Journal of Pathology and Translational Medicine

Original Articles

Mismatch repair deficiency and clinicopathological characteristics in endometrial carcinoma: a systematic review and meta-analysis: Alaa Salah Jumaah, Hawraa Sahib Al-Haddad, Mais Muhammed Salem, Katherine Ann McAllister, Akeel Abed Yasseen; J Pathol Transl Med. 2021;55(3):202-211. Published online April 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.02.19

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Background
Loss of mismatch repair (MMR) occurs frequently in endometrial carcinoma (EC) and is an important prognostic marker. However, the frequency of MMR deficiency (D-MMR) in EC remains inconclusive. This systematic review and meta-analysis addressed this inconsistency and evaluated related clinicopathology.
Methods
Electronic databases were searched for articles: PubMed, Science Direct, Web of Science, EMBASE, and the Wiley Online Library. Data were extracted from 25 EC studies of D-MMR to generate a clinical dataset of 7,459 patients. A random-effects model produced pooled estimates of D-MMR EC frequency with 95% confidence interval (CI) for meta-analysis.
Results
The overall pooled proportion of D-MMR was 24.477% (95% CI, 21.022 to 28.106) in EC. The Lynch syndrome subgroup had 22.907% pooled D-MMR (95% CI, 14.852 to 32.116). D-MMR was highest in type I EC (25.810) (95% CI, 22.503 to 29.261) compared to type II (13.736) (95% CI, 8.392 to 20.144). Pooled D-MMR was highest at EC stage and grades I–II (79.430% and 65.718%, respectively) and lowest in stages III–IV and grade III (20.168% and 21.529%). The pooled odd ratios comparing D-MMR to proficient MMR favored low-stage EC disease (1.565; 0.894 to 2.740), lymphovascular invasion (1.765; 1.293 to 2.409), and myometrial invasion >50% (1.271; 0.871 to 1.853).
Conclusions
Almost one-quarter of EC patients present with D-MMR tumors. The majority has less aggressive endometrioid histology. D-MMR presents at lower tumor stages compared to MMR-proficient cases in EC. However other metastatic parameters are comparatively higher in the D-MMR disease setting.

Citations

Citations to this article as recorded by

Guidelines of the Brazilian Society of Surgical Oncology for anatomopathological, immunohistochemical, and molecular testing in female tumors
Reitan Ribeiro, Filomena Marino Carvalho, Glauco Baiocchi, Rodrigo Santa Cruz Guindalini, Juliano Rodrigues da Cunha, Carlos Henrique dos Anjos, Caroline de Nadai Costa, Ana Carolina Leite Vieira Costa Gifoni, Renato Cagnacci Neto, Allyne Queiroz Carneiro
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Microsatellite instability as a reliable marker of coexisting endometrial cancer in atypical endometrial hyperplasia
А. E. Protasova, G. A. Raskin, M. S. Sobivchak
Tumors of female reproductive system.2024; 20(2): 105. CrossRef
Prevalence of Mismatch Repair Gene Defects by Means of Immuno-histochemistry Staining for MMR Proteins in Endometrial Cancer
Kaustubh Girish Burde, Indu R. Nair, Pavithran Keechilattu, Anupama Rajanbabu
The Journal of Obstetrics and Gynecology of India.2024;[Epub] CrossRef
Refining of cancer-specific genes in microsatellite-unstable colon and endometrial cancers using modified partial least square discriminant analysis
Woong Na, Sung Hak Lee, Seunghee Lee, Jong-Seok Kim, Seung Yun Han, Yong Min Kim, Mihye Kwon, Young Soo Song
Medicine.2024; 103(52): e41134. CrossRef
Cancer-specific functional profiling in microsatellite-unstable (MSI) colon and endometrial cancers using combined differentially expressed genes and biclustering analysis
Woong Na, Il Ju Lee, Insong Koh, Mihye Kwon, Young Soo Song, Sung Hak Lee
Medicine.2023; 102(19): e33647. CrossRef
Clinicopathological characteristics of endometrial carcinomas according to DNA mismatch repair protein status
Daniela de Freitas, Fernando Nalesso Aguiar, Cristina Anton, Danielle Cristina de Almeida, Carlos Eduardo Bacchi, Jesus Paula Carvalho, Filomena Marino Carvalho
Heliyon.2023; 9(6): e17495. CrossRef
Mesonephric-like Adenocarcinoma of the Uterine Corpus: Genomic and Immunohistochemical Profiling with Comprehensive Clinicopathological Analysis of 17 Consecutive Cases from a Single Institution
Hyun-Hee Koh, Eunhyang Park, Hyun-Soo Kim
Biomedicines.2023; 11(8): 2269. CrossRef
miR-486-3p Controls the Apoptosis of Endometrial Carcinoma Cells
Donghua Wang, Xiaoli Liu, Lirong Cao, Shixiong Gong, Yi He, Xiangbin Jiang, Zhongxian Wang
Journal of Biomaterials and Tissue Engineering.2022; 12(5): 1002. CrossRef
The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review
Amelia Favier, Justine Varinot, Catherine Uzan, Alex Duval, Isabelle Brocheriou, Geoffroy Canlorbe
Cancers.2022; 14(15): 3783. CrossRef

Interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma: Ho Jin Jung, Soo Yeon Lee, Jin Hwa Hong, Yi Kyeong Chun; J Pathol Transl Med. 2021;55(1):43-52. Published online December 3, 2020; DOI: https://doi.org/10.4132/jptm.2020.10.04

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Abstract PDF

Background
The accurate pathologic diagnosis and subtyping of high-grade endometrial carcinoma are often problematic, due to its atypical and overlapping histopathological features.
Methods
Three pathologists reviewed 21 surgically resected cases of advancedstage endometrial carcinoma. The primary diagnosis was based only on hematoxylin and eosin stained slides. When a discrepancy arose, a secondary diagnosis was made by additional review of immunohistochemical (IHC) stains. Finally, three pathologists discussed all cases and rendered a consensus diagnosis.
Results
The primary diagnoses were identical in 13/21 cases (62%). The secondary diagnosis based on the addition of IHC results was concordant in four of eight discrepant cases. Among four cases with discrepancies occurring in this step, two cases subsequently reached a consensus diagnosis after a thorough discussion between three reviewers. Next-generation sequencing (NGS) study was performed in two cases in which it was difficult to distinguish between serous carcinoma and endometrioid carcinoma. Based on the sequencing results, a final diagnosis of serous carcinoma was rendered. The overall kappa for concordance between the original and consensus diagnosis was 0.566 (moderate agreement).
Conclusions
We investigated stepwise changes in interobserver diagnostic reproducibility in advanced-stage endometrial carcinoma. We demonstrated the utility of IHC and NGS study results in the histopathological diagnosis of advanced-stage endometrial carcinoma.

Citations

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Accuracy of endometrial sampling in the diagnosis of endometrial cancer: a multicenter retrospective analysis of the JAGO-NOGGO
Zaher Alwafai, Maximilian Heinz Beck, Sepideh Fazeli, Kathleen Gürtler, Christine Kunz, Juliane Singhartinger, Dominika Trojnarska, Dario Zocholl, David Johannes Krankenberg, Jens-Uwe Blohmer, Jalid Sehouli, Klaus Pietzner
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Application of NGS molecular classification in the diagnosis of endometrial carcinoma: A supplement to traditional pathological diagnosis
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Cancer Medicine.2023; 12(5): 5409. CrossRef
Risk Stratification of Endometrial Cancer Patients: FIGO Stage, Biomarkers and Molecular Classification
Jenneke C. Kasius, Johanna M. A. Pijnenborg, Kristina Lindemann, David Forsse, Judith van Zwol, Gunnar B. Kristensen, Camilla Krakstad, Henrica M. J. Werner, Frédéric Amant
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The frequency of POLE-mutation in endometrial carcinoma and prognostic implications: a systemic review and meta-analysis: Alaa Salah Jumaah, Mais Muhammed Salim, Hawraa Sahib Al-Haddad, Katherine Ann McAllister, Akeel Abed Yasseen; J Pathol Transl Med. 2020;54(6):471-479. Published online September 2, 2020; DOI: https://doi.org/10.4132/jptm.2020.07.23

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Abstract PDF Supplementary Material

Background
Endometrial carcinoma (EC) is classified into four distinct molecular subgroups including ultramutated DNA polymerase epsilon (POLE). POLE-mutated tumors have the best prognosis and are a promising target for immunotherapy. This meta-analysis consolidated the reported variation of POLE-mutant frequency and assessed prognostic value in EC.
Methods
Internet searches explored scientific data bases: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials databases. Data was extracted from eligible studies including: sample size, number of positive POLE-mutant cases, sequencing information, clinicopathologic data, and survival data. Meta-analysis and a random-effects model produced pooled estimates of POLE frequency and prognostic parameters using 95% confidence intervals (CI), hazard ratios (HR), and odd ratios (OR).
Results
Six thousand three hundred and forty-six EC patient cases were pooled from 25 studies. The pooled proportion of POLE gene mutation in EC was 8.59% (95% CI, 7.01 to 10.32), of which 8.22% (95% CI, 6.27 to 10.42) were type I and 0.93% (95% CI, 0.34 to 1.81) type 2. Clinicopathologic data showed that POLE-mutated tumors are mostly endometrioid. They present at higher levels in earlier stages (I–II) of EC (89.51%; 95% CI, 81.11 to 95.66) at the highest grade III (51.53%; 95% CI, 36.08 to 66.84) with reduced myometrial invasion (OR, 1.48, 95% CI, 0.99 to 2.20). Survival analysis indicated favorable overall survival (HR, 0.90), disease-specific survival (HR, 0.41), and progression-free survival (HR, 0.23) for POLE mutant EC.
Conclusions
Almost one-tenth of EC patients have POLE-mutated tumors. Given their improved prognostic potential, identifying the POLE mutation status is key for the management of EC patients.

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Mismatch repair deficiency and clinicopathological characteristics in endometrial carcinoma: a systematic review and meta-analysis
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High Expression of Galectin-1, VEGF and Increased Microvessel Density Are Associated with MELF Pattern in Stage I-III Endometrioid Endometrial Adenocarcinoma: Dmitry Aleksandrovich Zinovkin, Sergey Leonidovich Achinovich, Mikhail Grigoryevich Zubritskiy, Jacqueline Linda Whatmore, Md Zahidul Islam Pranjol; J Pathol Transl Med. 2019;53(5):280-288. Published online June 27, 2019; DOI: https://doi.org/10.4132/jptm.2019.05.13

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Abstract PDF

Background
In this study, we investigate the expression of markers of angiogenesis and microvessel density (MVD) in cases of microcystic, elongated and fragmented (MELF) pattern, with its prognostic role in the survival of endometrioid endometrial adenocarcinomas (EA) patients.
Methods
In this study, 100 cases of EA, 49 cases with MELF pattern and 51 without, were immunohistochemically stained for galectin-1, vascular endothelial growth factor (VEGF), and MVD. Morphometry and statistical (univariate and multivariate) analyses were performed to assess overall survival (OS) and disease-free survival.
Results
The expression of VEGF (p<.001) and galectin-1 (p<.001), as well as MVD area (p<.001) and number of vessels/mm2 (p<.050), were significantly higher in the +MELF pattern group compared to the –MELF group. A low negative correlation between MELFpattern and the number of days of survival (p<.001, r=–0.47) was also found. A low positive correlation of MELF-pattern with galectin-1 expression (p<.001, r=0.39), area of vessels/mm2 (p<.001, r=0.36), outcome of EA (p<.001, r=0.42) and VEGF expression (p<.001, r=0.39) suggests potential pathological relevance of these factors in the prognosis of EA. A univariate survival analysis indicated a role for all parameters of survival. Multivariate Cox proportional hazard regression analysis revealed that only area of vessels/mm2 (hazard ratio [HR], 1.018; 95% confidence interval [CI], 1.002 to 1.033), galectin-1 (HR, 1.049; 95% CI, 1.025 to 1.074) and VEGF (HR, 1.049; 95% CI, 1.022 to 1.077) play key roles in OS.
Conclusions
This study reports an increase in MVD, VEGF and galectin-1 expression in EA with MELF pattern and suggests that MELF pattern, along with the angiogenic profile, may be a prognostic factor in EA.

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Association of Local and Distant Organ Metastases With MELF Pattern in Endometrial Cancer
Varol Gülseren, Ertuğrul Şen, Mehmet Dolanbay, Fulya Çağli, Nahit Topaloğlu, Figen Öztürk, Bülent Özçelik, Serdar Serin, Kemal Güngördük
International Journal of Gynecological Pathology.2024;[Epub] CrossRef
Tumour budding, MELF-pattern and tumour-infiltrating lymphocytes as possible pathomorphological parameters of the course of endometrioid adenocarcinoma of the uterine corpus
D. A. Zinovkin, I. V. Veyalkin, S. L. Achinovich, I. I. Slepokurova, Yu. A. Lyzikova, A. Farooq
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Emilie Alard, Aura-Bianca Butnariu, Marta Grillo, Charlotte Kirkham, Dmitry Aleksandrovich Zinovkin, Louise Newnham, Jenna Macciochi, Md Zahidul Islam Pranjol
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Potential Role for a Panel of Immunohistochemical Markers in the Management of Endometrial Carcinoma: Amany Salama, Mohammad Arafa, Eman ElZahaf, Abdelhadi Mohamed Shebl, Azmy Abd El-Hameed Awad, Sylvia A. Ashamallah, Reda Hemida, Anas Gamal, Abd AlRahman Foda, Khaled Zalata, El-Said M. Abdel-Hady; J Pathol Transl Med. 2019;53(3):164-172. Published online February 28, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.12

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Abstract PDF

Background
In order to improve the efficacy of endometrial carcinoma (EC) treatment, identifying prognostic factors for high risk patients is a high research priority. This study aimed to assess the relationships among the expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and the different histopathological prognostic parameters in EC and to assess the value of these in the management of EC.
Methods
We examined 109 cases of EC. Immunohistochemistry for ER, PR, HER2, and Ki-67 were evaluated in relation to age, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and grade, depth of infiltration, cervical and ovarian involvement, lymphovascular space invasion (LVSI), and lymph node (LN) metastasis.
Results
The mean age of patients in this study was 59.8 ± 8.2 years. Low ER and PR expression scores and high Ki-67 expression showed highly significant associations with non-endometrioid histology (p = .007, p < .001, and p < .001, respectively) and poor differentiation (p = .007, p < .001, and p <. 001, respectively). Low PR score showed a significant association with advanced stage (p = .009). Low ER score was highly associated with LVSI (p = .006), and low PR scores were associated significantly with LN metastasis (p = .026). HER2 expression was significantly related to advanced stages (p = .04), increased depth of infiltration (p = .02), LVSI (p = .017), ovarian involvement (p = .038), and LN metastasis (p = .038). There was a close relationship between HER2 expression and uterine cervical involvement (p = .009). Higher Ki-67 values were associated with LN involvement (p = .012).
Conclusions
The over-expression of HER2 and Ki-67 and low expression of ER and PR indicate a more malignant EC behavior. An immunohistochemical panel for the identification of high risk tumors can contribute significantly to prognostic assessments.

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Immunohistochemical Expression of Oestrogen and Epidermal Growth Factor Receptors in Endometrial Cancerous in Sudanese Patients
Salwa Abdalraheem Abubaker, Mohamed Elfatih Abdelwadoud, Mutaz Mohamed Ali, Hadia Alhaj Ahmad, Abuobieda Mohamed Khlafalla, Osman Mohammed Elmahi, Hisham Ali Waggiallah
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Expression of ER/PR Receptor, Her-2/neu, Ki67 and p53 in Endometrial Carcinoma: Clinicopathological Implication and Prognostic Value
V. B. Shivkumar, Manisha A. Atram, Nitin M. Gangane
Indian Journal of Gynecologic Oncology.2020;[Epub] CrossRef
Immunohistochemical study of ER, PR, p53 and Ki67 expression in patients with endometrial adenocarcinoma and atypical endometrial hyperplasia
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Investigation of the Roles of Cyclooxygenase-2 and Galectin-3 Expression in the Pathogenesis of Premenopausal Endometrial Polyps: Esin Kasap, Serap Karaarslan, Esra Bahar Gur, Mine Genc, Nur Sahin, Serkan Güclü; J Pathol Transl Med. 2016;50(3):225-230. Published online April 16, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.08

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Abstract PDF

Background
The pathogenesis and etiology of endometrial polyps has not been elucidated. In this study, we aimed to examine the pathogenic mechanisms of endometrial polyp development using immunohistochemistry. We evaluated the expression of galectin-3 and cyclooxgenase-2 (COX-2) during the menstrual cycle in premenopausal women with endometrial polyps or normal endometrium.
Methods
Thirty-one patients with endometrial polyps and 50 healthy control patients were included in this study. The levels of expression of COX-2 and galectin-3 were studied by immunohistochemistry.
Results
The percentage of COX-2–positive cells and the intensity of COX-2 staining in the endometrium did not vary during the menstrual cycle either in the control group or in patients with endometrial polyps. However, expression of galectin-3 was significantly lower in endometrial polyps and during the proliferative phase of the endometrium compared with the secretory phase.
Conclusions
Our data suggests that the pathogenesis of endometrial polyps does not involve expression of COX-2 or galectin-3.

Citations

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ER and COX2 expression in endometrial hyperplasia processes
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Medicine.2023; 102(33): e34864. CrossRef
Novel microarchitecture of human endometrial glands: implications in endometrial regeneration and pathologies
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Brief Case Report

The Limitations of Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology in the Diagnosis of Pancreatic Serous Cystadenoma: A Brief Case Report: Heae Surng Park, Sun Och Yoon, Beom Jin Lim, Joo Hee Kim, Soon Won Hong; Korean J Pathol. 2014;48(5):405-408. Published online October 27, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.405

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Original Articles

Diagnostic Utility of the JAZF1/JJAZ1 Gene Fusion in Endometrial Stromal Sarcomas and Their Histologic Variants.: Sang Ryung Lee, Joon Seon Song, Ga Hye Kim, Jene Choi, Hyung Kyoung Kim, Yonghee Lee, Kyu Rae Kim; Korean J Pathol. 2011;45(5):498-505.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.498

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Abstract PDF: BACKGROUND
The diagnosis of endometrial stromal sarcoma (ESS) is often difficult in cases showing diverse histological differentiation or in undifferentiated endometrial sarcoma (UES). Recently, JAZF1/JJAZ1 gene fusion has been described as a defining feature of low-grade ESS (LGESS). However, its prevalence is variably reported, and the diagnostic utility has rarely been examined for cases showing various histological differentiation.
METHODS
To test the diagnostic utility of JAZF1/JJAZ1 gene fusion in difficult cases, we compared the prevalence of the JAZF1/JJAZ1 fusion gene in LGESS with and without histological differentiation.
RESULTS
The JAZF1/JJAZ1 fusion transcript was detected in 18 of 21 LGESS (85.7%), including 14 classical LGESS (93%), four LGESS with diverse histological differentiation (67%), and two with UES (28.6%). Positive cases included two LGESS with sex cord-like differentiation, one with osseous differentiation, and two UES. LGESS showing smooth muscle differentiation revealed the fusion transcript only in the classic area. Direct sequencing analysis of two LGESS revealed a previously reported breakpoint at t(7;17)(p15;q21).
CONCLUSIONS
The JAZF1/JJAZ1 fusion gene was identified in a significant proportion of LGESS showing secondary histological differentiation except in cases with smooth muscle differentiation. Thus, this fusion gene may be useful to confirm the diagnosis in difficult cases of LGESS.

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.

A Study of Bcl-2 Oncoprotein Expression in Endometrial Carcinoma Correlated with Hormone Receptor Status.: Young Im Han, Hye Jin Lee, Ji Yeon Lee, Sun Kyung Lee; Korean J Pathol. 1996;30(5):408-416.

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Abstract PDF: Bcl-2 is a proto-oncogene initially described in follicular lymphoma, associated with chromosomal translocation(14;18). Recent studies have shown the presence of Bcl-2 in nonhematolymphoid tissue, especially in hormonally responsive tissue. The endometrium is an attractive model for studying the hormone dependent regulation of Bcl-2 expression. We have studied the immunoreactivity of Bcl-2 oncoprotein in relation to the immunoreactivity of estrogen receptors(ER) and progesterone receptors(PR) by immunohistochemistry in 52 human endometrial carcinomas, according to nuclear grade. The results obtained are summarized as followings, 1) Immunohistochemical grade of Bcl-2 showed a significant inverse correlation with nuclear grade. 2) Immunohistochemical grades of ER and PR also showed a significant inverse correlation with nuclear grade, and were well correlated with each other. 3) Immunohistochemical grades of Bcl-2 and hormone receptors showed a strongly significant correlation. On the basis of the above results, we suggest that Bcl-2 expression may be under hormone dependent control and that it can be used in prognosis and choice of hormonal therapy in the presence of hormone receptor.

Effects of Progesterone Treatment on the Squamous or Morular Metaplasia Associated with Endometrial Hyperplasia.: Kyu Rae Kim, Hee Jeong Ahn; Korean J Pathol. 1996;30(8):680-686.

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Abstract PDF: During evaluation of follow-up curettage of endometrial hyperplasia after progesterone treatment, we have noticed that the foci of squamous or morular metaplasia are persistent or even markedly increased after the hyperplastic glands have all disappeared. These observations have led us to study the histological changes of squamous or morular metaplasia in the hyperplastic endometrium after progesterone treatment and to examine the changes of estrogen receptors(ER) and progesterone receptors(PR) to find out, if there is any pathogenetic role of progesterone administration on the squamous or morular metaplasia. Squamous or morular metaplasia was associated in 21 cases (13.5 %) out of 156 endometrial hyperplasia during the study periods and all of them were associated with complex hyperplasia, but not associated with simple hyperplasia. At follow-up curettage after progesterone treatment, squamous metaplasia newly appeared in 3 cases(20 %), markedly increased in 4 cases(26.7%), persisted in 4 cases(26.7%) and decreased in 4 cases(26.7%), even after hyperplastic glands have all disappeared or were markedly decreased. On immunohistochemical staining, metaplastic foci showed ER- and PR- in 13 cases (87 %) in contrast to the surrounding endometrium and the remaining 2 cases showed minimal ER+ and PR+ confined to several nuclei. Intensity or staining pattern of ER and PR in metaplastic foci were not changed with progesterone treatment. In the background endometrium, intensity of glandular ER+ and PR + was higher than that of the stroma at the initial curettage, however, progesterone treatment predominantly down-regulated glandular ER+ more than stromal ER+. Increment or persistence of squamous metaplasia along the progesterone treatment seemingly would implicate hormonal influences as playing a significant role in the formation of squamous or morular metaplasia and the absence of cellular receptors for these hormones in the metaplastic foci may suggest qualitative changes in the receptors.

Overexpression of p53 Protein in Endometrial Hyperplasia and Adenocarcinoma.: Yun Sin Kim, Mi Sook Lee, Sung Chul Lim, Jang Shin Sohn, Chae Hong Suh; Korean J Pathol. 1997;31(7):655-661.

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Abstract PDF: Proliferations of the endometrial glands form a continuum from focal glandular crowding through simple hyperplasia, complex hyperplasia and atypical hyperplasia to frank adenocarcinoma. But objective criteria to distinguish these proliferative endometrial lesions are not clear-cut and terminology is confusing. The p53 protein is a nuclear phosphoprotein that can regulate cell proliferation and suppress tumor growth. Mutation in the p53 gene have been reported in a variety of human tumors, and in selected malignancies overexpression of p53 has been associated with poor prognosis. In this study we examined a series of endometrial proliferative lesion, including hyperplasia, adenocarcinoma, and adenomyosis to determine whether or not p53 is overexpressed in these lesions. In the result, p53 immunoreactivity was observed in 3 of 17 (17.6%) simple hyperplasia, one of 6 (16.6%) complex hyperplasia, none of 3 (O%) atypical hyperplasia, 6 of 13 (46.1%) adenocarcinoma and none of 10 (O%) adenomyosis. In conclusion, p53 mutation seems to play a role in oncogenesis of endometrial adenocarcinoma in early phase but there was no significant relationship between p53 overexpression and histologic grade of adenocarcinoma.

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.

Expression of p53 Protein in Endometrial Carcinoma.: Mi Jin Kim, Dong Suk Kim; Korean J Pathol. 1999;33(5):347-352.

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Abstract PDF: The mutation of p53, a tumor suppressor gene, has been considered to play an important role in tumorigenesis in a variety of human cancers and the abnormal expression of p53 are frequently associated with poor prognosis. In order to examine the association of p53 overexpression with known prognostic factors including estrogen receptors (ER) and progesterone receptors (PR), we studied the status of p53 protein expression by immunohistochemical staining of paraffin sections of 29 endometrial carcinoma (25 endometrioid carcinoma, 2 clear cell carcinoma, and 2 serous carcinoma), obtained from hysterectomy. The results were as follows: The expression of p53, ER, and PR was present in 9/29 (31%), 3/29 (16%), and 12/29 (48%), respectively. The expression of p53 in endometrioid adenocarcinoma was present in 6/25 (24%) and showed significant correlation with histologic grade, nuclear grade, and myometrial invasion. The status of PR showed significant inverse correlation with histologic grade, nuclear grade and myometrial invasion. There was no significant correlation between ER status and these histologic factors. The expression of p53 was inversely associated with the status of PR, but statistically not significant. Our results indicate that p53 may be useful in predicting prognosis in endometrial carcinoma and will be able to provide helpful information in predetermination of aggressive behavior of the tumor in evaluation of curettage specimen.

Expression of MIB-1 in Endometrial Adenocarcinoma: Correlation with p53 Protein Expression and Histologic Prognostic Factors.: Mi Jin Kim, Young Ran Shim, Dong Sug Kim; Korean J Pathol. 1999;33(12):1146-1151.

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Abstract PDF: The evaluation of the proliferative potential of malignant neoplasm is of major interest for predicting their biological behavior. MIB-1, a monoclonal antibody against the Ki-67 antigen, is a marker of cell proliferation, which is widely applied to human cancers recently. To assess the growth potential of uterine endometrial carcinoma, we performed immunohistochemical staining of MIB-1 in 34 cases of endometrial adenocarcinoma (endometroid type) from the paraffin sections. We evaluated its correlation with p53 overexpression and known prognostic factors including FIGO grade, nuclear grade, myometrial invasion, and estrogen and progesterone receptors. As a result, the MIB-1 labelling index was significantly correlated with FIGO grade, nuclear grade and myometrial invasion (p<0.05) and there was no significant correlation between MIB-1, ER or PR status. The expression of p53 protein showed significant correlation with FIGO grade and nuclear grade (p<0.05) and there was no significant correlation among p53 protein, myometrial invasion, ER and PR status. The MIB-1 labelling index revealed striking difference between p53 positive and p53 negative group (p<0.05). We concluded that MIB-1 labelling index is associated with poor prognostic parameter in endometrial adenocarcinoma, and may be a useful marker for predicting tumor of high grade and deep myometrial invasion, if MIB-1 labelling index is more than 50% and is accompanied by p53 overexpression.

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