic Evaluation and Treatment of Prostate Cancer: A Systematic Review of the Literature
Arie Carneiro, Álan Roger Gomes Barbosa, Lucas Seiti Takemura, Paulo Priante Kayano, Natasha Kouvaleski Saviano Moran, Carolina Ko Chen, Marcelo Langer Wroclawski, Gustavo Caserta Lemos, Isabela Werneck da Cunha, Marcos Takeo Obara, Marcos Tobias-Machado,
Frontiers in Oncology.2018;[Epub] CrossRef
Prognostic implications of ERG, PTEN, and fatty acid synthase expression in localized prostate cancer
Anan Fathi, Naglaa A. Mostafa, Nabila Hefzi, Khaled A. Mansour
Egyptian Journal of Pathology.2018; 38(1): 162. CrossRef
Intrafocal heterogeneity of ERG protein expression and gene fusion pattern in prostate cancer
Ja Hee Suh, Jeong Hwan Park, Cheol Lee, Kyung Chul Moon
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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
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Correlation of ERG immunohistochemistry with molecular detection of TMPRSS2-ERG gene fusion
Ji-Youn Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, So Young Kang, Yoon-La Choi, Ghee Young Kwon
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Prostate Cancer Prognosis Defined by the Combined Analysis of 8q, PTEN and ERG
Maria P. Silva, João D. Barros-Silva, Elin Ersvær, Wanja Kildal, Tarjei Sveinsgjerd Hveem, Manohar Pradhan, Joana Vieira, Manuel R. Teixeira, Håvard E. Danielsen
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Overexpression of ERG and Wild-Type PTEN Are Associated with Favorable Clinical Prognosis and Low Biochemical Recurrence in Prostate Cancer
Sung Han Kim, Soo Hee Kim, Jae Young Joung, Geon Kook Lee, Eun Kyung Hong, Kyung Min Kang, Ami Yu, Byung Ho Nam, Jinsoo Chung, Ho Kyung Seo, Weon Seo Park, Kang Hyun Lee, Rui Medeiros
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ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients
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Case Report

Metastatic Osteosarcoma to the Prostate: A Case Report.: Hyoung Yeon Seo, Jae Hyuk Lee, Chang Soo Park, Jin Gyoon Park, Sung Taek Jung; Korean J Pathol. 2009;43(5):475-477.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.475

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Abstract PDF: The most common site for the metastasis of osteosarcoma is the lung, and other sites of metastases include the bone, lymph node, pleura and liver. Although unusual extrapulmonary metastases have been reported with the improvement of the therapeutic results for the primary lesions, they are exceptionally rare. We report here on a case of prostatic metastasis of an osteosarcoma of the proximal tibia, and this developed seven years after successful resection, and four years after resection of a pulmonary metastasis. Radical prostatectomy was performed, and histological examination demonstrated metastatic osteosarcoma. To the best of our knowledge, this is the first case of prostatic metastasis of osteosarcoma in the medical literature.

Original Article

The Relationship between the Methylenetetrahydrofolate Reductase Genotypes and the Methylation Status of the CpG Island Loci, LINE-1 and Alu in Prostate Adenocarcinoma.: Jung Ho Kim, Nam Yun Cho, Baek Hee Kim, Wook Youn Kim, Bo Sung Kim, Kyung Chul Moon, Gyeong Hoon Kang; Korean J Pathol. 2009;43(1):26-35.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.26

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Abstract PDF

BACKGROUND
Genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR), in association with the influence of MTHFR upon DNA methylation, may cause differences of the methylation profile of cancer. Thus, we investigated the relationship between the methylation status of prostate adenocarcinoma and the genetic polymorphism of MTHFR.
METHODS
We examined 179 cases of prostate adenocarcinoma for determining the genotypes of MTHFR 677 and 1298, the methylation status of 16 CpG island loci and the methylation levels of the LINE-1 and Alu repeats with using polymerase chain reaction/restriction fragment length polymorphism, methylation-specific polymerase chain reaction and combined bisulphite restriction analysis, respectively.
RESULTS
There was a higher proportion of the CT genotype of MTHFR 677 in the prostate adenocarcinoma than that in the normal control. The TT genotype of MTHFR 677 showed the highest frequency of methylation in six out of nine major CpG island loci, and these were which were frequently hypermethylated in prostate adenocarcinoma. The CT type showed the lowest methylation levels of LINE-1 and Alu among the MTHFR 677 genotypes. Interestingly, the CC type of MTHFR 1298 demonstrated favorable prognostic factors.
CONCLUSIONS
Our study is the first to examine the methylation profile of prostate adenocarcinoma according to the MTHFR genotypes. The differences of the cancer risk, the genomic hypomethylation and the prognosis between the MTHFR genotypes in prostate adenocarcinoma should be further explored.

Citations

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Association Between MTHFR 1298A>C Polymorphism and Spontaneous Abortion with Fetal Chromosomal Aneuploidy
Shin Young Kim, So Yeon Park, Ji Won Choi, Do Jin Kim, Shin Yeong Lee, Ji Hyae Lim, Jung Yeol Han, Hyun Mee Ryu, Min Hyoung Kim
American Journal of Reproductive Immunology.2011; 66(4): 252. CrossRef
Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences
Pornrutsami Jintaridth, Apiwat Mutirangura
Physiological Genomics.2010; 41(2): 194. CrossRef

Case Reports

Fine Needle Aspiration Cytology of Metastatic Prostatic Adenocarcinoma, Pseudohyperplastic Variant.: Youngmee Kwon, Won Seo Park, Geon Kook Lee, Eun Kyung Hong; Korean J Cytopathol. 2008;19(2):183-187.; DOI: https://doi.org/10.3338/kjc.2008.19.2.183

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Abstract PDF: Pseudohyperplastic prostatic adenocarcinoma is a rare histologic variant of prostatic adenocarcinoma that resembles benign nodular hyperplasia. Immunohistochemistry can verify the absence of basal cells, but it is frequently admixed with conventional adenocarcinoma. Because fine needle aspiration cytology is rarely performed in primary prostatic adenocarcinoma, the cytology of the pseudohyperplastic variant has not been described. We experienced a case of metastatic pseudohyperplastic adenocarcinoma in a pulmonary nodule of 75-year-old man. The cytologic smear was mostly composed of large, flat sheets with elongated branching papillae in a clean background. The sheets showed a well-defined honeycomb appearance of tall columnar, regularly arranged monotonous cells with little cytologic atypia. In subsequent prostatic biopsy, pseudohyperplastic variants were identified together with conventional adenocarcinoma of Gleason's grade 3 and 4. The cytologic features of pulmonary nodules were identical to those of pseudohyperplastic components of prostatic adenocarcinoma.

Sarcomatoid Carcinoma with Heterologous Osteosarcomatous Component of the Prostate: A case report.: Eun Sun Jung, Young Jin Choi, Seok Jin Kang, Byung Gee Kim, Sun Moo Kim, Sang In Shim; Korean J Pathol. 1996;30(12):1144-1149.

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Abstract PDF: Sarcomatoid carcinoma of prostate has been rarely reported and occasionally difficult to distinguish from a true sarcoma or carcinosarcoma. A case of sarcomatoid carcinoma of the prostate, which has been occured in 61-year-old male patient is presented. The tumor consists of carcinomatous areas with epithelioid cells, sarcomatoid areas with spindle cells and foci of heterologous osteosarcoma component. The phenotypic nature of the tumor was confirmed immunohistochemically by positive reaction for cytokeratin, epithelial membrane antigen, vimentin and prostate specific acid phosphatase in both sarcomatous and carcinomatous components.

Original Articles

Immunohistochemical Evaluation of Cathepsin D, MMP-2, and TIMP in Prostate Carcinoma.: Jung Weon Shim, Soon Ran Kim, Yun Jung Kim, Hye Kyung Ahn, Young Euy Park, Sung Sook Kim, Min Young Kim; Korean J Pathol. 1997;31(4):342-350.

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Abstract PDF: Twenty six cases of primary adenocarcinoma of the prostate, ranging from 4 to 9 according to Gleason's summing score, were studied. Immunoreactivity was evaluated using the rabbit polyclonal anti-Cathepsin D antibody (CD), a mouse monoclonal MMP-2 antibody (MMP-2), and a tissue inhibitor metalloproteinase (TIMP) in formalin-fixed, paraffin-embedded prostatic tissue. Immunohistochemical staining was scored by summing the intensity of staining (0 to 3+) weighted by the percentage of tumor staining at each intensity (H score, theoretical range 0 to 300). For CD, the tumor cells showed diffuse cytoplasmic immunoreactivity in all 26 cases (100%). For MMP-2 the tumor cells showed cytoplasmic immunoreactivity in 17 of 26 cases (65.38%). As the Gleason grade increased the expression of CD increased (P=0.0027). The reactivity of CD was significantly correlated with the Gleason's score (R=0.65637), but, the reactivity of MMP-2 was not correlated. There were no significant correlations between each of the CD and the MMP-2 scores, and stage. TIMP expression was predominantly localized in the stroma rather than in the cancer cells themselves. We believe that 1) CD and MMP-2, both immunohistochemically detectable in a majority of prostate adenocarcinoma, may play a role in determination of the invasive or metastatic property, 2) the enhanced TIMP expression in the stroma may be associated with the response to cancer invasion.

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.

Estrogen and Progesterone Receptor Expressions in Benign Prostatic Hypertrophy and Prostatic Adenocarcinoma.: Mi Seon Kang, Seo Young Park, Hye Kyoung Yoon; Korean J Pathol. 1998;32(5):346-351.

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Abstract: The effect of androgen in the development of the normal prostate and the evolution of benign prostatic hypertrophy (BPH), and prostatic adenocarcinoma has been proven. In addition to androgen, estrogen and progesterone are also thought to play a role in the pathogenesis of BPH and carcinoma. However, their exact roles are not yet known because there is no conclusive evidence. Thirty cases of prostatic adenocarcinoma and 16 cases of BPH were studied. Immunohistochemical staining for estrogen receptor (ER) and progesterone receptor (PR) in epithelial and stromal cells, respectively was performed and the results were assessed semiquantitatively based on the number of positive cells per 100 total cells. Slides were scored as negative; less than 5% of cells, 1 ; 6~15% of cells, 2 ; 16~25% of cells, and 3 ; more than 26% of cells. The relationship between ER and PR expression and the patient's age, histologic grade, and clinical stage was evaluated in prostatic adenocarcinomas. ER was negative in epithelial and in stromal cells for all prostatic adenocarcinomas and BPH cases. The PR expression in epithelial cells and in stromal cells of BPH was noted in 15 (93.8%) and 16 (100.0%) out of 16, respectively. The PR expression of carcinoma cells and stromal cells in prostatic adenocarcinoma was found in 28 (93.3%) and 23 out of 30 (76.7%), respectively. The PR immunoreactivities of stromal cells around carcinoma were 3 in 18 cases, 2 in one case, and 1 in 4 cases, but those of epithelial and stromal cells of BPH and carcinoma cells of prostatic carcinoma were similar to each other with a value of 3 in most cases. The PR expression rate of stromal cells around carcinoma was significantly correlated with the patient's age (p=0.044), but not with histologic grade and clinical stage. In summary, estrogen does not have a direct effect on the biological behavior of BPH and prostatic adenocarcinoma, but progesterone appears to play a role in the pathogenesis of BPH and prostatic adenocarcinoma. Further studies should clarify the biological role of progesterone in the human prostate.

Castration-induced Apoptosis in the Rat Prostate.: Ki Kwon Kim, Sang Sook Lee; Korean J Pathol. 1998;32(6):431-442.

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Abstract: This study was carried out to investigate the morphologic findings and process of castration-induced apoptosis in the rat prostate. The experimental group was treated with bilateral orchiectomy followed by sequential sacrifices at 1, 2, 3, 4, 5, 6, 7 days and 2, 3 weeks (6 rats, respectively). Ventral prostate was extirpated and examined by light microscopic and immunohistochemical, ultrastructural observation. Apoptotic index increased by 4 days after castration and decreased thereafter. ApopTag stain revealed brownish granular pattern in the nucleus of apoptotic cells. DNA fragmentation rate was 0.5% in the control group and began to increase by 1 day after castration and reached to 11.1% by 4 days and decreased thereafter. PCNA stain showed brownish granular pattern in the nucleus of some epithelial cells of the prostatic glands. PCNA labelling index was 2.4% in the control group and reached peak by 3 days after castration and decreased thereafter. Electron microscopically, there was chromatin condensation with margination toward the nuclear membrane by 1 day after castration. Also noted were condensation of cytoplasm, dilatation of RER and nuclear fragmentation. Apoptotic bodies were formed and phagocytosed by adjacent cells and some apoptotic bodies were found in the lumen of acini. Based on these results, it can be concluded that castration-induced prostatic involution is the result of apoptosis. Detection of DNA fragmentation with ApopTag is a more a accurate method to identify not only apoptotic body formation itself but also the previous step of apoptotic body formation. PCNA labelling index to identify the cellular proliferation seems to play an active role in the early step of apoptosis and be a good tool for investigation of apoptosis.

Case Reports

Signet Ring Cell Carcinoma of the Prostate A report of two cases.: Yu Na Kang, Sang Sook Lee, Tae Jin Lee, Jae Yoon Ro; Korean J Pathol. 1999;33(5):385-368.

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Abstract PDF: Primary signet ring cell carcinoma of the prostate is extremely rare and about 18 cases have been reported in the literature. We report two cases of primary signet ring cell carcinoma of the prostate, arising in 79-year-old and 65-year-old men. Both cases were the poorly differentiated adenocarcinoma of the prostate with many signet ring cells. Signet ring cells were positive for prostatic specific antigen and prostatic acid phosphatase but negative for neutral and acid mucins. In summary, the signet ring cell carcinoma of the prostate is a rare variant of poorly differentiated adenocarcinoma of the prostate. The orgin of the prostate should be considered in cases of metastatic signet ring cell carcinoma, particularly when the signet ring cells are negative for neutral and acid mucins. Prostatic specific antigen and prostatic acid phosphatase should also be performed to confirm the primary signet ring cell carcinoma of the prostate.

Verumontanum Mucosal Gland Hyperplasia: A case report.: Mi Sun Choe, Tae Jin Lee, Eun Sil Yu, Jae Y Ro; Korean J Pathol. 1999;33(9):737-740.

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Abstract PDF: Verumontanum mucosal gland hyperplasia (VMGH) is a relatively common benign proliferative lesion which was first described by Gagucas et al in 1995. VMGH is usually found in radical prostatectomy or transurethral resection specimens and rarely in needle biopsy specimens. The histologic feature of VMGH is characterized by well-circumscribed proliferation of small glands and thus VMGH may mimic low grade adenocarcinoma. We report a case of VMGH from a 61-year-old man. The lesion coexisted with prostatic adenocarcinoma on radical prostatectomy specimen. The lesion was a well circumscribed microacinar proliferation which was present between the openings of ejaculatory ducts. The acini consisted of two cell layers with inner secretory cuboidal epithelium and outer basal cell. Typically, the lumen contained many corpora amylacea. Nuclear pleomorphism, prominent nucleolus, or mitotic figure was not identified. Because of small gland proliferation of VMGH, this lesion can be confused with other small gland proliferative lesions, such as low grade adenocarcinoma, atypical adenomatous hyperplasia, basal cell hyperplasia, mesonephric hyperplasia, and nephrogenic adenoma. To avoid misdiagnosis of VMGH as carcinoma, one should be familiar with this lesion.

Original Article

Prostatic Intraepithelial Neoplasia in Transurethral Resection Specimens On serum PSA and histologic findings.: Joon Mee Kim, Soo Kee Min, Young Chae Chu, Tae Sook Hwang, Young Bae Kim, Jee Young Han, Tae Sook Kim, Hye Seung Han; Korean J Pathol. 2000;34(5):349-357.

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Abstract PDF: Prostatic intraepithelial neoplasia (PIN), which is divided into low and high grade, has different clinicopathologic significance. We reviewed 158 prostatic tissues, which consisted of 144 cases of nodular hyperplasias and 14 cases of adenocarcinomas, to evaluate incidence of PIN, its histologic finding, and its clinical significance. Ten cases of PIN, 4 low grade and 6 high grade, were found. Four cases of low grade PIN (LPIN) and five cases of high grade PIN (HPIN) were associated with nodular hyperplasia. Only one case of HPIN occurred in carcinoma. The constant histologic findings of LPIN were nuclear stratification and nucleomegaly. The most prominent characteristics of HPIN were hyperchromasia and prominent nucleoli. Anisonucleosis was not so helpful for differential diagnosis between LPIN and HPIN. Basal layer disruption was present in one case of high grade PIN associated with adenocarcinoma, and important for the differentiatial diagnosis of cribriform HPIN from the cribriform adenocarcinoma. There was no significant difference in age incidence between the two groups with the mean age of 70.9 years in nodular hyperplasia and 69.4 years in adenocarcinoma. Serum PSA level was significantly different between the two group with the mean PSA value of 11.03 ng/ml in nodular hyperplasia and that of 73.76 ng/ml in carcinoma (p=0.000). However, PSA values between "nodular hyperplasia only" group and "PIN associated nodular hyperplasia" group were not significantly different. PIN association changed neither age distribution nor serum PSA level. During the follow up period, no adenocacinoma has occurred in the cases having PIN although serum PSA level has elevated in some cases. One case of adenocarcinoma associated with HPIN developed in the nodular hyperplasia patient. Although PIN did not increase the possibility of subsequent prostatic adenocarcinoma in transurethral resection specimens, it could not be excluded that PIN was a precursor of prostatic adenocarcinoma.

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