cyclin-d1 and Carcinoma--Endometrioid

Poorly differentiated malignant neoplasms involving the gynecologic tract routinely include a poorly differentiated endometrial carcinoma (EC) in the differential diagnosis. Some nuclear lineage/site-specific immunohistochemical markers are utilized in this diagnostic setting including SATB2, cyclin D1, SALL4, and BCOR, but their specificity and use in small samples are not clear across the spectrum of ECs. Cases of undifferentiated/dedifferentiated endometrial carcinomas (UEC/DDEC), clear cell carcinoma (CCC), uterine serous carcinoma (USC), FIGO grade 3 endometrial endometrioid carcinoma (EEC), and uterine carcinosarcoma (UCS) were identified and diagnoses confirmed. Whole-section immunohistochemical stains for SATB2, cyclin D1, SALL4, BCOR, and PAX8 were performed. A total of 113 cases were utilized: 15 CCC, 26 EEC, 19 UCS, 22 USC, and 31 UEC/DDEC. Cases were distributed across both low (49%) and high (51%) FIGO clinical stages. SATB2 was expressed by UCS (8/19, 42%), EEC (10/26, 38%), UEC/DDEC (11/30, 37%), and USC (6/22, 27%). Cyclin D1 was expressed by EEC (24/26, 92%), USC (17/22, 77%), UEC/DDEC (15/20 EEC component, 75%; 22/30 UEC, 73%), UCS (10/16 carcinoma, 63%; 11/19 sarcoma, 58%), and CCC (8/15, 53%). SALL4 was expressed most frequently by UEC/DDEC (12/30, 40%), but also USC (7/22, 32%), EEC (5/26, 19%), and UCS (4/16 carcinoma, 25%; 3/19 sarcoma, 16%). BCOR was expressed at low levels in 2 USC, 2 UEC/DDEC, and 2 UCS. PAX8 was generally positive but showed lower expression in UEC/DDEC (17/30, 57%) and in the sarcomatous portions of UCS (6/19, 32%). SATB2, cyclin D1, SALL4, and BCOR stain variable numbers of poorly-differentiated EC and must be carefully interpreted within morphologic and clinical context.

Topics: Carcinoma, Endometrioid; Cyclin D1; Endometrial Neoplasms; Female; Humans; Matrix Attachment Region Binding Proteins; Proto-Oncogene Proteins; Repressor Proteins; Sarcoma; Transcription Factors; Uterine Neoplasms

The present study discusses the expression and effect of the SOX17 gene in endometrioid adenocarcinoma. MTT assay is performed to determine the growth inhibition ratio of the DNA methyltransferase inhibitor 5-AZA for endometrial carcinoma cells, and the real-time fluorescence quantification PCR (qRT-PCR) was used to detect the mRNA expression of SOX17, β-catenin, and CyclinD1 in endometrial carcinoma tissues before and after using 5-AZA to treat the endometrial carcinoma cell line. There were 30 cases on endometrioid adenocarcinoma tissues and 10 cases on normal endometrial tissues. The results revealed that the expression of SOX17 in endometrioid adenocarcinoma tissues was downregulated (P < 0.05), the expression of β-catenin and CyclinD1 was upregulated (P < 0.05), and the expression of SOX17, CyclinD1, and β-catenin was negatively correlated (r = -0.353, P > 0.05; R = -0.463, P < 0.05). The higher the histological grade and FIGO staging were, the lower the expression level of SOX17 was (P < 0.05). After HEC1A cells were treated by 5-AZA, the cell growth inhibition was most obvious (IC

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Azacitidine; beta Catenin; Carcinoma, Endometrioid; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Down-Regulation; Endometrial Neoplasms; Endometrium; Female; Gene Expression Regulation, Neoplastic; Humans; Hysterectomy; Immunohistochemistry; Middle Aged; Neoplasm Grading; SOXF Transcription Factors; Up-Regulation; Wnt Signaling Pathway

Endometrial endometrioid carcinomas (EECs) account for >80% of endometrial carcinomas (ECs). Continuous stimulation of the endometrium by estrogen is a risk factor for the tumorigenesis of estrogen receptor (ER) α-positive EEC. MicroRNA-22 (miR-22) has been reported to be implicated in the regulation of various types of cancer and directly targets ERα. However, an exact regulatory mechanism between miR-22 and ERα in EEC has yet to be investigated. To the best of our knowledge, the present study demonstrated for the first time that the expression of miR-22 was significantly downregulated in ERα-positive EEC tissues and cell lines, RL95-2 and Ishikawa, when compared with that in normal endometrium and ERα-negative EEC samples. This indicated that miR-22 may be important in ERα-positive EEC, possibly through an estrogen-dependent mechanism. miR-22 mimics were then transfected into RL95-2 and Ishikawa cells, respectively, and revealed that the introduction of miR-22 markedly downregulated the mRNA and protein levels of ERα. Further investigation demonstrated that miR-22 was able to effectively reverse 17β-estradiol (E2)‑induced cell proliferation, cell cycle progression and invasion of ERα-positive RL95-2 and Ishikawa cells, at least partially through inhibiting the expression of Cyclin D1 as well as the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. In conclusion, the present study, to the best of our knowledge, was the first to reveal an inhibitory role of miR-22 in ERα-positive EEC tissues and cells, indicating that miR-22 may be a novel candidate for the endocrine therapy of ERα-positive EEC.

Topics: Carcinoma, Endometrioid; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Estradiol; Estrogen Receptor alpha; Female; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasm Invasiveness; Ovarian Neoplasms; Signal Transduction

MicroRNAs (miRNAs) are post-transcriptional inhibitor regulators of gene expression that act by directly binding complementary mRNA and are key determinants of cancer initiation and progression. In this study, we revealed a role for the tumor-suppressor miRNA miR-503 in endometrioid endometrial cancer (EEC) cells. The miR-503 expression level gradually decreases across normal endometrial tissues, endometrial tissues with complex atypical hyperplasia, and EEC tissues. A relatively high level of miR-503 in EEC tissues indicates a longer survival time in EEC patients. The expression of a cell cycle-associated oncogene encoding cyclin D1 (CCND1) was inversely correlated with miR-503 expression in EEC tissues and cell lines. CCND1 has a binding sequence of miR-503 within its 3' untranslated region, and was confirmed to be a direct target of miR-503 by the fluorescent reporter assays. Increasing the miR-503 level in EEC cells suppressed cell viability, colon formation activity and cell-cycle progression, and the inhibited oncogenic phenotypes induced by miR-503 were alleviated by ectopic expression of CCND1 without the untranslated region sequence. Furthermore, in vivo studies also suggested a suppressive effect of miR-503 on EEC cell-derived xenografts. miR-503 increased in cell cycle-arrested EEC cells, and was restored to a normal level in EEC cells after cell cycle re-entry, while CCND1 displayed the opposite expression pattern. Collectively, this study suggested that miR-503 plays a tumor-suppressor role by targeting CCND1. Abnormal suppression of miR-503 leads to an increase in the CCND1 level, which may promote carcinogenesis and progression of EEC.

Topics: 3' Untranslated Regions; Aged; Animals; Carcinoma, Endometrioid; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Gene Expression Regulation, Neoplastic; Gene Transfer Techniques; Genes, Reporter; Humans; Mice; Mice, Nude; MicroRNAs; Middle Aged; Recombinant Proteins; Xenograft Model Antitumor Assays

Alteration of CyclinD1 was suggested to relate with development of endometrial carcinogenesis before, however CyclinD1 expression is not well defined in endometrial hyperplasia lesions. We checked the relationship between its expression and clinic-pathological variables of endometrial lesions to explore the possibility for CyclinD1 as a potential diagnostic and prognostic marker.. Cyclin D1 immunohistochemical analysis (IHC) was used to evaluate 201 fixed, paraffin-embedded endometrial samples which included simple hyperplasia (n = 27), atypical complex hyperplasia (ACH) (n = 41), endometrioid carcinoma (n = 103), endometrial serous carcinoma (ESC) (n = 21) and clear cell carcinoma (CCC) (n = 9). A breast cancer with known CyclinD1 expression was selected as a positive control in each immunohistochemistry run. We also performed follow-up study to estimate patients' prognosis.. CyclinD1 was significantly overexpressed in atypical complex hyperplasia (ACH), endometrioid carcinoma and clear cell carcinoma (CCC). The positive signaling of CyclinD1 was showed less than 40% in simple hyperplasia and endometrial serous carcinoma (ESC). The high expression of CyclinD1 was observed in metastasis carcinoma group more significantly than non-metastasis carcinoma group. Kaplan Meier analysis demonstrated that patients with high CyclinD1 expression had an obviously poor prognosis than patients without CyclinD1 staining (p < 0.05). Moreover, according to multivariate Cox regression analysis, CyclinD1 expression, as crucial as metastasis, was a risk marker for overall survival rate.. CyclinD1 exhibited a promising potential to predict the prognosis of patients with endometrial carcinoma. However, the statistical analysis demonstrated that CyclinD1 exhibited a poor ability to differentiate neoplastic lesions from non-neoplastic lesions; thus, the application of CyclinD1 only is not so credible for differentiation between benign and malignant lesions.. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1871063048950173.

Topics: Adenocarcinoma, Clear Cell; Adult; Biomarkers, Tumor; Biopsy; Carcinoma, Endometrioid; Chi-Square Distribution; Cyclin D1; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Middle Aged; Multivariate Analysis; Neoplasms, Cystic, Mucinous, and Serous; Prognosis; Proportional Hazards Models; Risk Factors; Time Factors; Up-Regulation

Endometrioid type adenocarcinoma sometimes occupies both endometrium and ovary and in some cases the origin cannot be determined.. In this study, we established a formula to distinguish ovarian endometrioid cancer (EOC) from endometrioid type endometrial cancer (EEC), based on our previous report of cyclin and KI67 expression pattern by immunohistochemistry of 36 EECc and 37 OECc by the logistic regression. We calculated the diagnostic accuracy using 92 test samples retrospectively and finally could diagnose the origin of 16 cases in whom endometrioid type adenocarcinoma arose in both ovary and endometrium and could be determined by Scully's criteria, and 15 cases in whom endometrioid type adenocarcinoma arose in both ovary and endometrium and Scully's criteria were not useful retrospectively.. The estimated formula is as follows: Logit(Prob(EOC))=-1.1437-0.0853 CNA+0.0423 CNB+0.173 CND1+0.0129 CNE+0.0224 CNF+0.0508 KI67, where Prob(EOC) is the probability that a clinical sample is EOC. If Prob(EOC) is larger than 0.5, the diagnosis is ovarian cancer; if less than 0.5 it is endometrial cancer. Finally, using the formula, 37 of 48 EECs (77.1%) and 33 of 44 EOCs (75.0%) were correctly classified, with an accuracy of 76.1% (p<0.0001), retrospectively. In 12 of the 16 cases (75%) who could be determined by Scully's criteria, the origin determined by Scully's criteria was concordant with the origin determined by the formula retrospectively. In the other 15 cases, 12 cases were judged as ovary/ovary, 2 cases were judged as uterus/uterus and 1 case was judged as uterus/ovary.. The formula we established was thought to be useful to distinguish the origin of the cases in whom endometrioid type adenocarcinoma arises in both ovary and endometrium.

Topics: Adult; Aged; Carcinoma, Endometrioid; Cyclin A; Cyclin B1; Cyclin D1; Cyclin E; Cyclins; Endometrial Neoplasms; Endometrium; Female; Humans; Ki-67 Antigen; Middle Aged; Ovarian Neoplasms; Retrospective Studies; Sensitivity and Specificity

Cell cycle proteins and HIF-1alpha with downstream factors are often abberrantly expressed in (pre)neoplastic tissue.. Paraffin-embedded specimens of inactive endometrium with TM (n=15), ovarian inclusion cysts (n=6), cervix with TM (tubal metaplasia) (n=3), Fallopian tubes (n=7), cycling endometrium (n=9) and a ciliated cell tumor of the ovary were stained for p16 and LhS28. 39 Endometrioid endometrial carcinomas and 5 serous endometrial carcinomas were stained for p16. Additionally, inactive endometrium (n=15) was immunohistochemically stained for p21, p27, p53, cyclin A, cyclin D1, cyclin E, HIF-1alpha, CAIX, Glut-1 and MIB-1.. A mosaic pattern of expression of p16 was seen throughout in all cases of endometrial TM (15/15), in 2/6 of the ovarian inclusion cysts with TM, in all (3/3) cervical TM and focal in 5/7 of Fallopian tube cases. Mosaic expression was also seen in a ciliated cell tumor of the ovary and in 18/39 of endometrioid endometrial carcinomas, and diffuse p16 expression was seen in 5/5 serous carcinomas. In comparison with normal endometrium, TM areas in the endometrium showed significantly increased expression of HIF-1alpha, cyclin E, p21 and cyclin A, and decreased expression of p27. Membranous expression of CAIX and Glut-1 was only seen in TM areas, pointing to functional HIF-1alpha.. As p16 is consistently expressed in TM, less and only patchy expressed in the normal Fallopian tube, is paralleled by aberrant expression of cell cycle proteins, HIF-1alpha, CAIX and Glut-1 and resembles the pattern of p16 expression frequently seen in endometrial carcinomas, we propose endometrial TM to be a potential premalignant endometrial lesion.

Topics: Carcinoma, Endometrioid; Cervix Uteri; Cyclin A; Cyclin D1; Cyclin E; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Endometrial Neoplasms; Endometrium; Fallopian Tubes; Female; Glucose Transporter Type 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Metaplasia

We have recently described RUNX1/AML1 up-regulation in endometrioid endometrial carcinoma (EEC), proposing that it could play a role during the initial steps of myometrial infiltration. Some cell cycle regulators, including the cyclin-dependent kinase inhibitor p21WAF1/CIP1, have been described as targets of RUNX1/AML1. In this study, we have attempted to address the question of whether RUNX1/AML1, acting both as a gene transcription activator and a repressor, depending on the context, can be correlated with the expression of p21WAF1/CIP1 in gynecologic malignancies, in particular in EEC, where the role of p21(WAF1/CIP1) remains controversial. Toward this end, we analyzed p21WAF1/CIP1 expression in a large panel of EEC samples using real-time quantitative polymerase chain reaction and tissue microarray immunohistochemistry, and evaluated the extent to which RUNX1/AML1 and p21WAF1/CIP1 interacted in the EEC samples. The strong correlation found between RUNX1/AML1 and p21WAF1/CIP1 suggested cooperation between the 2 genes in EEC, especially in those tumor samples corresponding to stage IC carcinomas, infiltrating more than 50% of the myometrium. We hypothesize that p21WAF1/CIP1 and RUNX1/AML1 interact during the initial steps of tumor dissemination in EEC, and we discuss mechanisms that could underlie myometrial infiltration and/or the promotion of an invasive phenotype.

Topics: Biomarkers, Tumor; Carcinoma, Endometrioid; Core Binding Factor Alpha 2 Subunit; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Endometrial Neoplasms; Female; Humans; Myometrium; Neoplasm Invasiveness; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Tissue Array Analysis; Tumor Suppressor Protein p53; Up-Regulation

We investigated cyclin D1 expression in proliferative endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, and examined the correlation of cyclin D1 expression with Ki67 as a cell proliferation associated marker. Immunohistochemical expression of cyclin D1 and Ki67 were studied in 30 cases with endometrial carcinoma, 14 cases with atypical hyperplasia, 15 cases with simple hyperplasia and 30 cases with proliferative endometrium.. One out of 30 patients (3.3%) with proliferative endometrium, 1 out of 14 patients (7.1%) with atypical hyperplasia, and 8 out of 30 patients (26.6%) with endometrial carcinoma were found to have immunoreactivity to cyclin D1. All cases of simple hyperplasia had negative staining for cyclin D1. A positive immunoreaction for Ki67 was obtained in all cases. Statistically significant difference was found in cyclin D1 immunoreactivity between both proliferative endometrium and adenocarcinoma, and simple hyperplasia and adenocarcinoma (p<0.05). In patients with adenocarcinoma, cyclin D1 immunoreactive cases had higher mean Ki67 values compared with the non-immunoreactive ones (p<0.05). Ki67 and cyclin D1 immunoreactivity had no impact on overall survival. Univariate analysis revealed a significant relationship between survival and grade and stage (p<0.01). Cyclin D1 expression was not correlated with age, depth of myometrial invasion, lymphovascular space involvement, grade, lymph node metastasis and stage.. Cyclin D1 expression in endometrial carcinoma is higher than proliferative endometrium and simple hyperplasia. These findings support that cyclin D1 may play a role in endometrial carcinogenesis.

Topics: Biomarkers; Carcinoma, Endometrioid; Cell Proliferation; Cyclin D1; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Ki-67 Antigen; Middle Aged

PTEN is a tumor suppressor gene that inhibits cell proliferation by regulating intracellular signaling pathways, and this activity can be abolished by mutations of the PTEN gene. This study was designed to examine the correlation of PTEN expression with the expression of cell cycle regulators and with clinicopathological parameters in endometrioid adenocarcinoma of the uterine corpus.. Tissue samples of 117 endometrioid adenocarcinomas in addition to those of 19 normal endometria and 20 endometrial hyperplasias were used for the study. Immunohistochemical staining for PTEN protein was performed with the labeled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue samples. PTEN expression was represented as the staining score.. Immunohistochemistry showed that the nuclei of cells were positive for PTEN. The PTEN staining score of normal endometrium was significantly higher in the proliferative phase than in the secretory phase. The scores of various endometrial hyperplasias were not significantly different from each other, regardless of the type of hyperplasia. The PTEN staining scores of endometrioid adenocarcinomas were 7.6+/-5.2 in G1, 9.6+/-5.2 in G2, and 11.9+/-3.7 in G3, and increased significantly as the histological grade increased. PTEN staining score was not significantly correlated with clinicopathological parameters such as FIGO stage, myometrial invasion, lymph-vascular space invasion (LVSI), lymph node metastasis or group, but was significantly correlated with labeling indices (LIs) of cell cycle regulators such as Ki-67, cdk2, cyclin A, cyclin D1, cyclin E, p27, and p53. The PTEN staining score of p53-wild cases was significantly lower than that of p53-mutant ones, but there was no significant difference of the score in cases with different PTEN gene status. PTEN expression was significantly lower in cases with both high levels of estrogen receptor and progesterone receptor.. PTEN protein expression was decreased in well-differentiated and less growth-aggressive endometrial carcinoma with wild-type p53 gene and high levels of ER and PR. This suggests that disturbed PTEN expression occurs in an early phase of the tumorigenesis of well-differentiated endometrial carcinoma.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Endometrioid; CDC2-CDC28 Kinases; Cell Cycle Proteins; Cell Differentiation; Cyclin A; Cyclin D1; Cyclin E; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p27; Endometrial Hyperplasia; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Ki-67 Antigen; Lymph Nodes; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Staging; Phosphoric Monoester Hydrolases; PTEN Phosphohydrolase; Receptors, Estrogen; Receptors, Progesterone; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Uterine Neoplasms

Malignant transformation of endometriosis, an uncommon phenomenon, can occur in gonadal and extragonadal sites and results in a wide histological range of tumors. Published series reporting malignant transformation of endometriosis have largely been confined to clinical and histopathological discussions with no studies reporting oncoprotein expression and genetic alterations. We report three cases of carcinomas arising in ovarian endometriosis: a serous cystadenocarcinoma, an endometrioid carcinoma with squamous differentiation, and a pure squamous cell carcinoma. Each tumor was analyzed immunohistochemically to compare oncoprotein expression (p53, bcl2, cyclin D1, and c-erb B2) between the tumors and the endometriotic tissue as well as with comparative genomic hybridization (CGH) to compare genetic alterations. All three tumors expressed nuclear p53, in contrast to the endometriotic tissue in which no p53 expression was found. Both endometrial and tumor tissue expressed bcl-2. No expression of cyclin D1 or c-erb B2 was detected in endometriotic or tumoral tissues. The CGH analysis revealed one or two chromosomal aberrations in each of the three tumors with gains on chromosomes 1q, 8q, and 13q, and losses on chromosome 10p. The endometriotic tissue, as expected, showed a normal genetic profile. These results suggest that p53 protein abnormalities and chromosomal aberrations may be involved in malignant transformation of endometriosis in the ovary. However, our results are limited by the number of cases examined and a definite conclusion on the pathogenesis of this process should be followed by future studies with a larger number of cases.

Topics: Adult; Carcinoma, Endometrioid; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chromosome Aberrations; Cyclin D1; Cystadenocarcinoma, Serous; DNA; Endometriosis; Female; Humans; Immunohistochemistry; Middle Aged; Nucleic Acid Hybridization; Ovarian Diseases; Ovarian Neoplasms; Receptor, ErbB-2; Tumor Suppressor Protein p53

Endometrioid carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen appears to be involved in the development of endometrioid carcinoma. Other mechanisms of endometrial carcinogenesis include mutations in p53 and PTEN tumor suppressor genes and overexpression of cyclin D1. However, the pattern of cyclin D1 expression is not well defined in normal, hyperplastic, neoplastic, and metaplastic endometrium.. Cyclin D1 immunohistochemical analysis was used to evaluate 108 fixed, paraffin-embedded endometrial biopsy specimens and uterine resections obtained from 108 patients. Specimens included proliferative and secretory endometria, simple and complex hyperplastic lesions, and endometrioid adenocarcinoma. Normal and metaplastic surface epithelia were also evaluated independently of glandular morphologic features.. Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrioid adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. Significant overexpression was also noted in papillary, syncytial, and squamous metaplasias compared with normal surface epithelium or epithelium with tubal metaplasia.. Overexpression of cyclin D1 increases from normal endometrium to hyperplasia and carcinoma, suggesting that it may play a role in endometrial carcinogenesis. Overexpression of cyclin D1 in endometrial glands was independent from overexpression of cyclin D1 in surface metaplastic epithelium.

Topics: Carcinoma, Endometrioid; Cell Nucleus; Cyclin D1; Endometrial Neoplasms; Endometrium; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Metaplasia; Precancerous Conditions

COX-2, the isoform of cyclooxygenase inducible by cytokines, mitogens, and growth factors, appears to play an important role in inflammation and carcinogenesis. In the colon, COX-2 overexpression results in cell cycle alterations, and NSAIDs have proven effective in cancer chemoprevention. HNPCC (hereditary nonpolyposis colon cancer) is a clinically defined cancer susceptibility syndrome in which women are also at significantly increased risk for the development of endometrial carcinoma. The purpose of this study was to evaluate expression of COX-2 in benign and malignant endometrium in the context of other cell cycle and proliferation markers, including Ki-67, cyclin D1, and the cyclin-dependent kinase inhibitor, p21. Immunostains with COX-2, Ki-67, cyclin D1, and p21 antibodies were performed on formalin-fixed and paraffin-embedded tissue sections from 40 cases: 10 benign (5 atrophic and 5 proliferative) endometria, 6 hyperplasias (complex without atypia), and 24 endometrioid carcinomas (9 well, 4 moderately, and 11 poorly differentiated). Ki-67 was positive in all proliferative and neoplastic endometria. Cyclin D1 and p21 were both overexpressed in endometrial hyperplasia and endometrioid carcinomas. COX-2 was negative in the nonneoplastic endometrium, stained minimally in the well-differentiated endometrioid carcinomas, and stained most strongly in the moderately and poorly differentiated endometrioid carcinomas. Because cyclin D1 may function as an oncogene, its effects may dominate the usual inhibitory effect of a rising p21. Alternatively, it has been shown that p21 can promote cell cycle function by stabilizing cell cycle complexes. The overexpression of COX-2 in poorly differentiated endometrioid carcinoma and lack of expression in hyperplasia and well-differentiated carcinoma suggests that in this form of cancer, COX-2 may play a role in tumor progression rather than tumor initiation.

Topics: Biomarkers, Tumor; Carcinoma, Endometrioid; Cell Cycle; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Cyclooxygenase 2; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Isoenzymes; Ki-67 Antigen; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Retrospective Studies