Journal of Pathology and Translational Medicine

Original Articles

Analysis of the molecular subtypes of preoperative core needle biopsy and surgical specimens in invasive breast cancer: Ye Sul Jeong, Jun Kang, Jieun Lee, Tae-Kyung Yoo, Sung Hun Kim, Ahwon Lee; J Pathol Transl Med. 2020;54(1):87-94. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.14

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Background
Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens.
Methods
This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary’s Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0–8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers.
Results
In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively.
Conclusions
CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.

Citations

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Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer
Min Chong Kim, Sun Young Kwon, Hye Ra Jung, Young Kyung Bae
Virchows Archiv.2024;[Epub] CrossRef
Study on Intratumoral Heterogeneity of Expression of Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 in Carcinoma Breast
Ragavi Uthayasuriyan, Sheba K Jacob, Saloni Naresh Shah
Apollo Medicine.2024; 21(1): 51. CrossRef
Concordance of HER2 status between core needle biopsy and surgical resection specimens of breast cancer: an analysis focusing on the HER2-low status
Sei Na, Milim Kim, Yujun Park, Hyun Jung Kwon, Hee-Chul Shin, Eun-Kyu Kim, Mijung Jang, Sun Mi Kim, So Yeon Park
Breast Cancer.2024; 31(4): 705. CrossRef
Concordance of immunohistochemistry for predictive and prognostic factors in breast cancer between biopsy and surgical excision: a single-centre experience and review of the literature
Chiara Rossi, Sara Fraticelli, Marianna Fanizza, Alberta Ferrari, Elisa Ferraris, Alessia Messina, Angelica Della Valle, Chiara Annunziata Pasqualina Anghelone, Angioletta Lasagna, Gianpiero Rizzo, Lorenzo Perrone, Maria Grazia Sommaruga, Giulia Meloni, S
Breast Cancer Research and Treatment.2023; 198(3): 573. CrossRef
Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor
Su Hwa Kim, Young Suk Lee, Sung Hak Lee, Yeoun Eun Sung, Ahwon Lee, Jun Kang, Jae-Sung Park, Sin Soo Jeun, Youn Soo Lee
Journal of Pathology and Translational Medicine.2023; 57(4): 217. CrossRef
The Role of Diffusion-Weighted Imaging Based on Maximum-Intensity Projection in Young Patients with Marked Background Parenchymal Enhancement on Contrast-Enhanced Breast MRI
Ga-Eun Park, Bong-Joo Kang, Sung-hun Kim, Na-Young Jung
Life.2023; 13(8): 1744. CrossRef
Concordance between core needle biopsy and surgical excision specimens for Ki‐67 in breast cancer – a systematic review of the literature
Jahnavi Kalvala, Ruth M Parks, Andrew R Green, Kwok‐Leung Cheung
Histopathology.2022; 80(3): 468. CrossRef
İnvaziv Meme Kanserinde Preoperatif Kor İğne Biyopsi ile Postoperatif Cerrahi Spesmenler Arasında ER, PR, HER2 ve Ki67 Açısından Karşılaştırma
Pınar CELEPLİ, Pelin Seher ÖZTEKİN, Salih CELEPLİ, İrem BİGAT, Sema HÜCÜMENOĞLU
Akdeniz Medical Journal.2022; : 179. CrossRef
Concordance of breast cancer biomarker testing in core needle biopsy and surgical specimens: A single institution experience
Jessica A. Slostad, Nicole K. Yun, Aimee E. Schad, Surbhi Warrior, Louis F. Fogg, Ruta Rao
Cancer Medicine.2022; 11(24): 4954. CrossRef
N-Cadherin Distinguishes Intrahepatic Cholangiocarcinoma from Liver Metastases of Ductal Adenocarcinoma of the Pancreas
Tiemo S. Gerber, Benjamin Goeppert, Anne Hausen, Hagen R. Witzel, Fabian Bartsch, Mario Schindeldecker, Lisa-Katharina Gröger, Dirk A. Ridder, Oscar Cahyadi, Irene Esposito, Matthias M. Gaida, Peter Schirmacher, Peter R. Galle, Hauke Lang, Wilfried Roth,
Cancers.2022; 14(13): 3091. CrossRef
Association of Ki-67 Change Pattern After Core Needle Biopsy and Prognosis in HR+/HER2− Early Breast Cancer Patients
Shuai Li, Xiaosong Chen, Kunwei Shen
Frontiers in Surgery.2022;[Epub] CrossRef
MRI Features for Prediction Malignant Intra-Mammary Lymph Nodes: Correlations with Mammography and Ultrasound
Meejung Kim, Bong Joo Kang, Ga Eun Park
Investigative Magnetic Resonance Imaging.2022; 26(2): 135. CrossRef
A single centre experience in Turkey for comparison between core needle biopsy and surgical specimen evaluation results for HER2, SISH, estrogen receptors and progesterone receptors in breast cancer patients
Hatice Karaman, Fatma Senel, Arzu Tasdemir, Ipek Özer, Merve Dogan
Journal of Cancer Research and Therapeutics.2022; 18(6): 1789. CrossRef
Meme kanseri trucut ve rezeksiyon materyallerinde yeni moleküler sınıflama, tanı ve hormon reseptörlerinin durumu tutarlı mı?
Yeliz ARMAN KARAKAYA, Sevda YILMAZ, Hande KARABAŞ
Pamukkale Medical Journal.2021;[Epub] CrossRef
What shear wave elastography parameter best differentiates breast cancer and predicts its histologic aggressiveness?
Hyunjin Kim, Jeongmin Lee, Bong Joo Kang, Sung Hun Kim
Ultrasonography.2021; 40(2): 265. CrossRef
Risk-based decision-making in the treatment of HER2-positive early breast cancer: Recommendations based on the current state of knowledge
Christian Jackisch, Patricia Cortazar, Charles E. Geyer, Luca Gianni, Joseph Gligorov, Zuzana Machackova, Edith A. Perez, Andreas Schneeweiss, Sara M. Tolaney, Michael Untch, Andrew Wardley, Martine Piccart
Cancer Treatment Reviews.2021; 99: 102229. CrossRef
Factors influencing agreement of breast cancer luminal molecular subtype by Ki67 labeling index between core needle biopsy and surgical resection specimens
Kristina A. Tendl-Schulz, Fabian Rössler, Philipp Wimmer, Ulrike M. Heber, Martina Mittlböck, Nicolas Kozakowski, Katja Pinker, Rupert Bartsch, Peter Dubsky, Florian Fitzal, Martin Filipits, Fanny Carolina Eckel, Eva-Maria Langthaler, Günther Steger, Mich
Virchows Archiv.2020; 477(4): 545. CrossRef

Expression of female sex hormone receptors and its relation to clinicopathological characteristics and prognosis of lung adenocarcinoma: Jin Hwan Lee, Han Kyeom Kim, Bong Kyung Shin; J Pathol Transl Med. 2020;54(1):103-111. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.12

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Abstract PDF

Background
Adenocarcinoma (ADC) of the lung exhibits different clinicopathological characteristics in men and women. Recent studies have suggested that these differences originate from the expression of female sex hormone receptors in tumor cells. The aim of the present study was to evaluate the immunohistochemical expression of female sex hormone receptors in lung ADC and determine the expression patterns in patients with different clinicopathological characteristics.
Methods
A total of 84 patients with lung ADC who underwent surgical resection and/or core biopsy were recruited for the present study. Immunohistochemical staining was performed for estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR), epidermal growth factor receptor (EGFR), EGFR E746- A750 del, and EGFR L858R using tissue microarray.
Results
A total of 39 (46.4%) ERα-positive, 71 (84.5%) ERβ-positive, and 46 (54.8%) PR-positive lung ADCs were identified. In addition, there were 81 (96.4%) EGFR-positive, 14 (16.7%) EGFR E746-A750 del–positive, and 34 (40.5%) EGFR L858R–positive cases. The expression of female sex hormone receptors was not significantly different in clinicopathologically different subsets of lung ADC.
Conclusions
Expression of female sex hormone receptors is not associated with the prognosis and clinicopathological characteristics of patients with lung ADC.

Citations

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Molecular characteristics of non-small cell lung cancer tissue based on quantitative indicators of progesterone receptors expression
I. P. Romanov, T. A. Bogush, A. M. Scherbakov, A. A. Alimov, E. A. Bogush, A. B. Ravcheeva, A. Lee, V. S. Kosorukov
Antibiot Khimioter = Antibiotics and Chemotherapy.2024; 69(1-2): 29. CrossRef
Genes Co-Expressed with ESR2 Influence Clinical Outcomes in Cancer Patients: TCGA Data Analysis
Julia Maria Lipowicz, Agnieszka Malińska, Michał Nowicki, Agnieszka Anna Rawłuszko-Wieczorek
International Journal of Molecular Sciences.2024; 25(16): 8707. CrossRef
Complex Differential Diagnosis between Primary Breast Cancer and Breast Metastasis from EGFR-Mutated Lung Adenocarcinoma: Case Report and Literature Review
Carmine Valenza, Francesca Maria Porta, Alessandra Rappa, Elena Guerini-Rocco, Giuseppe Viale, Massimo Barberis, Filippo de Marinis, Giuseppe Curigliano, Chiara Catania
Current Oncology.2021; 28(5): 3384. CrossRef
Development of a 15-Gene Signature Model as a Prognostic Tool in Sex Hormone-Dependent Cancers
Zhi Xia, Jian Xiao, Aibin Liu, Qiong Chen, Arumugam R. Jayakumar
BioMed Research International.2021; 2021: 1. CrossRef
Gender-specific aspects of epidemiology, molecular genetics and outcome: lung cancer
Nuria Mederos, Alex Friedlaender, Solange Peters, Alfredo Addeo
ESMO Open.2020; 5(Suppl 4): e000796. CrossRef

Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects: Natalia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Artem Piddubnyi, Ludmila Karpenko, Olha Kravtsova, Dmytrii Hyriavenko, Olena Diachenko, Vladyslav Sikora, Anatolii Romaniuk; J Pathol Transl Med. 2019;53(4):236-243. Published online April 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.03.21

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Abstract PDF

Background
Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype.
Methods
The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics.
Results
ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy.
Conclusions
Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.

Citations

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Rare non-serous fallopian tube cancers: institutional experience and literature review
Dmitrii Sumtsov, Georgyi Sumtsov, Nataliia Hyriavenko, Mykola Lyndin, Kateryna Sikora, Nataliia Kalashnik, Svitlana Smiian, Igor Gladchuk
Wiener Medizinische Wochenschrift.2024; 174(9-10): 199. CrossRef
UŞAQLIQ BORULARININ BİRİNCİLİ XƏRÇƏNGİ: DİAQNOSTİKASI VƏ MÜALİCƏSİNİN NƏTİCƏLƏRİ
D.G. Sumtsov, G.O. Sumtsov, N.I. Hyriavenko, S.A. Smiian, N.V. Kalashnyk, K.O. Sikora, N.M. Rozhkovska, I.Z. Gladchuk
Azerbaijan Medical Journal.2023; (4): 75. CrossRef
FEATURES OF ENDOMETRIUM STRUCTURE IN ALCOHOL-ABUSING HIV-INFECTED INDIVIDUALS
M. Lytvynenko
Inter Collegas.2021; 8(1): 52. CrossRef
Concurrent Clostridial Enteritis and Oviductal Adenocarcinoma with Carcinomatosis in an Adult Alpaca (Vicugna pacos)
Mandy Womble, Megan E. Schreeg, Allison Hoch, Enoch B. de Souza Meira, Derek Foster, Christopher Premanandan, Tatiane T. Negrão Watanabe
Journal of Comparative Pathology.2021; 189: 52. CrossRef
Problems of primary fallopian tube cancer diagnostics during and after surgery
D.G. Sumtsov, I.Z. Gladchuk, G.O. Sumtsov, N.I. Hyriavenko, M.S. Lyndin, V.V. Sikora, V.M. Zaporozhan
REPRODUCTIVE ENDOCRINOLOGY.2021; (59): 66. CrossRef

Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics: Byung-Kwan Jeong, Chang O. Sung, Kyu-Rae Kim; J Pathol Transl Med. 2019;53(1):31-39. Published online December 18, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.16

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Abstract PDF

Background
Breast cancer treatment with selective estrogen receptor modulators (SERMs) increasesthe incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologiccharacteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discusspossible pathogenetic mechanisms.
Methods
Among 28,104 patients with breast cancer, clinicopathologicfeatures and incidence of uMMMT were compared between patients who underwentSERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period,incidence, dose, and duration of SERM treatment, as well as overall survival rate, were comparedfor patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMTvs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathologicalfindings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ,progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT.
Results
The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold).All patients with SERM were postmenopausal and received daily 20–40 mg SERM. CumulativeSERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologicfeatures, such as International Federation of Gynecology and Obstetrics stage andoverall survival, were not significantly different between patients with S-uMMMT and NS-uMMMTor between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available forimmunostaining exhibited strong overexpression/null expression of p53 protein and significantlyincreased ERβ expression in carcinomatous and sarcomatous components.
Conclusions
SERMtherapy seemingly increases risk of S-uMMMT development; however, clinicopathologic featureswere similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expressionmight be involved in the etiology of S-uMMMT.

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Uterine carcinosarcomas: A case series of 9 cases from a low-income country
Boubacar Efared, Halidou Hamadou Koura, Aïchatou Balaraba Abani Bako, Idrissa Boubacar, Habiba Salifou Boureima, Garba Mahamadou, Hassan Nouhou
Medicine.2024; 103(40): e39773. CrossRef
Uterine carcinosarcoma: Unraveling the role of epithelial‐to‐mesenchymal transition in progression and therapeutic potential
Mohan Shankar Gopinatha Pillai, Pallab Shaw, Arpan Dey Bhowmik, Resham Bhattacharya, Geeta Rao, Shailendra Kumar Dhar Dwivedi
The FASEB Journal.2024;[Epub] CrossRef
Tamoxifen/toremifene

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Susanna Leskela, Belen Pérez-Mies, Juan Manuel Rosa-Rosa, Eva Cristobal, Michele Biscuola, María L. Palacios-Berraquero, SuFey Ong, Xavier Matias-Guiu Guia, José Palacios
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Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition: Haidy El-Azzamy, Andrea Balogh, Roberto Romero, Yi Xu, Christopher LaJeunesse, Olesya Plazyo, Zhonghui Xu, Theodore G. Price, Zhong Dong, Adi L. Tarca, Zoltan Papp, Sonia S. Hassan, Tinnakorn Chaiworapongsa, Chong Jai Kim, Nardhy Gomez-Lopez, Nandor Gabor Than; J Pathol Transl Med. 2017;51(3):264-283. Published online February 22, 2017; DOI: https://doi.org/10.4132/jptm.2016.12.20

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Abstract PDF Supplementary Material

Background
The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process.
Methods
Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples.
Results
The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found.
Conclusions
Our data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.

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American Journal of Obstetrics and Gynecology.2018; 219(5): 478.e1. CrossRef
Selective immuno-modulatory effect of prolactin upon pro-inflammatory response in human fetal membranes
Pilar Flores-Espinosa, Eduardo Preciado-Martínez, Araceli Mejía-Salvador, Gabriela Sedano-González, Luisa Bermejo-Martínez, Adalberto Parra-Covarruvias, Guadalupe Estrada-Gutiérrez, Rodrigo Vega-Sánchez, Isabel Méndez, Braulio Quesada-Reyna, Andrea Olmos-
Journal of Reproductive Immunology.2017; 123: 58. CrossRef

Case Report

Cystic Nephroma: A Case Report and Comparing Literature Review with Mixed Epithelial and Stromal Tumor of Kidney.: Hyun Jung Kim, Choong Hee Noh, Giyoung Kwon, Eunah Shin, Jung Yeon Kim, Kyeongmee Park; Korean J Pathol. 2011;45:S25-S28.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S25

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Abstract PDF: Cystic nephroma (CN) is a benign cystic neoplasm composed of mixed epithelial and stromal elements. Less than 200 cases have been reported. We had a patient, a 41-year-old woman, who had a huge typical CN. The patient was admitted for a right renal mass that was found incidentally. On laparaoscopic right nephrectomy, there was an encapsulated 7 cm multilocular cystic mass at the upper pole. Microscopically, the cystic wall was lined by a single layer of low cuboidal or hobnail epithelium without a solid area. The thin septa were composed of bland, ovarian type spindle cells. The main differential diagnoses were mixed epithelial and stromal tumor (MEST), low grade multilocular renal cell carcinoma, and tubulocystic carcinoma. The results of immunohistochemical staining were cytokeratin 7/19(+/+) and CD10(-) in lining epithelium, estrogen receptor/progesterone receptor(+/+) in stromal cells. After surgery, she was free of recurrence for 10 months. We report this rare case and compare it with other cystic renal tumors, especially MEST.

Original Articles

Pathologic Characteristics of Ovarian Hemorrhagic Polycyst in Estrogen Receptor-alpha (ERalpha) Knockout Mice and Roles of ERalpha in Hemorrhagic Polycyst.: Hyun Jin Son, Joo Heon Kim, Hye Kyung Lee, Mee Ja Park, Dong Wook Kang, Che Myong Ko; Korean J Pathol. 2010;44(4):376-383.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.376

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Abstract PDF: BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy causing anovulation in women of childbearing age. It has been well established that estrogen receptor-alpha knockout (ERalphaKO) mice display several pathologic ovarian phenotypes of PCOS. The aims of this study were to determine ovarian pathology in new ERalphaKO mice using a CreloxP approach and intra-ovarian ERalpha function as regulating key aspects of PCOS.
METHODS
ERalphaKO mice, which were deficient in exon 3 of the ERalpha gene, were used. Immunohistochemical studies were done on ovaries of control and ERalphaKO mice using antibodies specific to ERalpha, ERbeta, inhibin-alpha, and alpha-smooth muscle actin (SMA), as well as histochemical staining using Sudan black-B.
RESULTS
All ovaries of ERalphaKO mice were larger than control mouse ovaries and displayed a disrupted theca-interstitial tissue organization, multiple atretic follicles and multiple hemorrhagic cysts. None of the ERalphaKO mouse ovaries showed a corpus luteum. In addition, heavy deposition of Sudan black-B positive foamy cells was seen. The theca externa of preantral immature follicles and hemorrhagic cysts showed strong expression of alpha-SMA.
CONCLUSIONS
ERalphaKO mice show hemorrhagic polycystic ovaries and hyperplasia of the theca externa. This study demonstrates that the ERalpha is the functional key to the pathogenesis of PCOS.

An Immunohistochemical Study of the Relationships between Estrogen and Progesterone Receptors and Proliferating Cell Nuclear Antigen in Endometrial Hyperplasia and Adenocarcinoma.: Seol Mi Park, Hye Kyoung Yoon, Jong Eun Joo; Korean J Pathol. 1996;30(1):15-22.

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Abstract PDF: Estrogen and progesterone receptors exist in the epithelial and stromal cells of the endometrium. Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions of estrogen and progesterone in epithelial and stromal cells. This study was performed to evaluate the differences estrogen and progesterone receptor(ER/PR) expression in the epithelial and stromal cells of endometrial hyperplasias and adenocarcinomas using immunohistochemical methods. Immunohistochemical analysis of proliferating cell nuclear antigen(PCNA) was done to evaluate a possible correlation between PCNA and hormone receptor expression. Evaluation was based on samples from 31 simple hyperplasias, 30 complex hyperplasias, and 32 adenocarcinomas. The immunohistochemical expression of ER, PR and PCNA in epithelial and stromal cells were examined according to a scoring system based on the percentage of positive cells and the staining intensity. The results were as follows; 1) The expression of ER and PR in epithelial cells showed a graded, significant decreases in simple hyperplasia, complex hyperplasia and endometrial carcinoma, in that order(ER: P=0.008, PR: P= 0.026). 2) PR expression in the stromal cells showed a significant decrease between hyperplasia and adenocarcinoma(P=0.003). The difference in ER expression was not significant. 3) In stromal cells, the decrease in PR expression was more prominent than the decrease in ER expression when complex hyperplasia was compared to simple hyperplasia. 4) The PCNA expression in simple and complex hyperplasia and adenocarcinoma was not higher than the expression of PCNA in nomal proliferative endometrium. There was no significant difference in PCNA expression between simple and complex hyperplasia and adenocarcinoma(P=0.073). 5) A negative correlation between PCNA and ER/PR expression was not demonstrated in simple and complex hyperplasia, or in adenocarcinoma. Endometrial hyperplasia and adenocarcinoma are probably related to a paracrine action of estrogen and progesterone in epithelial and stromal cells. A progressive loss of PR expression in stromal cells may induce abnormal proliferation of endometrium due to a disrupted hormonal balance.

Clinical Value of Demonstration of Estrogen and Progesterone Receptors using Paraffin Wax Sections in Breast Carcinoma.: Hye Kyung Ahn, Yun Jung Kim, Young Euy Park; Korean J Pathol. 1996;30(2):89-93.

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Abstract PDF: This study aimed at assessing the usefulness of paraffin wax sections for demonstration of ER(estrogen receptor) and PR(progesterone receptor), using brief microwave processing rather than proteolytic predigestion. The receptor status of a breast cancer is often into consideration when planning treatment nowadays. As biochemical receptor assays require large amount of fresh tumor tissue and are not always available for all tumors, pathologists are now increasingly asked to provide a service for the assessment of the receptor status in tissue routine sections. Until recently, immunohistochemical demonstration of receptors was used in frozen sections. Therefore, routinely processed paraffin wax sections of 25 cases of breast carcinoma with known ER and PR concentrations, estimated by the standard DCC(dextran-coated charcoal) biochemical assay, were examined using the ABC immunoperoxidase technique. The results were assessed semiquantitably, using a five grade scoring system. Of the 25 cases examined, with DCC cutoff point being <10 fmol,71% and 75% in positivity of each ER, PR receptor is concordant. Statistic analysis demonstrates high relationship between scoring system of IH method and DCC value in ER (R=0.6061, p=0.001) and PR (R=0.5832, p=0.001). The IH method can provide easily assessed reliable positive information about ER, PR status of breast carcinoma using routinely processed paraffin wax sections.

Immunohistochemical Analysis of Estrogen Receptors and Progesterone Receptors in Leiomyoma of Uterus Compared with PCNA Index.: Jung Ran Kim; Korean J Pathol. 1996;30(2):140-149.

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Abstract PDF: Estrogen receptor(ER) and progesterone receptor(PR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in leiomyomas and myometrium from same patients from 38 women in various stages of the menstrual cycle, menopause and pregnancy. Two postpartum uteri are also included. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution, and the results were compared with those of PCNA index. In all samples, ER and PR localized within the nuclei of target cells. The histochemical score of ER in leiomyoma was significantly greater than that found in myometrium. But ER in leiomyoma was expressed in cyclic fashion(r=0.45, P=0.006), like as in myometrium, throughout the menstrual cycle, paralleled by a concomitant, though delayed. In contrast, PR content constantly maintained in myometrium and leiomyoma throughout menstrual cycle, and there was no significant difference between them. However, leiomyoma and myometrium of pregnancy showed a significant reduction in the amount of ER and PR localized. PCNA index in leiomyoma(14.9+/-24.4) was also significantly higher than that found in myometrium(2.1+/-3.3). The index declined throughout the secretory phase. The leiomyoma had increased PCNA index during pregnancy, while the increasing rate in leiomyoma was lower than that of myometrium. The growth potential of leiomyomas is appearently higher than that of myometrium under the high progesterone level. The most of neoplasm with high PCNA index(10 above) contained absolute or relative abundant PR or ER content. Alteration of receptor content may be an important mechanism in steroid dependent growth of leiomyoma and may provide information useful in the clinical management of this neoplastic disorder.

Analysis of Estrogen and Progesterone Receptors in Breast Carcinoma: Comparison of immunocytochemical assay with biochemical dextran-coated charcoal assay.: Ill Hyang Ko, Kyeong Mee Park; Korean J Pathol. 1996;30(3):228-237.

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Abstract PDF: Estrogen receptor(ER) is a soluble form of hormone receptor protein which is located in the nucleus and cytoplasm of a cell is found in 60% of cases of the cells of breast carcinoma. Fifty to sixty percent of ER positive breast carcinoma responds to antihormone therapy wheres the response rate is only 5% in ER negative tumors. Currently, the ER assay has become a standard index in the management and prediction of the prognosis of advanced breast carcinoma. Semiquantitative biochemical assay, dextran-coated charcol(DCC) assay, to measure ER from fresh tissue was first developed by Korenman in 1970 using isotope-labled ertradiol, has been widely utilized. In 1978, Kurzon newly developed immunocytochemical assay(ICA) employing monoclonal antibody against those hormone receptors to detect intracellular localization of ER and progesterone receptor (PR). The results of the assay have been reported by many investigators thereafter. The purpose of this study was to evaluate the hormonal receptors with a monoclonal antibody using an immunoperoxidase procedure to detect both estrogen and progesterone receptors (ER-immunocytochemical assay:ER-ICA and PR-immunocytochemical assay:PR-ICA) in 59 cases of paraffin embedded sections from formalin-fixed and routinely processed breast carcinoma tissue. Concomitantly, fine-needle aspiration biopsy cytology of the breast cancer from 29 women were assayed for ER/PR receptors. Results were compared with quantitative biochemical values determined from dextran-coated charcoal(DCC) assay on the fresh tumor tissue obtained subsequently from the surgery. ER-ICA showed positive result in 22 out of 36 DCC-positive cases(sensitivity, 61.1%) and negative in 23 out of 23 DCC-negative cases (specificity, 100.0%). PR-ICA was positive in 33 out of 35 DCC-positive cases(sensitivity, 94.3%) and negative in 16 out of 24 DCC-negative cases(specificity, 66.7%). The value of ER-ICA or PR-ICA positivity were roughly correlated with the concentration of ER/PR receptors analyzed by DCC method. The results of both methods were correlated with the nuclear grade of the tumor(ICA:p=0.002, DCC: p=0.015) but were not correlated with histologic grade(ICA: p=0.323, DCC: p=0.0164). ER-ICA positivity was correlated with lower incidence of axillary node metastasis (p=0.021) but no significant correlation between PR-ICA positivity and node metastasis(p=0.171). Both ER/PR-ICA positivity were not correlated with age(p=0.924) and tumor size(p=0.663). The score of ICA particularly ER was proportional to DCC level(ER: r=0.5, p=0.000, PR: r=0.2, p=0.000). ICA concordance with DCC of ER and PR were 76.3% and 83.1%, respectively. The concordance of PR-ICA and DCC was proportional but was statistically less significant. In aspiration biopsy cytology the concordance of ER/PR-ICA and DCC were 72.4% and 65.5%, respectively. Immunocytochemical staining to identify ER/PR receptors from the tissue of breast carcinoma would be tested as a mean to substitute for the conventional DCC method.

Expression of p53, bcl-2 Proteins and Estrogen Receptors in Human Breast Cancer.: Hee Kyung Chang, Choong Han Lee, Man Ha Huh; Korean J Pathol. 1996;30(8):662-670.

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Abstract PDF: In 56 breast cancer tissues (infiltrating ductal carcinoma) with a clinical follow-up period of more than 5 years, positivity of estrogen receptor(ER) by enzyme immunoassay and expressions of bcl-2 and p53 oncoproteins by immunohistochemistry were evaluated. The purposes of this study were to determine prevalence of bcl-2 and p53 in breast cancer, the interrelationship between expression of the proteins and estrogen receptor, correlation between histologic grade and the expression of the tumor-related oncogenes, and to explore the biologic bahavior of breast cancer (lymph node metastasis, recurrence rate, and survival) via expression of bcl-2 and p53. Twelve of 56 (21.4%) carcinomas were bcl-2 positive, and seventeen (30.4%) were p53- positive. Eleven of 12 bcl-2 positive tumors (91.7%) were ER-positive, and bcl-2 expression was significantly associated with ER-positivity(P=0.043). Seven of 36 ER-positive tumors (12.5%) were p53 positive, and p53 expression was inversely associated with ER-positivity(P=0.006) significantly. The bcl-2 protein expression showed a significant relationship to low histologic grade of tumor (P=0.0002), and an almost significant relationship to lower recurrence rate (P=0.09). The p53 protein expression showed a significant relationship to high histologic grade of tumor (P=0.002) and an almost significant relationship to lymph node metastasis (P=0.09). Also an almost inverse relationship between bcl-2 and p53 was demonstrated (P=0.057). The bcl-2 expression had a tendency to be associated with longer patient survival(P= 0.09), but p53 immunoreaction was found not to be associated with shorter patient survival(P=0.16). These results provide further evidence that higher incidence of bcl-2 expression is correlated with higher incidence of ER and lower grade of tumor, while p53 expression is correlated with lower incidence of ER and higher grade of tumor. In conclusion, although the biologic function of bcl-2 protein is not yet well understood in breast cancer, our results suggest that bcl-2 and p53 oncoproteins might play significant roles in estrogen receptor and development of breast cancer. But their prognostic significance could not be determined; our results are 'not significant' but 'almost significant'. Thus, contribution of bcl-2 and p53 immunohistochemical phenotyping of breast cancer with ER to the clinical management need verification in larger series.

Histopathologic Findings & Expression of bcl-2 of the Endometrium Analysis of 1,000 consecutive biopsies of uterine bleeding .: Hye Kyung Lee, Dong Geun Lee, Ho Lee, Sang In Shim; Korean J Pathol. 1998;32(3):208-214.

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Abstract PDF: We evaluated 1,000 consecutive endometrial curettage samples obtained over a 30 month period. The clinico-pathologic correlation was analysed according to Hendrickson's five criteria based on the practical view. The causes of uterine bleeding in decreasing order of occurrence were as follows: 1) hormonal imbalance lesions (49.2%) encompassing glandular and stromal breakdown suggesting anovulatory bleeding, proliferative phase endometrium, and disordered proliferative endometrium, 2) pregnancy associated lesions (24.2%), 3) organic lesions (13.5%), 4) endometrial hyperplasia (6.9%), and 5) inadequate specimen (6.2%). According to age, pregnancy related lesions were most frequent in the third decade. In the fourth, fifth, and sixth decades, hormonal imbalance lesions were the most common cause. In approximately 30% of the samples, there were two or three morphologic patterns such as anovulatory bleeding with an endometrial polyp, postabortal bleeding with inflammation, and glandular-stromal dissociation with a polyp, which suggested there was a variable histologic morphology in the same disease spectrum. Using immunohistochemical techniques we studied the hormonal dependency of bcl-2 oncoprotein in anovulatory bleeding, endometrial hyperplasia, and proliferative endometrium. 70% of anovulatory bleeding specimens showed weak positivity in the epithelial cytoplasm, and all cases of endometrial hyperplasia and carcinoma showed a strong positivity. These results suggest that there is a estrogenic hormonal dependency of apoptosis in the endometrium.

Cyclin D1 Expression in 101 Cases of Breast Carcinoma.: Duck Hwan Kim, Eun Sook Nam, Hyung Sik Shin, Jin Woo Ryu, Jai Hyang Go, Young Lyun Oh, Sang Yong Song, Dae Shick Kim, Min Chul Lee; Korean J Pathol. 1998;32(4):266-272.

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Abstract PDF: Cyclin D1, a cell cycle regulator essential for G1 phase progression, is a candidate proto-oncogene implicated in pathogenesis of several human carcinomas including breast carcinoma. We studied the cyclin D1 expression in 101 cases of primary breast carcinoma tissues. The overexpression of cyclin D1 was immunohistochemically demonstrated in 34 (37.8%) of 90 cases of invasive breast carcinoma. Positive cyclin D1 staining was seen in 32 of 79 invasive ductal carcinomas, and 2 of 3 mucinous carcinomas. All 5 medullary carcinomas, 2 invasive lobular carcinomas, and 1 metaplastic carcinoma were negative. Cyclin D1 overexpression was observed in 9 of 11 ductal carcinoma in situ (DCIS). Normal epithelial components, either ductal or lobular, were not immunoreactive for cyclin D1. No significant correlations were observed between cyclin D1 immunoreactivity and other parameters including tumor size, clinical stage, nuclear or histologic grades, lymphatic or angioinvasion, lymph node metastasis, and immunohistochemical status of progesterone receptor, p53 and c-erbB-2. The overexpression of cyclin D1 was positively correlated with estrogen receptor status (p=0.025). Based on our results, the cyclin D1 protein aberration may play a role in tumorigenesis of breast carcinoma, but does not seem to have prognostic value in invasive breast carcinoma without hormonal treatment.

Immunohistochemical Expression of p53 Protein, Estrogen and Progesterone Receptor in Soft Tissue Leiomyosarcoma and Its Significance.: Byung Heon Kim; Korean J Pathol. 1998;32(11):1015-1024.

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Abstract: This study was carried out to evaluate the expressions of the p53 protein, the estrogen receptor (ER) and the progesterone receptor (PR), as well as the relationship between their expressions and clinicopathologic prognostic factors with storage duration of a paraffin block, and correlation between the p53 protein, the ER and the PR expressions in 29 cases of leiomyosarcoma of soft tissue. The expressions of the p53 protein, the ER and the PR were semiquantiatively analyzed in paraffin sections by the immunohistochemical method out of 29 cases the p53 protein, ER and PR were expressed in 9 (31.0%), 2 (6.9%) and 5 (17.2%), respectively. The expression of the p53 protein was not significantly associated with sex, age, anatomic site, tumor size, tumor depth, histological differentiation or mitotic rate (p>0.05), but statistically correlated to storage duration of a paraffin block (p=0.028). There was no significant relationship between the expression of the ER and all the clinocopathological prognostic factors with storage duration of a paraffin block (p>0.05). The expression of the PR was related to the histological differentiation (p=0.02), but not related to other clinicopathological prognostic parameters and storage duration of a paraffin block (p>0.05). The expression of the p53 protein and the PR had a significant relationship (p=0.022), but the expression of the p53 protein and the ER had no significant correlation. In conclusion, these results suggest that the expression of the p53 protein and the PR may play a role in development and growth of soft tissue leiomyosarcoma. Further studies of large numbers are needed to clarify the exact relationship between tumorigenesis and the p53 and the PR expressions in leiomyosarcoma of soft tissue.

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