Neoplastic Endometrium Research Articles

Comparative Study of Immunohistochemical Expression of ER and PR as Prognostic Markers and Correlation with Clinicopathological Parameters in Human Endometrial Adenocarcinoma

In human steroid sensitive tissue, progesterone receptors (PRs) and estrogen receptors (ERs) have been demonstrated at the mRNA and/or protein levels by using molecular biology and immunohistochemistry techniques. Estrogen and progesterone receptors are present both in endometrial hyperplasia and in neoplastic endometrium. The aim of the present work was to compare the expression of ER and PR as prognostic biomarkers in human endometrial adenocarcinoma versus benign tumors and normal endometrial tissues as well as their correlation with different pathological and histological parameters. Immunohistochemical technique was used to examine the expression of ER and PR in normal, benign as well as in endometrial adenocarcinoma. Present results showed higher expression of ER and PR in endometrial adenocarcinoma comparing to normal and benign endometrial tissues.

Vitamin D receptor and cellular retinol-binding protein-1 immunohistochemical expression in normal, hyperplastic and neoplastic endometrium: Possible diagnostic and therapeutic implications

BackgroundWe conducted this study to assess the effect of VDR and CRBP-1 immunohistochemical expression on the endometrium and to explore their role in endometrial cancer carcinogenesis. MethodsThis study comprised two hundred paraffin-embedded endometrial tissue samples diagnosed as 42 and 63 proliferative and secretory endometrium respectively, 45 endometrial hyperplasias with atypia and 50 endometrial carcinomas (25 low-grade and 25 high-grade endometrial carcinomas). The immunohistochemical method was done to determine the expression of VDR and CRBP-1. ResultsVDR was strongly expressed in 8 (17.8%) cases with endometrial hyperplasia, 15 (60%) cases with low-grade endometrial carcinoma, and 22 (88%) cases with high-grade endometrial carcinoma. While CRPB1 overexpression was noted in cases with proliferative endometrium, secretory endometrium and endometrial hyperplasia with atypia, 37 (88.1%), 56 (88.9%) and 3 (6.7%) cases respectively and all malignant cases showed negative expression. ConclusionsIncreased VDR expression and reduced CRBP-1 expression are associated with malignant features of the endometrium with a significant statistical difference of immunoreactivity between groups of normal endometrium, hyperplastic changes & carcinoma. Our data suggested that increased VDR expression is partly associated with endometrial cancers through a premalignant phase. Also, increased VDR and reduced CRBP-1 expression are associated with the progression of endometrial carcinoma with higher grades.

Expression of Laminin Receptor 1 in Normal, Hyperplastic, and Malignant Endometrium.

Laminin receptor 1 may have a role in the progression from endometrial hyperplasia with or without atypia to endometrial cancer. Therefore, we aimed to investigate the pattern, percentage, and intensity of laminin receptor 1 expression in normal, hyperplastic, and neoplastic endometrium. Paraffin blocks of 131 specimens with the diagnoses of normal endometrium (n=25), endometrial hyperplasia with atypia (n=21) or without atypia (n=55), and endometrial cancer (n=30) were immunostained with laminin receptor 1 antibody, and its expression percentage, pattern, and intensity in the epithelial cytoplasm, basement membrane, and endometrial stroma of these tissues were assessed. When compared with hyperplasia with or without atypia and endometrial cancer, the percentage of nonstaining with laminin receptor 1 in the epithelial basement membrane was higher (96%), and the percentage of <50% staining with laminin receptor 1 was lower (4%) in the normal endometrium (P=0.001). While a progressive increment in staining percentage and density of epithelial cytoplasm and basement membrane was noted through an orderly progression from normal endometrium to endometrial hyperplasia without atypia, endometrial hyperplasia with atypia, and cancer of endometrium (P<0.001), such a relationship was not found for the staining percentage and density of endometrial stroma (P>0.05). Disease progression-related gradual increment in laminin receptor 1 expression in the epithelial basement membranes of hyperplastic endometrium with or without atypia and cancer of endometrium reveals that it may play a substantial role in the transition from premalignant to the malignant state of endometrial lesions.

Study of expression of PTEN and Cyclin D1 in endometrium at a tertiary care centre

Background: To study the expression of PTEN (Phosphatase and Tensin homologue) and Cyclin D1 in normal, hyperplastic and neoplastic endometrium by immunohistochemistry and to corroborate the interrelationship between PTEN and Cyclin D1 in normal to neoplastic endometrial disorders including endometrial carcinoma.Methods: Formalin fixed paraffin embedded (FFPE) sections of spectrum of endometrium in fifty different cases were taken from secretory phase to endometrial carcinoma and subjected to Immunohistochemistry using PTEN and Cyclin D1 .Results: Immunoreactivity was regarded as positive when brown staining was localized in the nuclei or cytoplasm. The intensity of nuclear staining was graded from 0 to 3+ and the extent was semi quantitatively estimated. If less than 10% of cells were positive a score of 0 was given, 11 % to 30% cell positivity was scored as 1+, 31% to 60 % positivity was scored as 2+ and more than 60% positive cells was labelled as 3+. Statistical analysis was performed with Chi-Square test and significant differences were noted between these 3 groups (p value &lt; 0.05).Conclusions: The present study supports that an inverse correlation exists in the expression of PTEN and Cyclin D1 in normal, hyperplastic and neoplastic endometrium. The decreased PTEN expression is a marker of the earliest endometrial premalignant lesions, and we propose that use of PTEN immunostaining may be informative in identifying premalignant lesions that are likely to progress to carcinoma. Cyclin D1 expression in endometrial glands increases progressively in intensity and extent from normal endometrium to hyperplasia to carcinoma.

Autotaxin is a novel molecular identifier of type I endometrial cancer

Endometrial cancer is the most common cancer of the female genital tract in Western Countries, with an incidence of 150.000 new cases/year. Despite high incidence, little is known about the molecular pathogenesis of this tumor. Phospholipids including lysophosphatidic acid (LPA) are involved in proliferation and dissemination of cancer. LPA is a potent bioactive phospholipid synthesized by autotaxin (ATX) through its lysophospholipase D activity. Recent evidence suggests that the ATX/LPA signaling axis plays a role in endometrial cancer. We carried out a prospective study involving two groups of patients classified in accordance to hysteroscopic-guided biopsy. Patients with histological diagnosis of endometrial cancer were enrolled into group one, whereas control patients with pelvic organ prolapse were assigned group two. Both groups underwent hysterectomy, with either open or laparoscopic surgery. After uterine extraction, a second endometrial biopsy was performed to collect tissues. Real-Time PCR was performed to evaluate ATX gene expression in collected tissues. Statistical analysis including unpaired two-way or one-way Student's t test and ANOVA was performed. We found ATX gene expression significantly higher in neoplastic endometrium compared with normal tissue (P value = 0.0002). In particular, the expression of ATX was significantly elevated in type I endometrial cancer (i.e., endometrioid histotype) compared to type II, in premenopausal women and in patients affected either by obesity (BMI > 30) or diabetes. We propose ATX as a novel potential biomarker particularly implicated in the pathobiology of type I endometrial cancer. Also, we propose ATX as a useful theranostic target in endometrial cancer.

Steroid Receptor Coactivator-2 Controls the Pentose Phosphate Pathway through RPIA in Human Endometrial Cancer Cells

Steroid receptor coactivator-2 (SRC-2) is a transcriptional coregulator that modulates the activity of many transcription factors. Levels of SRC-2 are elevated in endometrial biopsies from polycystic ovary syndrome patients, a population predisposed to endometrial cancer (EC). Increased expression of SRC-2 is also detected in neoplastic endometrium suggesting a causal link between elevated SRC-2 expression and the emergence of endometrial disorders that can lead to cancer. Here, we reveal that SRC-2 knockdown reduces EC cell proliferation and anchorage-independence. Additionally, SRC-2 is required to maintain cellular glycolytic capacity and oxidative phosphorylation, processes essential for EC cell proliferation. Importantly, SRC-2 is critical for the normal performance of the pentose phosphate pathway (PPP). Perturbation of the PPP due to loss of SRC-2 expression may result from the depletion of ribose-5-P isomerase (RPIA), a key enzyme of the PPP. As with SRC-2, RPIA knockdown reduces EC cell proliferation, which is accompanied by a decrease in glycolytic capacity and oxidative phosphorylation. Glucose metabolite tracking experiments confirmed that knockdown of SRC-2 and RPIA downregulates the metabolic rate of both glycolysis and the PPP, highlighting a novel regulatory cross-talk between glycolysis and the PPP modulated by SRC-2.

Significance of matrix metalloproteinase-1 and -3 gene polymorphisms and their expression in normal and neoplastic endometrium

BackgroundMatrix metalloproteinases (MMPs) play a fundamental role in tissue degradation or remodeling and involved in all stages of tumor progression. However, the role of the MMPs polymorphisms with endometrial carcinoma has not been fully examined in Egyptian patients. Therefore, we planned this study to evaluate associations of the MMP-1 (−1607 1G/2G) and MMP-3 (−1171 5A/6A) polymorphisms and their immune reactive protein combinations with endometrial carcinoma susceptibility and prognosis in Egyptian patients. MethodsParaffin-embedded tissue samples from 40 women with endometrial carcinoma and 30 controls were immunohistochemically stained for MMP-1and MMP-3 expression. Tissue MMPs levels were analyzed by ELISA technique, and tissue samples were genotyped for MMP-1 and MMp-3 gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Resultswe recorded a significant increase of MMP-1 levels in endometrial carcinoma patients more than controls, to be more increased with advanced stages and grades of the carcinoma. Whereas, the MMP-3 tissue levels showed non-significant changes among patients and controls and even among different stages and grades of cancer.Patients with endometrial carcinoma exhibited a higher distribution of MMP-11G/2G or 2G/2G genotypes compared with controls. Tumors containing the 2G allele expressed MMP-1 protein more frequently than those of 1G/1G genotype. The overall genotype and alleles distribution of the MMP-3 polymorphism in patients was not different from that of controls. The haplotype 2G-6A was associated with a significantly increased risk of endometrial carcinoma as compared with the 1G-5A haplotype. ConclusionThe MMP-1 (−1G/2G) SNP and MMP 2G/6A haplotype may modify susceptibility and are associated with a higher risk of endometrial carcinoma. Otherwise, the MMP-3 (5A/6A) promoter SNP is unlikely to be associated with endometrial carcinoma in the Egyptian population.

Expression of cyclin d1 in normal, hyperplastic and neoplastic endometrium

Expression of cyclin d1 in normal, hyperplastic and neoplastic endometrium

The SGK1 inhibitor SI113 induces autophagy, apoptosis, and endoplasmic reticulum stress in endometrial cancer cells.

Endometrial cancer is often characterized by PI3K/AKT pathway deregulation. Recently it has been suggested that SGK1, a serine/threonine protein kinase that shares structural and functional similarities with the AKT family, might play a role in cancer, since its expression and/or activity has been found to be deregulated in different human tumors. However, the role of SGK1 in endometrial cancer has been poorly investigated. Here, we show that SGK1 expression is increased in tissue specimens from neoplastic endometrium. The SGK1 inhibitor SI113 induced a significant reduction of endometrial cancer cells viability, measured by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. This effect was associated to the increase of autophagy, as revealed by the increase of the markers LC3B-II and beclin I, detected by both immunofluorescence and western blot analysis. SI113 treatment caused also apoptosis of endometrial cancer cells, evidenced by the cleavage of the apoptotic markers PARP and Caspase-9. Intriguingly, these effects were associated to the induction of endoplasmic reticulum stress markers GRP78 and CHOP evaluated by both Real-Time RT-PCR and Western Blot analysis. Increased expression of SGK1 in endometrial cancer tissues suggest a role for SGK1 in this type of cancer, as reported for other malignancies. Moreover, the efficacy of SI113 in affecting endometrial cancer cells viability, possibly via endoplasmic reticulum stress activation, identifies SGK1 as an attractive molecular target for new tailored therapeutic intervention for the treatment of endometrial cancer.

A study of PTEN expression in endometrial hyperplasia and endometrioid type of endometrial carcinoma

Background: To analyze the role of PTEN expression in hyperplastic and neoplastic endometrium by immunohistochemistry and to find the grades of PTEN expression in neoplastic, hyperplasic and normal endometrium. Methods: 100 numbers of endometrial samples were studied retrospectively. The tissue were fixed in formalin and taken up for routine histopathological and immunohistochemistry studies. Results: In our study PTEN is well expressed in a score of 2+ and 1+ in cyclical endometrium and hyperplasia without atypia whereas altered PTEN expression was noted in atypical hyperplasias and endometroid type of endometrial carcinoma in a score of 0and 1+. Conclusion: The current study proved that PTEN expression is down regulated in endometrial pathological condition. Immunohistochemical evaluation of PTEN expression was useful in screening precancerous hyperplasia lesions and detecting earliest stage of endometrial carcinogenesis.

Immunohistochemical expression of cyclooxygenase-2 (COX-2) in feline endometrial adenocarcinoma and in normal and hyperplastic endometria.

Cyclooxygenase-2 (COX-2) is overexpressed in several human and animal neoplasms, including the human endometrial carcinoma. It has been suggested as a prognostic marker and a potential therapeutic target. This study aimed to (i) clarify histological aspects of feline endometrial adenocarcinomas (FEA) of the papillary serous type and (ii) characterize COX-2 immunohistochemical expression in normal, hyperplastic and neoplastic endometrium in this species. Archived paraffin-embedded tissue samples of 33 FEA, eight cystic endometrial hyperplasias (CEHs) and 21 samples of normal, healthy endometrium in the follicular (FS; n = 10) and luteal (LS; n = 11) stages were evaluated. Histological evaluation of haematoxylin and eosin-stained sections of the FEA revealed a papillary proliferation of neoplastic cells of serous type, accompanied by clear and multinucleated cells. Other architectural arrangements mainly included solid and tubular growth. Randomly distributed areas of necrosis within the tumours were commonly observed. Invasion of the myometrium, of the serosa and of the vascular and/or lymphatic vessels was not constant features. The mean number of mitoses was higher in FEA compared to non-neoplastic endometrium. COX-2 scores were lower in FEA (p = 0.003) and CEH (p = 0.05) when compared to normal epithelium (NE). The loss of the membrane apical reinforcement in epithelial cells was observed in FEA samples, which was accompanied by the dislocation of COX-2 labelling into the cytoplasm and the perinuclear area; in contrast, in epithelial cells in the healthy and hyperplastic endometria, the immunoreaction showed the characteristic pattern of apical membrane reinforcement, suggestive of the membrane polarization. COX-2 epithelial scores were higher in the FS than in the LS. No differences were found in stromal COX-2 expression between normal, CEH and FEA groups, but it was higher in the LS than in the FS. In summary, loss of COX-2 compartmentalization in neoplastic epithelial cells might be one of the molecular events underlying endometrial carcinogenesis.

Immunohistochemical Expression of Heparanases 1 and 2 in Benign Tissue and in Invasive Neoplasia of the Endometrium: A Case-Control Study

Our purpose was to compare the expression of heparanase isoforms, in normal and in neoplastic endometrium. In a pioneering way, we sought to evaluate the expression of heparanase 1 (HPSE1) and heparanase 2 (HPSE2) in glandular and in stromal tissues. This is a case-control study, conducted retrospectively in a public hospital, using paraffin blocks of endometrial tissue from patients admitted from 2002 to 2011 with and without endometrial cancer, with regard to the immunohistochemical expression of HPSE1 and HPSE2. The paraffin blocks were used for tissue microarray analysis and immunohistochemistry study in glandular and stromal tissues. In the study period, 195 participants were enrolled, 75 with and 120 without cancer. There was no significant difference between them regarding HPSE1 expression, both in gland and in stromal tissues. Heparanase 1 expression in the glandular tissue was more frequent among those with high-grade carcinoma, compared with patients with carcinoma type I. The difference in the expression of HPSE2 was significant between groups: it was less frequent in the controls than in the patients with cancer in the glandular tissue. In the stromal tissue, HPSE2 expression was significantly higher in the controls than in the patients with cancer and different when patients of the secretory endometrium subgroup were compared with those with hypotrophic, proliferative endometriums or with architectural disorders. No significant difference was found in the heparanase expressions in patients with cancer according to prognosis factors. Heparanase 1 is more intensely expressed in the glandular tissue of high-grade compared with type I carcinomas. Heparanase 2 is more intensely expressed in the glandular tissue of cancer than in nonneoplastic endometrium, whereas the HPSE2 expression in the stromal tissue is higher in the nonneoplastic controls compared with the group of patients with cancer mainly in the secretory endometrium. This suggests that HPSE2 might be stimulated by progesterone, with a possible antineoplastic role, antagonist to HPSE1, to be further investigated.

Decreased hyaluronidase 1 expression is associated with early disease recurrence in human endometrial cancer

ObjectiveHyaluronidases (HYAL1 and HYAL2) are key enzymes in the degradation of hyaluronan, and their expression has been altered in various cancer types. We previously showed that hyaluronan accumulation in endometrial carcinomas was correlated with decreased mRNA expression of the HYAL genes. In this study, we analyzed HYAL1 and HYAL2 protein expressions in normal and precancerous endometrial tissues and in endometrial carcinomas. We also investigated whether the protein levels were associated with clinicopathological factors, invasion, and disease recurrence. MethodsA total of 343 tissue specimens from normal, atrophic, hypertrophic, and neoplastic endometria were analyzed immunohistochemically for HYAL1 and HYAL2 expressions. The results were correlated with clinicopathological factors, the expression of the epithelial–mesenchymal transition marker, E-cadherin, and disease recurrence. ResultsReduced HYAL1 expression was associated with the progression of endometrial carcinomas towards higher grades and also with large tumor sizes, lymph node metastasis, and lymphovascular invasion. Reduced expression of both HYAL1 and HYAL2 was associated with deep myometrial invasion. HYAL2 expression was primarily constant in neoplastic tissues, but its expression was altered in different phases of the endometrial cycle. In addition, a reduction in HYAL1 expression was associated with the depletion of E-cadherin. In a multivariate analysis, reduced HYAL1 expression was an independent prognostic factor for early disease recurrence (HR 5.13, 95% CI: 1.131–23.270, p=0.034). ConclusionsThis study showed that reduced HYAL1 expression was associated with endometrial carcinoma aggressiveness, which further supported the role of hyaluronan degradation in cancer progression.

Cyclin D1 and Ki-67 expression in normal, hyperplastic and neoplastic endometrium.

Background:Proliferation and differentiation of cancer cells are regulated by various cell cycle promoting and inhibiting factors. Our knowledge about these proteins and mechanisms regulating cell cycle progression has increased dramatically in recent years.Aim:The present study was undertaken to examine the expression profile of cell cycle regulatory proteins in normal proliferative endometrium, hyperplasias (simple, complex and atypical) and endometrial carcinoma in a quantitative approach as also to assess correlations of Cyclin D1 expression with Ki-67 a proliferation marker.Settings and Design:A retrospective case control study in a tertiary referral centre.Materials and Methods:We evaluated and compared the expression profile of Cyclin D1 and Ki-67 expressions in 61 endometrial samples submitted as either endometrial curetting or hysterectomy specimens, which were diagnosed as simple hyperplasia (n =11), complex hyperplasia (n = 13), atypical hyperplasia (n = 7), and endometrial carcinoma (n = 20).Results:There was increased expression of Cyclin D1 and Ki-67 in patients with endometrial carcinoma relative to proliferative endometrium and simple hyperplasia, but there was no such difference between cases of atypical hyperplasia and endometrial carcinoma. Cyclin D1 expression had a positive correlation with Ki-67 expression. Cyclin D1 together with Ki-67 may be a marker for endometrial carcinogenesis and tumor cell proliferation.

استظهار المعلمات النسيجية المناعية(TTF-1, CK-7 and CK-20) في نسيج بطانة الرحم لورمي وغير الورمي

ان بطانة الرحم تتكون من نسيج مخاطي غدي يقع فوق طبقة من النسيج البيني المتخصص وكلاهما يتغير بالهيئة والوظيفة استجابة" للتغيرات الهرمونية الفسلجية والمرضية مؤدية الى حالات ورمية وغير ورمية. ان سرطان بطانة الرحم يعتبر من اورام الجهاز التناسلي الانثوي الشائعة وله معلمات نسيجية مناعية معروفة يعد بروتين عامل النسخ الدرقيTTF-1 من البروتينات المعروفة باستظهارها نسيجيا في نسيج الغدة الدرقية&nbsp; نسيج الرئة الطبيعي والورمي. مع ذلك تظهر دراسات حديثة استظهار هذه الدالة المناعية النسيجية في انسجة الجسم الأخرى الطبيعية والورمية محاولة توضيح دوره في تلك الانسجة. هذه الحقيقة يجب الاخذ بها بنظر الاعتبار عند تشخيص الاورام السرطانية الغديه اخرى اهمها الكيراتين الخلوي رقم 7 ورقم&nbsp; 20 CK 7 و&nbsp; CK 20حيث ان لهما استظهارا متناسقا في مختلف الأورام السرطانية الغدية. هدف الدراسة: هو معرفة مقدار استظهار الدالة المناعية TTF-1 &nbsp;في بطانة الرحم الورمية وغير الورمية. هذا بالاضافة الى الاستظهار المتناسق للكيراتين الخلوي رقم 7 ورقم 20. الطرق البحثية والمواد: تم دراسة استظهار الدالة المناعية TTF-1 في ست وثلاثون حالة منها اثنتان وعشرون حالة سرطانية وثلاث عشرة حالة غير ورمية لبطانة الرحم. هذا بالاضافة الى دراسة الاستظهار المتناسق للدالتين CK7 و CK20 . النتائج: اظهرت الدراسة استظهار الدالة TTF-1 &nbsp;في حالتين من حالات سرطان بطانة الرحم وعدم استظهارها في أي من الحالات الغير ورمية. كما واستظهرت الدالة المناعية CK7 &nbsp;&nbsp;في احدى وعشرين من ثلاث وعشرين حالة من حالات سرطان بطانة الرحم (بمستوى استظهار مختلف) وفي جميع عينات بطانة الرحم اللاورمية فيما لم تستظهر الدالة المناعية CK20 في أي من الحالات الورمية وغير الورمية . المناقشة: على الرغم من ان الدالة المناعية النسيجيةTTF-1 تعتبر دالة مميزة لنسيج الغدة الدرقية ونسيج الرئة فان استظهارها في انسجة اخرى ورمية وغير ورمية (بضمنها نسيج بطانة الرحم) يجب الاخذ به بنظر الاعتبار خاصة عند تشخيص حالات السرطان الغدي المنتشر. ان دور الدالةTTF-1 في تطور ونمو بطانة الرحم وعلاقته بمخاطر زيادة نسبة الاصابة بسرطان بطانة الرحم لم يمكن التوصل اليه في هذه الدراسة لعدم استظهاره في اي من الحالات الغير ورمية.ان طريقة استظهار الدالة CK 7 &nbsp;في الانسجة الورمية وغير الورمية في بطانة الرحم قد يلقي الضوء على الدور الممكن لها في دراسة وظيفة بطانة الرحم.

Ekspresja i znaczenie prognostyczne glikoproteiny 72 towarzyszącej nowotworom ocenianej metodami immunohistochemicznymi w normalnym, rozrostowym i nowotworowym endometrium

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Mızrak T, Uysal A, Taner C, Bayol Ü. The expression and prognostic significance of the tumour-associated glycoprotein 72 in the normal, hyperplastic and neoplastic endometrium using immunohistochemical methods. Menopause Review/Przegląd Menopauzalny. 2013;12(3):202-206. doi:10.5114/pm.2013.36583. APA Mızrak, T., Uysal, A., Taner, C., & Bayol, Ü. (2013). The expression and prognostic significance of the tumour-associated glycoprotein 72 in the normal, hyperplastic and neoplastic endometrium using immunohistochemical methods. Menopause Review/Przegląd Menopauzalny, 12(3), 202-206. https://doi.org/10.5114/pm.2013.36583 Chicago Mızrak, Tolga, Ahmet Uysal, Cüneyt Eftal Taner, and Ümit Bayol. 2013. "The expression and prognostic significance of the tumour-associated glycoprotein 72 in the normal, hyperplastic and neoplastic endometrium using immunohistochemical methods". Menopause Review/Przegląd Menopauzalny 12 (3): 202-206. doi:10.5114/pm.2013.36583. Harvard Mızrak, T., Uysal, A., Taner, C., and Bayol, Ü. (2013). The expression and prognostic significance of the tumour-associated glycoprotein 72 in the normal, hyperplastic and neoplastic endometrium using immunohistochemical methods. Menopause Review/Przegląd Menopauzalny, 12(3), pp.202-206. https://doi.org/10.5114/pm.2013.36583 MLA Mızrak, Tolga et al. "The expression and prognostic significance of the tumour-associated glycoprotein 72 in the normal, hyperplastic and neoplastic endometrium using immunohistochemical methods." Menopause Review/Przegląd Menopauzalny, vol. 12, no. 3, 2013, pp. 202-206. doi:10.5114/pm.2013.36583. Vancouver Mızrak T, Uysal A, Taner C, Bayol Ü. The expression and prognostic significance of the tumour-associated glycoprotein 72 in the normal, hyperplastic and neoplastic endometrium using immunohistochemical methods. Menopause Review/Przegląd Menopauzalny. 2013;12(3):202-206. doi:10.5114/pm.2013.36583.

STn is a Novel Biomarker for Type�? Endometrial Carcinoma*

Sialyl-Tn(sTn) is a tumor-associated carbohydrate antigen overexpressed in many carcinomas.But whether it is expressed in neoplastic human endometrium is controversial.Here we screened 111 clinical samples including 82 endometrial cancers,16 atypical hyperplastic and 13 normal endometria,by immunohistochemistry using a novel anti-sTn antibody,namely 3P9.Our results showed that the expression of sTn in the endometrial carcinoma was significantly higher(76%) than that in normal tissues(31%)(P 0.01) and in atypical hyperplasia(44%)(P 0.05).Importantly,we found that sTn expression in typeⅠ carcinoma(80%) was obviously higher than that in typeⅡ(45%)(P 0.05).These results suggested that sTn may be a biomarker for endometrial carcinoma,especially for typeⅠcarcinoma.Moreover,we observed that sTn expression was increased with the decline of tumor histological grade(P 0.05),indicating that sTn was associated with a favorable prognosis in endometrial carcinoma.

Endoplasmic reticulum stress is activated in endometrial adenocarcinoma

ObjectivesEndometrial cancer is the most common malignancy of the female genital tract. However, in spite of a huge advance in our understanding of endometrial cancer biology, therapeutic modalities haven't significantly changed over the past 40years. The activation of the Unfolded Protein Response (UPR) and GRP78 increase following Endoplasmic Reticulum (ER) stress have been recently identified as mechanisms favoring growth, invasion and resistance to therapy of different types of cancer. However, a possible role of ER stress and GRP78 in endometrial cancer has never been investigated. MethodsTissue specimens from normal and neoplastic endometrium were analyzed for the expression of the ER stress markers GRP78, ATF6 and CHOP by Real-Time RT-PCR. In addition, GRP78 protein expression and localization were evaluated by Western blot and immunohistochemistry, respectively. The effect of GRP78 knock down on cell growth of Ishikawa cells was analyzed by proliferation curve analysis. ResultsIn this analysis, the expression levels of GRP78, ATF6 and CHOP mRNAs were significantly increased in specimens of endometrioid endometrial carcinomas. GRP78 and ATF6 protein expression levels were also increased in specimens of endometrial adenocarcinomas. GRP78 knock down caused a decrease of Ishikawa cells' growth. ConclusionsThe increased expression of ER stress markers in endometrioid endometrial carcinomas suggests a role for ER stress, the UPR and, possibly, GRP78 in endometrial cancer. Whether these mechanisms have a substantial function in the pathogenesis of malignant transformation of human endometrium is still under investigation in our laboratory.

Crosstalk Between Estrogen Receptor and Mitogen-Activated Protein Kinase Signaling in the Development and Progression of Endometrial Cancer

The objectives of the study were to evaluate the role of mitogen-activated protein kinase (MAPK) signaling in normal, hyperplastic, and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether 17β-estradiol (E2) and tamoxifen (TAM) mediate the proliferation and apoptosis of endometrial cancer cells through the MAPK pathway. The expressions of phosphorylated and total extracellular signal-regulated kinases 1/2 (phosphorylated extracellular signal-regulated kinase 1/2 [p-ERK1/2] and total ERK1/2 [t-ERK1/2]) were analyzed with immunohistochemistry in normal, hyperplastic, and neoplastic endometrium. The expression levels of p-ERK1/2 and t-ERK1/2 in RL95-2 and KLE after stimulation by E2, progesterone (P), and TAM were detected by Western blotting. The effects of E2 and TAM in combination with MAPK pathway inhibitors on the growth and apoptosis of endometrial cancer cells were examined by the MTS assay and flow cytometry analysis. The expression level of p-ERK1/2 was significantly associated with the International Federation of Gynecology and Obstetrics stage (P = 0.0072). The ratio of phosphorylated/total ERK1/2 was higher in ER-positive endometrial cancer tissues and cells (P < 0.05). 17β-Estradiol increased ERK1/2 phosphorylation, and TAM decreased ERK1/2 phosphorylation in endometrial cancer cell lines within 30 minutes (P < 0.05). The MEK1/2 inhibitor, U0126, and the stress-activated protein kinase/c-Jun NH2-terminal kinase inhibitor, SP600125, significantly suppressed the proliferation of human endometrial cancer cell lines RL95-2 and KLE induced by E2 (P < 0.05). The level of TAM-induced apoptosis was greater in KLE than in RL95-2 cells, and the p38 cascade was involved in the TAM-induced apoptosis of both cell lines (P < 0.05). The cross-talk between MAPK signaling and ER status might exert a key role in progression of endometrial cancer. Furthermore, the effects of E2 or TAM on the proliferation or apoptosis of ER-positive and ER-negative endometrial cancer cells were mediated through distinct MAPK pathways. These mechanisms might contribute to ER-specific differences in MAPK activation for molecular-target therapies in endometrial carcinoma.

Immunohistochemical expression of keratan sulfate: a possible diagnostic marker for carcinomas of the female genital tract

AimsThe authors previously reported the expression of keratan sulfate (KS), a glycosaminoglycan, in the epithelium of normal and neoplastic endometria. The aim of this study was to evaluate its potential...