人子宫内膜腺癌细胞的超微结构研究

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例仓宫内膜腺癌组织。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中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     

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。     

腹壁异位子宫内膜恶变为透明细胞腺癌临床病理特征及鉴别诊断

目的 探讨腹壁异位子宫内膜恶变为透明细胞腺癌临床病理特点、诊断及鉴别诊断.方法 对1例腹壁异位子宫内膜恶变为透明细胞腺癌的临床及病理资料进行分析,并复习相关文献.结果 腹壁异位子宫内膜恶变为透明细胞腺癌的形态,与发生在子宫内膜和卵巢等部位的形态学改变相似.肿瘤细胞呈巢状实性或腺样排列,实性区域胞质透亮,伴广泛凝固性坏死.腺样区域腺体拉长及相互连接形成隧道样结构,肿瘤细胞呈鞋钉状,胞质嗜酸性,核大突向腺腔.免疫表型:CK7、CK、CEA(多克隆)、EMA和vimentin均阳性;ER灶性阳性.CEA(单克隆)、PR、CK20、MC、CR、S-100、CK5/6和Moc31均阴性.结论 腹壁异位子宫内膜恶变为透明细胞腺癌非常少见,免疫表型无特异性,确诊主要依靠病史及HE形态特点.需与汗腺来源的腺癌、转移性腺癌和恶性上皮型间皮瘤进行鉴别.     

子宫内膜间质肉瘤和低分化子宫内膜样腺癌SMA、Desmin、ER、P53的病理分析对比

目的 探讨子宫内膜间质肉瘤和低分化子宫内膜样腺癌临床病理特征,以期提高鉴别和诊断的准确性.方法 回顾性分析2015年1月至2017年1月我院收治的30例子宫内膜间质肉瘤,以及30例低分化子宫内膜样腺癌患者,分别从巨检、镜检、免疫组化三方面进行病理分析与总结.结果 巨检结果发现,子宫内膜间质肉瘤肿块切面多数表现为灰白色,并且未发现明显细胞坏死现象.低分化子宫内膜样腺癌表面内膜粗糙、质脆,可见明显溃疡、出血坏死或肌层浸润现象.镜检结果发现,子宫内膜间质肉瘤呈现不规则舌状现象、肿瘤细胞排列密集,无核分裂或者核分裂不明显,血管周围肿瘤细胞呈现同心圆样排列.低分化子宫内膜样腺癌的腺体呈现多腺管状,腺体排列不规则,大小不一致,腺上皮细胞增生出现排列紊乱,并且增生细胞出现堆积现象,核分裂明显.免疫组化结果发现,低分化子宫内膜样腺癌ER表达阳性率高于子宫内膜间质肉瘤ER表达阳性率(100.00％＞ 66.67％),差异有统计学意义(P＜0.05).两组患者SMA、Desmin、P53表达阳性率之间无明显差别,差异无统计学意义(P＞0.05).结论 子宫内膜问质肉瘤和低分化子宫内膜样腺癌在巨检、镜检和免疫组化上可予区分.     

女性大网膜腺癌2临床病理分析

目的 探讨女性大网膜腺癌临床病理特征、诊断与鉴别诊断.方法 对2例大网膜腺癌进行形态学观察及免疫组化研究,并结合文献与卵巢原发癌对比分析.结果 大网膜腺癌组织学特征:例1由复层非黏液性柱状上皮细胞构成,细胞排列成圆形或卵圆形腺样结构,部分腺体融合呈筛网状,诊断为腹膜内膜样腺癌.例2由输卵管型上皮细胞构成,细胞呈腺管状、乳头状结构,诊断为腹膜浆液性腺癌.2例肿瘤细胞均表达间皮素(mesothelin,MSLN)、CA125等卵巢上皮抗原.结论 大网膜腺癌病理学形态、临床经过与卵巢原发上皮癌无差别,分子改变有差异.     

自噬基因Beclin-1与凋亡基因Bax、Bcl-2在子宫腺肌病中的表达及意义

目的探讨子宫腺肌病与子宫内膜样腺癌中细胞自噬基因Beclin-1、凋亡基因Bax、Bcl-2的表达及意义。方法采用免疫组化sP法检测82例子宫腺肌病、40例子宫内膜样腺癌组织中自噬基因Beclin-1、凋亡基因Bax、Bcl-2的表达水平。结果子宫腺肌病中异位子宫内膜及子宫内膜样腺癌中Beclin-1表达水平低于正常子宫内膜组织（P〈0．05）;Bec—lin-1表达随着临床症状严重程度而下调（P〈0．05）。在正常子宫内膜组织中Bax微弱表达,Bcl-2未见表达,两者在子宫腺肌病及子宫内膜腺癌中的表达均显著上调。Bax蛋白表达随腺肌病严重程度增加而增加,Bcl-2的表达则相反（P〈0．05）。结论子宫腺肌病与子宫内膜样腺癌类似,其发生、发展中自噬基因Beclin-1、凋亡基因Bax、Bcl-2起到协调作用。     

子宫内膜不典型息肉状腺肌瘤5例临床病理分析

目的探讨子宫内膜不典型息肉状腺肌瘤(atypical polypoid adenomyomas,APA)的临床与病理学特点。方法分析5例APA的临床资料、病理学形态、免疫组化标记及4例随访资料。结果5例APA中,1例合并子宫内膜样腺癌,1例局部分布分化良好的腺癌成分;免疫组化显示:间质SMA( ),desmin( )或局部( ),vimentin局部( )或(-);腺上皮ER、PR均( );p53、Ki-67(-)。随访的4例患者均健在(3~60个月)。结论APA需与高分化的子宫内膜样腺癌鉴别,后者可与APA并存,或起源于子宫内膜不典型息肉状腺肌瘤,具有低恶性潜能和潜在的复发性,长期随访十分必要。     

青年妇女子宫内膜癌刮宫活检的病理分析

目的 探讨青年妇女子宫内膜癌刮宫活检的病理特点.方法 回顾分析16例40岁以下子宫内膜癌患者临床病理资料.结果 子宫内膜样腺癌14例,腺鳞癌(腺癌伴鳞状上皮分化)1例,浆液性乳头状癌并透明细胞癌1例.子宫内膜样腺癌的组织学特点是子宫内膜腺体失去极性:细胞核变大、变圆、核仁突出,染色质粗或呈空泡状,同时子宫内膜间质消失,代之为肉芽组织或纤维组织,常有炎性反应.多累及浅肌层、无转移.结论 青年妇女子宫内膜癌多为高分化子宫内膜样腺癌.应注意与子宫内膜不典型增生及不典型息内状肌瘤鉴别.     

一级子宫内膜样腺癌累及腺肌病临床病理分析

目的探讨子宫内膜一级子宫内膜样腺癌(endometri-oid adenocarcinoma,EA)累及腺肌病(adenomyosis,AM)的临床病理特点及鉴别诊断。方法观察2例子宫内膜一级EA累及AM的临床病理和免疫组织化学特点,并复习相关文献。结果 2例患者均为中年妇女,年龄分别为47、52岁,表现为进行性痛经伴月经量增多和经期延长,彩色超声示子宫内膜增厚、子宫增大伴肌壁间不均匀回声。病理检查:大体观察子宫增大,子宫壁增厚,子宫体底部子宫内膜局限型结节状和息肉状肿块。镜下为子宫内膜无肌层侵犯的一级EA,肌层内受癌累及AM腺体与子宫内膜EA形态一致,呈膨胀式扩张推挤周围平滑肌,肿瘤周边可见子宫内膜间质细胞;同时肌层内见未被癌累及的腺体和间质细胞。免疫组化:受癌累及的AM腺体周围及肿瘤周边子宫内膜间质细胞CD10(+),desmin(-)。结论一级EA累及AM确诊主要依靠组织学和免疫组化,病理诊断容易误诊为EA肌层侵犯或AM恶变,应引起注意。     

子宫内膜癌组织内分泌分化及其机制的探讨

目的:探讨子宫内膜癌组织的内分泌分化及其机制。方法:采用免疫组织化学及双重免疫组织化学技术, 观察50例子宫内膜样腺癌及20例正常子宫内膜组织的嗜铬素A(CgA)及CgA/细胞角蛋白(CK)表达。结果:(1)子宫内膜样腺癌组的癌组织中CgA阳性率为44.0%, 明显高于正常子宫内膜组(15.0%, P＜0.05)。正常子宫内膜组织仅见极少量的内分泌细胞, 子宫内膜样腺癌组织中内分泌细胞的数量及染色强度均高于正常子宫内膜组。(2)子宫内膜样腺癌组织中可见同时表达CgA与CK的细胞。结论:子宫内膜样腺癌的内分泌分化是肿瘤异质性的表现。子宫内膜样腺癌组织中存在可向上皮细胞或内分泌细胞分化的"多向分化细胞", 提示子宫内膜样腺癌组织的内分泌分化是肿瘤细胞多向分化的结果。     

Oxidative stress in endometrial hyperplasia

OBJECTIVE: Reactive oxygen species seem to be involved in the onset and promotion of carcinogenesis. In 80% of cases of endometrial adenocarcinoma type I, a clear association exists with endometrial hyperplasia, which is considered a key factor in the endometrial oncological spectrum. The presence or absence of atypical cells determines oncological potential. This study explored the behavior of oxidative stress (catalase and malondialdehyde) in endometrial hyperplasia (with or without atypical cells) by comparing it with the oxidative stress existing in both the proliferative and secretory phases. DESIGN: Endometrial specimens from 55 women were used, 32 of which were histologically diagnosed as physiological (17 proliferative and 15 secretory endometria) and 23 as endometrial hyperplasia (18 nonatypical and 5 atypical endometrial hyperplasia). RESULTS: Significant differences were found in the malondialdehyde variable between the proliferative endometrium and the endometrium with atypical hyperplasia (P = 0.0208) and between both types of endometrial hyperplasia (P = 0.0441). The other comparisons were not statistically significant. No changes in catalase activity were observed. CONCLUSION: Our findings seem to suggest that the presence of atypical cells in endometrial hyperplasia induces a reduction in lipid peroxidation, which could permit survival and growth of these cells. This possible decrease in lipid peroxidation does not seem to be mediated by an increase in endometrial catalase activity.     

Interpretation of endometrium obtained by the Endo-pap sampler and a clinical study of its use

Endometrical cytology sampling using the Endo-pap sampler is an inexpensive, painless, and simple procedure. Tissue microfragments obtained include surface epithelial sheets, gland segments, and stromal cell aggregates. Gland segments are critical for evaluation of the sample. Glands are dilated in hyperplasia and there is nuclear crowding with increase of chromatin and nucleoli. In adenocarcinoma there is loss of glands with marked nuclear enlargement and pleomorphism. An understanding of endometrial histomorphology and its correlation with cytology is essential for accurate interpretation. In 1027 ambulatory patients screened, no complications were observed and 92% of the samples were adequate for cytologic diagnosis. Tissue diagnosis was obtained in 173 cases. There were 36 adenocarcinomas, of which 34 (94%) were diagnosed cytologically. There were 16 hyperplasias, of which 5 (31%) were diagnosed cytologically. The Endo-pap sampler was found effective in detecting endometrial adenocarcinoma. Further studies are needed to determine its diagnostic effectiveness in hyperplasia.     

Endometrial brush cytology of advanced postmenopausal endometrium: Does endometrial intraepithelial neoplasia exist in the absence of hyperplasia?

Postmenopausal uterine bleeding is an indication to sample the endometrium for diagnostic purposes. The endometrial brush cytologies of 20 advanced postmenopausal women collected at the time of hysterectomy in order to benchmark the expected morphology of postmenopausal endometrial brushings were reviewed. No women had symptoms or gross findings of primary endomyometrial disease. Endometrium was collected at the surgical pathology laboratory using the Tao Brush and CytoRich Fixative System. After formalin fixation of the uterus, the entire endometrium was embedded for routine histology. Sixteen endometrial brushings and matched endometrial sections showed endometrial atrophy, one brushing showed many ciliated epithelial cells, and three brushings showed focal (less than 10%) epithelial-cell atypia. In two atypias, abnormal endometrial epithelial-cell sheets contained enlarged, clear nuclei with nuclear notches and grooves resembling papillary thyroid cancer. One case showed no histological counterpart to this finding. The other case showed thickening of the pericornual fundic endometrium with cystic glands. The third case with epithelial atypia showed abnormal endometrial-cell sheets with nuclei resembling atypical hyperplasia or type I endometrial adenocarcinoma; corresponding endometrial tissue sections showed rare, irregular glands and back-to-back gland clusters with equivalent nuclear features. Atypical epithelium may be found in atrophic uteri in the absence of gross endometrial thickening. This may be a common event related either to de novo intraepithelial dysplasia in a noncycling endometrium or to hyperplasia that has partly regressed with estradiol withdrawal. This study shows that, in addition to endometrial intraepithelial carcinoma (EIC), isolated atypical glands with morphological and immunohistochemical features of atypical hyperplasia or type I endometrial adenocarcinoma may be found in grossly normal advanced postmenopausal endometrium of asymptomatic patients. This atypical epithelium is readily apparent in endometrial brush preparations, but requires serial sectioning of the endometrium to be demonstrated histologically. We have not established the natural history of this lesion, and in the absence of EIC or gross endometrial thickening indicative of atypical hyperplasia, we do not know whether this degree of epithelial atypia should be an indication for hysterectomy. Diagn. Cytopathol. 1998;19:338–343. © 1998 Wiley-Liss, Inc.     

Laser-captured microdissection-microarray analysis of the genes involved in endometrial carcinogenesis: stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria and its functional relevance

Endometrial carcinoma often arises from normal endometrial glandular cells via a precursor, atypical endometrial hyperplasia. However, the genetic changes involved in this carcinogenetic process are not fully understood. Differentially expressed genes were selected from glandular cells of normal proliferative-phase endometria, atypical endometrial hyperplasia, and endometrial carcinoma using laser-captured microdissection and microarray. The microarray analysis revealed a total of 51 genes to be up-regulated and 23 genes to be down-regulated in neoplastic endometrial epithelia. We focused on lipocalin2 (LCN2), which showed the largest magnitude of up-regulation. Immunostaining for lipocalin2 confirmed a stepwise increase in its expression in endometrial hyperplasia and carcinoma. In addition, elevated expression of lipocalin2 was correlated with the poor outcome of endometrial carcinoma patients. The subcellular distribution of lipocalin2 was both cytoplasmic and nuclear, despite reports that lipocalin2 is a secretory protein. Treatment of endometrial carcinoma cells with 5-azacytidine increased the expression of lipocalin2, suggesting the expression to be controlled by methylation of the promoter. The forced expression of lipocalin2 resulted in the enhanced cell proliferation and invasion in vitro. The expression of lipocalin2 increased with the endometrial carcinogenesis, and accumulation of the protein conferred biological aggressiveness to endometrial carcinoma cells. These results suggest lipocalin2 to be a novel target in the treatment of endometrial carcinoma.     

Endometrial response to raloxifene compared with placebo, cyclical hormone replacement therapy, and unopposed estrogen in postmenopausal women.

OBJECTIVE: To determine the endometrial effects of raloxifene 60 mg/day in postmenopausal women as assessed by vaginal bleeding and endometrial thickness. DESIGN: Data from 1157 postmenopausal women were analyzed from a database consisting of four independent, double-blind, randomized, placebo-controlled trials (range = 6-30 months duration), a 24-month open-label randomized, cyclical hormone replacement therapy (HRT)-controlled trial, and a 6-month double-blind, randomized, unopposed estrogen-controlled trial. Vaginal bleeding rate was derived from self-reported adverse events collected at least every 6 months. Endometrial thickness was measured by ultrasonography at regular intervals. RESULTS: Raloxifene 60 mg/day was not significantly different from placebo with regard to the incidence of vaginal bleeding, the baseline-to-endpoint change in endometrial thickness, or the proportion of women experiencing an increase in endometrial thickness above baseline after either 12 or 24 months of therapy. Unexpected bleeding was reported significantly more frequently in the unopposed estrogen groups compared with the raloxifene group (raloxifene 60 mg/day, 0% versus estrogen, 50%; p = 0.002). A significantly greater baseline-to-endpoint increase in endometrial thickness was observed in both the HRT and estrogen groups compared with their respective raloxifene comparison group (raloxifene 60 mg/day, 0.01 +/- 2.0 mm versus HRT, 1.8 +/- 3.2; p < 0.001; raloxifene 60 mg/day, 1.1 +/- 1.7 mm versus estrogen, 7.8 +/- 3.8; p < 0.001). No cases of endometrial hyperplasia or cancer were diagnosed in the placebo or raloxifene 60 mg/day groups. Endometrial hyperplasia was diagnosed in one case in the HRT group and in two cases in the estrogen group. CONCLUSION: Raloxifene 60 mg/day for up to 30 months is not associated with vaginal bleeding or increased endometrial thickness in postmenopausal women.     

Cell cycle analysis and detection of proliferative cell nuclear antigen of the endometrium after hormone replacement therapy

Background: To understand the effect of sequential combined hormone replacement therapy (HRT) on the postmenopausal endometrium. Methods: Sonographic endometrial thickness, endometrial histopathology, flow cytometric cell cycle analysis and the level of proliferative cell nuclear antigen (PCNA) were studied. Results: One hundred and thirty-eight postmenopausal women were enrolled in this study. Among which, 97 women had their endometrium being adequately obtained; the most frequent type of histopathology was normal endometrium (91.8%). Endometrial hyperplasia was found in seven patients (7.2%), including typical simple hyperplasia (n=1, 1%), focal simple hyperplasia (n=5, 5.2%) and complex hyperplasia without atypia (n=1, 1%). The proliferative fractions (PF; S plus G₂–M phase) of cells from normal and hyperplastic endometrium of menopausal women after HRT were 8.18 and 8.95%, respectively, which were lower than those from 29 premenopausal women without HRT. The level of PCNA of normal and hyperplastic endometrium in postmenopausal women after HRT was about 80 and 84%, respectively, of that from premenopausal endometrium. Conclusions: Our study showed the PF of the cell cycle and the level of PCNA were not increased in the menopausal endometrium under HRT as compared to the premenopausal controls.     

Thymidine phosphorylase expression in normal and hyperplastic endometrium

AIMS: To investigate the expression of thymidine phosphorylase (TP), a known angiogenic factor for endothelial cells, in normally cycling endometrium and various forms of endometrial hyperplasia. METHODS: TP expression was assessed with the P-GF.44C monoclonal antibody, using the alkaline phosphatase anti-alkaline phosphatase method. Ninety two normal and hyperplastic endometria were studied. RESULTS: In normal proliferative endometrium, TP is found exclusively in the basal layer and the inner third of the functionalis; expression is cytoplasmic in glandular epithelium and nuclear in stromal cells. It is invariably patchy. This immunohistochemical picture remains almost unaltered during the early and mid secretory phase of the normal menstrual cycle but, most impressively, TP is expressed uniformly in the epithelium of all endometrial glands towards the end of the cycle. At this stage, expression is mixed nuclear/cytoplasmic and there is very little stromal nuclear staining. In simple endometrial hyperplasia, the staining pattern for TP is identical to normal proliferative endometrium, with a distribution that is usually limited to a few rather weakly proliferating glands and to the adjacent periglandular stroma of the deep endometrium. The distribution is more extensive in complex and atypical endometrial hyperplasias, where a mixed nuclear/cytoplasmic pattern usually prevails over the pure cytoplasmic reaction. CONCLUSIONS: TP is expressed consistently in normal and hyperplastic endometrium, suggesting a role in physiological and pathological angiogenesis. In normal endometrium, TP has a definite pattern of distribution, which is dependent on the phase of the menstrual cycle, whereas in all forms of endometrial hyperplasia the enzyme is randomly distributed and lacks an orderly pattern.     

Immunohistochemical estrogen receptor assessment in hyperplastic, neoplastic, and physiologic endometria

Endometrial hyperplasias and some endometrial carcinomas arise in a setting of estrogen excess. Steroid hormones interact with cells via specific receptors; assessing receptor levels may indicate a tissue's potential for interaction with that hormone. To examine estrogen receptor (ER) levels in endometrial hyperplasia, endometrial carcinoma, and physiologically cycling endometrium, an immunohistochemical technique utilizing a monoclonal anti-estrophilin (estrogen receptor) antibody was applied to formalin-fixed, paraffin-embedded tissue. In complex hyperplasia and grade I adenocarcinoma, the mean percentages of epithelial cells demonstrating nuclear staining for ER was mildly decreased compared to proliferative endometrium. A trend was noted toward less ER staining in atypical hyperplasia compared to non-atypical complex hyperplasia. ER varied with physiologic cycling of the endometrium. ER was also present in atrophic endometrium, myometrium, adenomyosis, and leiomyomata. Immunohistochemistry permits localization of ER and is a useful technique in ER assessment of endometrial hyperplasias and carcinomas.     

Cytologic criteria of hyperplastic lesions in endometrial samples obtained by the endocyte sampler

The present investigation attempted to identify useful parameters for the cytologic diagnosis of endometrial hyperplasias in samples obtained with the Endopap endometrial sampler. A clinical and morphological classification dividing hyperplasia into benign simple hyperplasia (BSH); benign complex hyperplasia (BCH); and endometrial intraepithelial neoplasia (EIN) has been suggested by Meisels, et al. based on five valuable cytologic criteria. To these we added six of our own and applied them to 1.172 cases, 432 of which had a previous histologic diagnosis of normal proliferative endometrium (NPE); 462 were BSH, 210 were BCH, and 14 fit the EIN pattern. The cytologic criteria evaluated were overlapping cells, enlarged nuclei, aniso karyosis, granularity of chromatin, stromal cells, branching glandular structures, and moruloid or papillary-like cellular aggregates, dilated glandular borders in cellular sheets, nuclear clearing, clumped chromatin, and enlarged eosinophilic cytoplasm. Our results are consistent with the following findings: (1) there is no useful parameter for cytologic differentiation between NPE and BSH; (2) BCH is characterized by cellular aggregates, dilated glandular borders in cellular sheets, and branching glandular structures; (3) EIN is characterized by nuclear clearing, clumped chromatin, and anisokaryosis; and (4) enlargement of nucleoli and eosinophilic cytoplasm alone is not sufficient for the diagnosis of EIN.     

Genetic imbalances in precursor lesions of endometrial cancer detected by comparative genomic hybridization

Endometrial hyperplasia is regarded as a precursor lesion of endometrioid adenocarcinomas of the endometrium. The genetic events involved in the multistep process from normal endometrial glandular tissue to invasive endometrial carcinomas are primarily unknown. We chose endometrial hyperplasia as a model for identifying chromosomal aberrations occurring during carcinogenesis. Comparative genomic hybridization (CGH) was performed on 47 formalin-fixed, paraffin-embedded specimens of endometrial hyperplasia using the microdissection technique to increase the number of tumor cells in the samples and reduce contamination from normal cells. CGH analysis revealed that 24 out of 47 (51%) samples had detectable chromosomal imbalances, whereas 23 (49%) were in a genetically balanced state. The incidence of aberrant CGH profiles tended to parallel dysplasia grade, ranging from 22% aberrant profiles in simple hyperplasia to 67% in complex hyperplasia with atypia. The most frequent imbalances were 1p, 16p, and 20q underrepresentations and 4q overrepresentations. Copy number changes in 1p were more frequent in atypical complex hyperplasia than in complex lesions without atypical cells or simple lesions (42% versus 20% and 0%). Our results show that endometrial hyperplasia reveals recurrent chromosomal imbalances which tend to increase with the presence of atypical cells. The most frequent aberrations in endometrial cancer, 1q and 8q overrepresentations, are not present or are rare in its precursor lesions. This analysis provides evidence that tumorigenesis proceeds through the accumulation of a series of genetic alterations and suggests a stepwise mode of tumorigenesis.