Lymphangiogenesis of normal endometrium and endometrial adenocarcinoma

BACKGROUND: Information about lymphatics and lymphangiogenesis in the human endometrium is limited. We investigated the distribution of endometrial lymphatic vessels during the normal menstrual cycle and in association with endometrial adenocarcinoma and investigated the expression of lymphangiogenic growth factors, vascular endothelial growth factor (VEGF)-C, VEGF-D and VEGF receptor-3 (VEGF-R3). METHODS AND RESULTS: Full thickness uterine samples (n = 23 proliferative; n = 23 secretory) and endometrial adenocarcinoma samples (n = 7 grade I; n = 10 grade III) were collected for the study and analysed by immunohistochemistry and western blotting. Lymphatic vessels of the functionalis were significantly reduced compared with basalis (P = 0.001) across the menstrual cycle with lymphatics of the basalis sometimes intimately associated with spiral arterioles. Lymphatic vessels of endometrial adenocarcinomas were located intra-tumoural and peri-tumoural with significant increases in the peri-tumoural lymphatic vessels compared with normal basalis (P = 0.02). Interestingly, high-grade adenocarcinoma vessels containing tumour emboli demonstrated a mixed blood/lymphatic endothelial cell phenotype. VEGF-C and VEGF-D were immunolocalized in glandular epithelium and some stromal cells with the staining intensity of this localization increasing in endometrial adenocarcinoma. Protein analysis identified VEGF-C (58, 41, 31 and 21 kD) and VEGF-D (56, 41, 31 and 21 kD) and VEGF-R3 (148 and 65 kD) peptides in normal endometrium, with significant increases in several of these peptides for VEGF-C and VEGF-D and no changes in protein expression for VEGF-R3 in endometrial adenocarcinoma. CONCLUSION: Endometrial lymphatics are significantly reduced in the functionalis, and increases in endometrial adenocarcinoma peri-tumoural lymphatics are associated with increases in VEGF-C and VEGF-D peptides.     

Adrenomedullin, Bcl-2 and microvessel density in normal, hyperplastic and neoplastic endometrium

Adrenomedullin (ADM) is a multifunctional 52-amino acid peptide involved in numerous physiological and pathological processes, including angiogenesis, growth regulation, differentiation, and vasodilation. ADM is thought to act through the G protein-coupled receptor calcitonin receptor-like receptor, with specificity being conferred by receptor-associated modifying protein 2. The aim of the present study was to clarify the roles of ADM status, and tumor vessels in endometrium. Specimens were examined for ADM, microvessel density (MVD), area of venules (AV) and Bcl-2 oncoprotein using an immunoperoxidase method. The difference of ADM between normal proliferative phase and hyperplasia without atypia was significant ( P < 0.05). The level of Bcl-2 was significantly different between hyperplasia without atypia and hyperplasia with atypia ( P < 0.05). ADM, MVD and AV in the endometrium increased in a stepwise manner from normal, simple or complex hyperplasia with or without atypia to grade 1 adenocarcinoma. In contrast, expression of Bcl-2 oncoprotein was decreased. These parameters identify the role of ADM expression and Bcl-2 protein in relation to cell growth and vasodilating in the neoplastic changes.     

Patterns of reactivity with the monoclonal antibodies HMFG1 and HMFG2 in normal endometrium, endometrial hyperplasia and adenocarcinoma

Using an indirect immunoperoxidase technique the expression of the epitopes in human milk fat globule (HMFG) membranes detected by the monoclonal antibodies HMFG1 and HMFG2 was studied in the normal endometrium and in cases of cystic glandular hyperplasia, glandular hyperplasia with architectural atypia (complex hyperplasia), glandular hyperplasia with cytological atypia (atypical hyperplasia) and invasive adenocarcinoma. Luminal reactivity with HMFG1 was seen in cases of normal endometrium, cystic glandular hyperplasia and glandular hyperplasia with architectural atypia. In contrast most cases of glandular hyperplasia with cytological atypia and invasive adenocarcinoma also showed areas of cytoplasmic reactivity. Reactivity with HMFG2 was scanty.     

Caspase cascade of Fas-mediated apoptosis in human normal endometrium and endometrial carcinoma cells

Human endometrial epithelial cells undergo apoptosis immediately before the menstrual period. Apoptotic signalling was analysed using human endometrial tissue and a human endometrial carcinoma cell line (HHUA). Activity levels of caspase-3, -8, and -9 were elevated in human endometrium during the late secretory phase and in HHUA cells incubated with an anti-Fas monoclonal antibody (mAb). Fas-mediated apoptosis of HHUA cells was blocked by prior exposure to inhibitors of caspase-9, -8 and -3. In HHUA cells treated with anti-Fas mAb, a release of cytochrome c was detected in the cytosolic fraction, in addition a full-length Bid was degraded. Full-length FLIP(L) (p55) was degraded during apoptosis, and p29 (regarded as the product of p55 cleavage) appeared instead of FLIP(L). In normal human endometrial tissue, Bid degradation was also observed in a cyclic manner with a peak during the early secretory phase of the menstrual cycle. Furthermore, the release of cytochrome c was seen in the early secretory phase. However, expression of FLIP(S) was only observed during the menstrual cycle in normal endometrial tissue. We concluded that the main apoptotic signalling in both normal human endometrial tissue and HHUA cells exposed to anti-Fas mAb is the mitochondrial pathway via Bid degradation. Although the function of FLIP is still unknown on normal endometrial tissue, it may be regulated by FLIP(L) expression on HHUA cells derived from human endometrial carcinoma.     

A sertoliform endometrioid adenocarcinoma of the endometrium

Sertoliform endometrioid adenocarcinomas of the ovary are well recognized but, curiously, a sertoliform pattern has not previously been noted in endometrioid adenocarcinomas of the endometrium. An endometrial tumour is described which showed in some areas the typical appearances of an endometrioid adenocarcinoma and in others a pattern closely resembling that of a Sertoli cell tumour.     

Liquid-based endometrial cytology in the management of sonographically thickened endometrium

Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures.     

Mucinous endometrial adenocarcinoma simulating microglandular hyperplasia of the cervix

A case of endometrial adenocarcinoma simulating microglandular hyperplasia (MGH) of the cervix is presented. A postmenopausal 53-year-old woman, with no previous history of taking exogenous hormones, presented with vaginal bleeding. An endometrial biopsy exhibited a tumor composed predominantly of a microglandular proliferation of tightly packed glands with mild to moderate atypia and mitotic figures. The majority of the tumor cells contained intracytoplasmic mucin. There were numerous neutrophils within the microglandular lumens and in the stroma. The tumor was focally positive for carcinoembryonic antigen and vimentin. The MGH-like proliferation, focally, had a transition to a conventional mucinous adenocarcinoma. Hysterectomy specimens showed a residual mucinous endometrial adenocarcinoma with no myometrial invasion, the uterine cervix was unremarkable. Four years following her hysterectomy the patient was well, with no evidence of disease. Pathologists need to be cautious about MGH-like changes in the endometrial biopsy of postmenopausal women and be aware of this type of endometrial cancer as it may be misdiagnosed.     

Angiogenic co-operation of VEGF and stromal cell TP in endometrial carcinomas

Vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) are important angiogenic enzymes, inducing new blood vessel formation in many human malignancies. In this study, the immunohistochemical expression of the two molecules was analysed in a series of 121 endometrial carcinomas. VEGF was expressed exclusively in cancer cells, while TP expression was shown in cancer cells (TPcc) and in stromal cells (TPsc) of both fibroblastic and myometrial origin. In all cases, enzymatic detection was particularly evident at the invading tumour front. At this site, TPsc, but not VEGF, expression was associated with non-endometrioid-type carcinomas, high tumour grade, deep myometrial invasion, and advanced stage. VEGF, but not TP, expression was related to increased angiogenesis (p=0.01). Double stratification of the two factors, however, marked VEGF/TPsc co-expression as the most potent angiogenic phenotype (p=0.008), suggesting a synergistic function. Survival analysis revealed that VEGF and TPsc, whether expressed alone or in combination, define poor prognosis. In multivariate analysis, however, stage of disease (p<0.0001, t-ratio 4.4) and VEGF expression (p=0.01, t-ratio 2.4) were the most important prognostic variables. Furthermore, VEGF expression emerged as the only independent prognostic variable in stage I endometrial carcinomas (p=0.04, t-ratio 1.9). This was not shown for TP, probably because of its close association with histopathological parameters. In conclusion, VEGF is a major angiogenic factor in endometrial carcinomas and an independent prognostic factor in stage I endometrial disease. TP is not an effective contributor to the angiogenic process, but is associated with aggressive histological features. The two factors, when co-expressed, play a co-operative role in the induction of angiogenesis.     

Clinical significance of histiocytes in the detection of endometrial adenocarcinoma and hyperplasia

The purpose of this case-control study was to determine the clinical significance of histiocytes and normal endometrial cells as cytologic markers of adenocarcinoma or hyperplasia of the endometrium. Cervical-vaginal smears obtained in 102 patients with mean age 59.7 yr with abnormal uterine bleeding and endometrial pathology, and 101 controls with mean age 56.5 yr with postmenopausal bleeding and whose cytologic smear was negative, were evaluated. Histiocytes alone failed to predict either endometrial adenocarcinoma (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.32–3.22) or hyperplasia (OR, 1.10; 95% CI, 0.37–3.30). The odds of endometrial carcinoma in symptomatic, postmenopausal women was three times greater in the presence of histiocytes with phagocytosis of acute inflammatory cells (PIC) (OR, 3.00; 95% CI, 1.16–7.70). Endometrial hyperplasia was more frequently observed when cervical smears contained normal endometrial cells (OR, 4.09; 95% CI, 1.14–14.67). Only histiocytes with PIC and normal endometrial cells carry a three- and fourfold greater likelihood of coexistent endometrial adenocarcinoma and hyperplasia, respectively. Such strong association may require endometrial biopsy or transvaginal ultrasonography to uncover lesional tissue in the endometrial cavity. Diagn. Cytopathol. 1998;19:89–93. © 1998 Wiley-Liss, Inc.     

Long-term conservative therapy for endometrial adenocarcinoma in young women

BACKGROUND: To evaluate the efficacy and safety of long-term conservative therapy with medroxyprogesterone acetate (MPA) for endometrial carcinoma in young patients who had experienced failure after initial therapy or relapse, we reviewed the clinical and pathologic records of eight patients diagnosed with well-differentiated endometrial adenocarcinoma without myometrial invasion who were treated with MPA for over 6 months because of treatment failure or relapse. RESULTS: The average duration of MPA treatment was 22 months. All patients were followed-up for a mean of 76.5 months. Seven patients responded to initial MPA treatment within a period of 14 months (mean, 7.9 months). All these patients experienced relapse and the mean time to relapse was 11.6 months (range, 4-33 months). All six patients with relapse were treated with additional treatments of MPA, and all but one responded to this treatment within a period of 16 months (mean, 8.0 months). Six patients ultimately underwent hysterectomy. All presented well-differentiated endometrioid adenocarcinomas without extrauterine disease. Three became pregnant and two delivered full-term normal infants. No patient died of the disease. CONCLUSION: Although lesions are expected to disappear with prolonged MPA treatment, this form of progestin therapy is hazardous because recurrence occurs frequently. Only strictly selected patients should therefore be indicated for long-term MPA treatment and careful evaluation before and after treatment should be performed.     

Nuclear features in endometrial cytology: Comparison of endometrial glandular and stromal breakdown and endometrioid adenocarcinoma grade 1

This study was to clarify the nuclear features of “condensed clusters of stromal cells (EGBD‐stromal cells)” and “metaplastic clumps with irregular protrusions (EGBD‐metaplastic cells)” which may be recognized in endometrial glandular and stromal breakdown (EGBD) cases in liquid‐based cytologic (LBC) preparations of endometrial brushings. The material consists of cytologic smears of 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade 1 (G1) for which histopathological diagnosis was obtained by endometrial curettage. Nuclear findings were examined in PE cells, EGBD‐stromal cells, EGBD‐metaplastic cells, and G1 cells, respectively. It was examined about the following items: (1) Nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) An area of cell nuclei; (4) Overlapping nuclei; (5) The distribution pattern of nuclei within cell clusters. The following observations were made: (1) In PE cells, round‐oval nuclei appeared to predominate, overlapping nuclei were not observed, and a slightly abnormal distribution pattern of nuclei was recorded; (2) In EGBD‐stromal cells, reniform nuclei were characteristically observed, nuclei had small size and a generally elongated appearance, overlapping nuclei were recognized, and a remarkable abnormal distribution pattern of nuclei was found; (3) In EGBD‐metaplastic cells, spindle nuclei were a characteristic feature, nuclei were larger in size and had a bipolar appearance, overlapping nuclei with moderately abnormal distribution pattern of nuclei were identified; (4) In G1 cells round‐oval nuclei predominated, overlapping nuclei with moderately abnormal distribution pattern of nuclei were found. The study demonstrates that the analysis of selected nuclear findings appears to be very useful in the cytopathological assessment of endometrial lesions in LBC samples, especially for the discrimination of EGBD and G1. Diagn. Cytopathol. 2012. © 2012 Wiley Periodicals, Inc.     

Association between the apoptotic index and established prognostic parameters in endometrial adenocarcinoma

The aim of this study was to determine if the apoptotic index can be readily determined for endometrial carcinoma in hysterectomy specimens and to establish if any association exists between the apoptotic index and tumour grade and stage. The apoptotic index, defined as the percentage of morphologically identified apoptotic cells and apoptotic bodies in 3000 tumour cells, was calculated for 15 adenocarcinomas of the endometrium. An association between apoptotic index and tumour grade and stage was sought. Two grade 3 adenocarcinomas of endometrium had a higher apoptotic index (5.15% to 6.43%) than 13 grade 1 and 2 lesions (1.18% to 3.8%) and formed a distinct group in this series. No association between apoptotic index and tumour stage was demonstrable. Apoptotic index can be readily estimated in routine hysterectomy specimens for endometrial adenocarcinoma. A high apoptotic index shows an association with features normally correlated with a poor clinical outcome although its value as an independent prognostic index has yet to be established.     

Expression of immunoreactivity of nuclear findings by p53 and cyclin a in endometrial cytology: Comparison with endometrial glandular and stromal breakdown and endometrioid adenocarcinoma grade 1

It is well known that “condensed cluster of stromal cells (CCSC)” and “metaplastic clumps with irregular protrusion (MCIP)” in endometrial glandular and stromal breakdown (EGBD) cases may simulate “clumps of cancer cells (CCC)” in endometrioid adenocarcinoma grade 1 (G1), leading to difficulty in cytological interpretation. The aim of this study was undertaken to clarify the cytological immunoreactivity of nuclear findings about CCSC and MCIP which may be recognized in EGBD cases by using p53 protein and cyclin A in liquid‐based cytologic (LBC) preparations. The material consists of cytologic smears of 20 cases of EGBD and 20 cases of G1 for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. The evaluation of immunoreactivity was performed by using the intensity of nuclear staining and the nuclear labeling index (N‐LI). The intensity of nuclear staining was scored as negative (0), weak (1), moderate (2), or strong (3). The N‐LI was scored as less than 10% (0), from 10 to 25% (1), from 26 to 50% (2), or greater than 50% (3). The final score was calculated of the addition of both partial scores. Results are as follows: As for the p53 protein immunoreactivity, CCC (2.4 ± 1.4) was a significantly higher value in comparison with CCSC (0) and MCIP (0.8 ± 0.4), respectively. As for the cyclin A immunoreactivity, CCC (2.8 ± 1.1) was a significantly higher value in comparison with CCSC (0) and MCIP (0.6 ± 0.5), respectively. CCSC and MCIP in EGBD are misunderstood as cellular atypia and structural atypia on occasion; but, as for results of the immunoreactivity scores of p53 protein and cyclin A in our study, it seemed that those biochemical characters proved that the biological activity level was low (or degenerative). The results of the current study demonstrated that the cytological immunoreactivity of nuclear findings by p53 and cyclin A appear to be more useful for the LBC assessment of endometrial lesions, especially for the discrimination of EGBD and G1.Diagn. Cytopathol. 2013;41:303–307. © 2011 Wiley Periodicals, Inc.     

High frequency of RASSF1A and RARb2 gene promoter methylation in morphologically normal endometrium adjacent to endometrioid adenocarcinoma

Aims: To identify a DNA methylation signature of endometrioid carcinoma of the endometrium (EEC) in the early stages of endometrial carcinogenesis. Methods and results: Archival biopsy specimens of 39 EECs, 14 cases of atypical hyperplasia (AH), 11 histologically normal endometrial tissues adjacent to EECs and 24 normal control endometrial samples were retrieved. The cases were tested by quantitative methylation‐specific polymerase chain reaction with primers hybridizing in the promoter regions of five genes frequently methylated in human cancer (RASSF1A, RARb2, P16, MGMT and GSTPi). Twenty‐nine of 39 (74%) EECs and 7/14 (50%) AHs were methylated for the RASSF1A gene, whereas 17/39 (44%) EECs and 6/14 (43%) AHs were positive for the methylation of the RARb2 gene. No significant results were obtained for the other genes (P16, MGMT and GSTPi). Interestingly, 4/11 (36%) and 6/11 (55%) histologically normal endometrial tissues adjacent to EEC showed, respectively, RASSF1A and RARb2 gene methylation. Furthermore, these 11 specimens were microsatellite stable and showed similar proliferative, cell cycle and apoptotic mean labelling indices as the normal endometrial control tissues. Conclusions: Promoter region methylation of RASSF1A and RARb2 genes is an early event in endometrial carcinogenesis.     

Uterus and endometrium: Inhibition of human endometrial stromal cell proliferation by interleukin 6

We investigated the ability of interleukin 6 (IL-6) to modulatehuman endometrial stromal cell growth in vitro Stromal cellproliferation in response to treatment with varying concentrationsof IL-6 was determined. Endometrial tissue was obtained from10 normally cycling women during the secretory phase of theirmenstrual cycle. Treatment with IL-6 resulted in a dose- andcell-density-dependent inhibition of endometrial stromal cellproliferation in vitro. The maximal inhibition was observedwith 200 pg/ml of IL-6 and at a concentration of 10⁵ cells/well.During in-vitro culture, stromal cells produced low amountsof IL-6 and demonstrated the presence of IL-6 receptor. Thesedata demonstrate that IL-6 acts as a growth-regulatory signalfor human endometrial stromal cells. We postulate that IL-6may contribute to the maintenance of homeostasis in normal endometriumand that perturbation of IL-6 mediated responses may play arole in disorders of the endometrium such as endometrial cancerand endometriosis.     

子宫颈腺癌与子宫内膜腺癌的组化及免疫组化观察

目的：探讨组化染色及免疫组化在宫颈腺癌与宫内膜腺癌诊断价值及临床意义。方法：采用组化染色及免疫组化Ｓ－Ｐ方法对宫颈腺癌及宫内膜腺癌的粘蛋白含量、分布及免疫组化阳性物的表达进行观察。结果：宫颈腺癌以含丰富的唾液酸粘蛋白为主，而子宫内膜腺癌以硫酸粘蛋白为主。波形蛋白（ｖｉｍｅｎｔｉｎ）在宫内膜腺癌阳性表达率６８．９％，而宫颈腺癌大多呈阴性表达，雌激素受体（ＥＲ）表达在宫内膜腺癌达６０．９％，而宫颈腺癌仅１９．６％，两者均差异有显著性（Ｐ＜０．０５）。而抑癌基因ｐ５３和癌基因ｃ－ｅｒｂＢ－２阳性率与癌肿的分级和预后有关。结果：粘蛋白组化染色及ｖｉｍｅｎｔｉｎ可帮助鉴别诊断宫颈腺癌及宫内膜腺癌，而ＥＲ、ｐ５３、ｃ－ｅｒｂＢ－２对病人的预后有一定意义     

人子宫内膜腺癌细胞的超微结构研究王自能

目的：研究人子宫内膜腺癌细胞的超微结构。方法：利用透射电镜观察１２例人子宫内膜腺癌组织。结果：人子宫内膜腺癌的癌细胞具有圆形、长形、不规则形及亮、暗等５种不同形态。圆形癌细胞通常与腺腔相邻或脱落于腺腔内。长形癌细胞，除细胞器较少及细胞核明显增大外，其形态与妊娠中期人胎儿子宫内膜及月经周期增生早期的子宫内膜的腺上皮细胞相似。外形不规则的癌细胞其细胞核呈分叶状，常见于侵入基质的癌团。亮癌细胞缺乏细胞器，可能是幼稚癌细胞。暗癌细胞呈现核胞质浓缩及染色质边聚，是细胞凋亡的一种现象。此外，尚可见癌细胞出现细胞凋亡和凋亡小体被相邻癌细胞吞噬及个别癌细胞胞质内有电子致密度不同的红细胞。结论：人子宫内膜腺癌有５种类型细胞组成，癌细胞的凋亡是抑制肿瘤生长的方式之一，且癌细胞可以吞噬和消化受损的红细胞。     

子宫内膜腺癌组织中cyclinD1、PCNA和Ki-67的表达

目的　探讨cyclinD1、PCNA和Ki 6 7在子宫内膜腺癌组织中的表达及其意义。 方法　采用免疫组化S P法检测正常增生期子宫内膜 10例、单纯性增生 30例、复杂性增生 30例、非典型增生 30例和子宫内膜腺癌 4 7例组织中cyclinD1、PCNA和Ki 6 7的表达。结果　cyclinD1在增生期子宫内膜组织中未见阳性表达 ,在单纯性增生、复杂性增生、非典型增生和子宫内膜腺癌组织中的阳性表达率分别为 13 3%、16 7%、30 0 %和 5 7 8%。非典型增生和子宫内膜腺癌组织阳性表达率高于增生期宫内膜、单纯性和复杂性增生 (P <0 0 5 ) ,cyclinD1蛋白表达与子宫内膜腺癌临床分期、肌层浸润和淋巴结转移呈正相关 (P<0 0 5 ) ,而与肿瘤的分化程度无关 (P >0 0 5 )。PCNA和Ki 6 7在非典型增生组标记指数 (LI)高于增生期宫内膜、单纯性和复杂性增生组 ,子宫内膜腺癌组高于非典型增生组 (P <0 0 5 ) ,PCNA和Ki 6 7LI与肿瘤的分化程度、临床分期、肌层浸润和淋巴结转移呈正相关 (P <0 0 5 )。PCNA和Ki 6 7在cyclinD1阳性表达组的LI高于阴性组 (P <0 0 5 )。结论　cyclinD1蛋白过度表达可能在子宫内膜癌的发生、发展中起重要作用 ,其作用途径可能是通过促进细胞增殖而实现的。     

转移抑制基因KAI1表达与子宫内膜腺癌进展的关系

目的探讨KAI1蛋白表达与子宫内膜腺癌进展的关系。方法应用免疫组化SP法检测20例正常子宫内膜组织、17例子宫内膜不典型增生和48例子宫内膜腺癌组织中KAI1蛋白的表达情况。结果子宫内膜腺癌中KAI1蛋白的阳性率明显低于正常内膜组织(P<0.01)和内膜不典型增生组织(P<0.01)。KAI1蛋白的表达随子宫内膜腺癌恶性程度(P<0.01),肌层浸润深度(P<0.01)及手术-病理分期(P<0.05)的增高而降低,并与子宫内膜腺癌组织学类型有关(P<0.01),有淋巴结转移的组织中KAI1蛋白阳性率明显低于无转移组织(P<0.01)。KAI1阴性的患者总的生存率低于阳性者(P<0.01,<0.01)。结论KAI1蛋白在子宫内膜腺癌的恶性进展中表达下调,有望成为内膜癌恶性程度评估,转移预测和判断预后的有效指标。