Endometrioid carcinoma of the endometrium: pathologic and molecular features

Endometrioid carcinoma of the endometrium is the most common type of endometrial carcinoma. The microscopic appearance of the tumor resembles that of the proliferative endometrium, with a variable degree of glandular complexity and cellular pleomorphism. Several subtypes have been described, including the presence of squamous differentiation, villoglandular pattern, secretory features and ciliated cells. Recently recognized subtypes are the tumors that arise in the setting of hereditary nonpolyposis colon cancer syndrome, tumors with small nonvillous papillae, presence of microglandular pattern, sertoliform features, and dedifferentiated carcinomas. The main differential diagnosis includes endocervical adenocarcinoma, atypical polypoid adenomyoma, malignant mixed Müllerian tumors, and metastatic tumors to the endometrium. The main prognostic factors are stage, histologic grade, myometrial, cervical and vascular invasion. There are several pathologic features that should be recognized to avoid underestimation of these prognostic factors, such as presence of MELF pattern of myometrial invasion, and invasion of the cervical stroma with a deceptive pattern of spread. Six different molecular features are frequent in this type of tumor, including microsatellite instability, and mutations in PTEN, k-RAS, PIK3CA, FGFR2 and CTNNB1.     

雌激素与子宫内膜癌

子宫内膜癌是妇科常见的恶性肿瘤。既往报道其发生率约为女性生殖器官恶性肿瘤的第三位。因子宫内膜癌发病年龄较宫颈癌后延十年左右，随着全球妇女人均寿命的延长，雌激素替代疗法的日益增多等因素，故发生率呈上升趋势，九十年代在美国等发达国家的发病率已为女性生殖器...     

子宫内膜癌的临床病理研究

子宫内膜癌是妇科常见的恶性肿瘤,近年来其发病率逐年增高并与子宫颈癌发病率逐渐接近,已受到国内外学者的关注。一般认为,其临床预后与临床分期病理分级、肌层浸润程度等因素有关。本文仅就临床病理与预后有关的几个问题进行探讨。     

Expression of secretagogin in clear-cell renal cell carcinomas is associated with a high metastasis rate

Renal cell carcinomas are divided into several subgroups according to their histopathologic characteristics. The outcome, therapy responses, and the applicability of molecular-targeted therapies depend on the tumor classification and on the tumor stage. Recent advances within the biomarker research facilitated the exact classification of the molecular character of the renal tumor. For example, the calcium-binding proteins parvalbumin and S-100A1 are characteristically expressed in renal cell carcinoma subgroups. This led us to investigate the expression of the novel calcium-binding protein secretagogin in renal cell carcinomas. Tissue microarray cylinders including 94 clear-cell renal cell carcinomas, 61 non-clear-cell renal cell carcinomas (37 papillary renal cell and 24 chromophobe carcinomas), and 30 oncocytomas were analyzed by immunohistochemistry. This showed remarkable secretagogin expression in 37% of the clear-cell renal cell carcinomas. Non-clear-cell renal cell carcinomas and oncocytomas were completely negative. Consequently performed immunoblotting analyses confirmed this expression profile. Because publicly available data direct toward a formation of a hierarchical cluster of secretagogin overexpressing clear-cell renal cell carcinomas, we conducted a clinical follow-up of the patients with clear-cell renal cell carcinoma. This revealed significantly more metastasis within the secretagogin-positive clear-cell renal cell carcinoma subgroup (49% versus 28%; P < .05). In conclusion, we report on detection of the novel calcium-binding protein secretagogin within a subgroup of clear-cell renal cell carcinomas. The increased metastasis rates within the secretagogin-positive subgroup of clear-cell renal cell carcinomas direct toward a clinical impact of our findings.     

When to suspect and how to diagnose syndromic polyps and carcinomas of the gastrointestinal tract: focus on Lynch syndrome and colonic hamartomatous polyposis

An estimated 130,000 individuals are diagnosed with colorectal carcinoma each year, and approximately 50,000 will die from this disease, making colorectal carcinoma the third leading cause of cancer deaths in the United States.¹ Heritable forms of colorectal carcinoma are common. These heritable conditions may manifest as a polyposis or as colorectal carcinoma. In this review, the pathology of hamartomatous polyps will be discussed with particular emphasis on clues that should alert pathologists to the possibility of a polyposis syndrome. This review will also provide tools for pathologists to identify patients at risk for Lynch syndrome.     

Galectin-3 expression in normal,hyperplastic, and neoplastic endometrial tissues

This study evaluated the expression of galectin-3 in 101 curettage specimens from normal, hyperplastic, and neoplastic endometrial tissues using immunohistochemistry. The histologic diagnoses were as follows: normal proliferative (n = 8) and secretory (n = 4) phase, simple hyperplasia (SH, n = 16), complex hyperplasia without atypia (CH, n = 11), atypical hyperplasia (AH, n = 13), endometrioid adenocarcinoma (EC, n = 35), serous papillary carcinoma (SPC, n = 10), and clear cell carcinoma (CC, n = 4). Immunostaining was scored with regard to the approximate percentage of positive tumor cells and relative staining intensity. The scores of immunostaining increased significantly from NE, SH, CH, and AH to the adenocarcinomas (ANOVA, p < 0.0001). Subsequently, three significantly different levels of galectin-3 expression were found (Newman-Keuls multiple comparison test). These consisted of (a) NE, SH, and CH, (b) AH and EC, and (c) SPC and CC. Galectin-3 expression increased with tumor grade (ANOVA, p = 0.0026). The scores of FIGO stages I to III did not differ significantly (ANOVA, p = 0.1687). Enhanced nuclear galectin-3 expression was noted in carcinomas, immunostaining of stromal cells decreased in the latter. This study shows that galectin-3 expression increases from normal and hyperplastic to atypical hyperplastic and cancerous states of endometrial tissues, and provides further evidence of a relationship between AH and EC.     

Prediction of coexistent carcinomas risks by subjective EIN diagnosis and comparison with WHO classification in endometrial hyperplasias

Endometrial intraepithelial neoplasia (EIN) classification is proposed as a new diagnostic system to resolve the limitations of the World Health Organization (WHO) classification in routine practice. Our aim was to find out whether EIN classification excels the WHO classification regarding the accurate prediction of coexisting endometrial carcinomas (EC) in biopsy specimens.     

Glycogen-rich pleomorphic xanthoastrocytoma with clear-cell features: confirmatory report of a rare variant with implications for differential diagnosis

Central nervous system space-occupying lesions with clear-cell features encompass a nosologically heterogeneous array, ranging from reactive histiocytic proliferations to neuroepithelial or meningothelial neoplasms of various grades and to metastases. In the face of such differential diagnostic breadth, recognizing cytoplasmic lucency as part of the morphological spectrum of some low grade gliomas will directly have an impact on patient care. We describe a prevailing clear-cell change in an epileptogenic left temporal pleomorphic xanthoastrocytoma surgically resected from a 36-year-old man. Mostly subarachnoid and focally calcified, the tumor was composed of fascicles of moderately atypical spindle cells with optically lucent cytoplasm that tended to intermingle with a desmoplastic mesh of reticulin fibers. Immunohistochemically, coexpression of S100 protein, vimentin, GFAP, and CD34 was noted. Conversely, neither punctate staining for EMA nor positivity for CD68 was seen. Mitotic activity was absent, and the MIB1 labeling index was 2-3% on average. Diastase-sensitive PAS-positive granula indicated clear-cell change to proceed from glycogen storage. Electron microscopy showed tumor cell cytoplasm to be largely obliterated by non-lysosomal-bound pools of glycogen, while hardly any fat vacuole was encountered. Neither ependymal-derived organelles nor annular lamellae suggesting oligodendroglial differentiation were detected. The latter differential diagnosis was further invalidated by lack of codeletion of chromosomal regions 1p36 and 19q13 on molecular genetic testing. By significantly interfering with pattern recognition as an implicit approach in histopathology, clear-cell change in pleomorphic xanthoastrocytoma is likely to suspend its status as a “classic”, and to prompt more deductive differential diagnostic strategies to exclude look-alikes, especially clear-cell ependymoma and oligodendroglioma.     

年轻妇女早期子宫内膜癌的治疗进展

目的：探讨有关年轻妇女早期子宫内膜癌的治疗进展现状。方法：广泛查阅国内外有关年轻妇女早期子宫内膜癌治疗进展的资料,并进行分析和总结。结果：年轻患者多有不孕不育史,强烈要求保留生育或生理功能,而早期子宫内膜癌多为高分化,进展缓慢,无肌层浸润或肌层浸润浅,预后较好,这使保留生育或生理功能的治疗成为可能。结论：近年来子宫内膜癌在世界范围内发病率均有上升趋势,且年轻患者发病率逐渐增高。年轻妇女早期子宫内膜癌患者是否保留生育或生理功能等治疗仍然存有争议,对这一问题还需深入研究和探讨。     

Expression and Clinical Significance of Ghrelin in Endometrial Hyperplasia and Carcinoma of Egyptian Patients

Endometrial carcinoma ranks the seventh most common malignant tumor worldwide. The distinction between atypical endometrial hyperplasia (AEH) and endometrial carcinoma, especially the well-differentiated grade, is particularly difficult with overlapping distinguishing criteria and small biopsy. Ghrelin is 28 amino acid peptide that is synthesized by gastric mucosa and is expressed in a variety of normal and tumor tissues. In endometrial tissue, it is expressed during the menstrual cycle, involved in the uterine development and cyclic growth. Data regarding role of Ghrelin in endometrial carcinoma are contradictory. In the present study, immunohistochemical expression of Ghrelin was evaluated in 55 endometrioid carcinoma cases, as well as 26 endometrial hyperplasia cases. The relationship between Ghrelin expression and clinicopathologic features of endometrioid carcinoma was studied as well. Ghrelin loss or reduced expression was significantly related to endometrioid carcinoma, especially the well-differentiated type, compared with AEH and EIN (p?=?0.000 and 0.006, respectively). Ghrelin loss was also related to poorly differentiated histologic grades of endometrioid carcinoma (p?=?0.04). Ghrelin loss is helpful in differentiation between AEH and EIN from endometrioid adenocarcinoma, especially the well-differentiated grade. It could be also related to poor differentiation.     

PTEN及p27Kip1在子宫内膜癌中的研究进展

肿瘤抑制基因PTEN被称为子宫内膜的看家基因,许多学者提出PTEN基因在子宫内膜癌发生发展中起重要作用。另一个肿瘤抑制基因p27在子宫内膜癌的预后中具有重要的作用。现就PTEN 、p27基因在子宫内膜癌中的表达及其与子宫内膜癌发生、发展的关系以及在治疗和预后方面的研究进展进行综述。     

Morphologic Correlates of Host Response in Endometrial Carcinoma*

ABSTRACT: Cases of endometrial carcinoma reviewed for this study were divided into two groups: 1) Premenopausal, perimenopausal and postmenopausal patients in whom a history of anovulation, obesity, ovarian hyperthecosis (including Stein-Leventhal syndrome) or feminizing tumors, and/or exogenous estrogen intake were found; and 2) postmenopausal, elderly patients, without known hormonal or metabolic disturbances and without any history of estrogen therapy. In the first group, frequent associated findings were precursor stages of endometrial carcinoma, such as adenomatous and atypical hyperplasia. In the majority of cases, the cancer was confined to the endometrium, rarely infiltrating the myometrium. In the second group, the cancer was associated most often with an inactive, atrophic endometrium and frequently diffusely infiltrated through the myometrium, with lymphatic and vascular involvement. The lymphatic and plasma-cell infiltrate was evaluated in both groups. It was found to be more abundant in the first group, both at the tumor-host interface and perivascularly, than in the second. As reported in other malignancies of the female reproductive system, the presence or absence of a lymphocytic infiltrate as a morphological expression of local cellular immune response of the host correlates well with the biological behavior of the tumor. A challenging question is the relationship, if any, between hormonal factors and immune mechanisms in tumors arising in tissues such as the endometrium that, even normally, are targets of hormonal stimulation.     

Comparison of benign and malignant endometrial lesions for their p53 state, using immunohistochemistry and temperature-gradient gel electrophoresis

The aim of this study was to evaluate the presence and distribution of p53 alterations in pure endometrioid adenocarcinomas (n=120) of different grades and stages, as opposed to normal endometrium (n=13) and various risk groups of hyperplasia (n=39). All samples were initially analysed by immunohistochemistry with the monoclonal antibody Ab-6. Normal endometria were negative. With increasing degrees of malignancy, the number of cases with p53 accumulation rose and ranged from 9% to 18% in hyperplasia, through 25% in lowgrade carcinomas (G1), to 69% in high-grade carcinomas (G3). This increase was also seen when comparing tumours by stage. Of carcinomas in stage IA, only 17% showed p53 immunostaining, in contrast with 72% in stage IC. Of this material, 34 carcinomas and 8 hyperplasias were analysed for p53 mutations in exons 5–8 by means of polymerase chain reaction and temperature-gradient gel electrophoresis (TGGE). In none of 5 hyperplasia and 6 of 12 carcinomas showing p53 accumulation by immunohistochemistry, p53 mutations were detected by TGGE. In contrast, 4 of 22 carcinomas harboured mutant p53 but were negative by immunohistochemistry. Immunohistochemical and molecular investigations revealed that p53 alterations are related to the standard prognostic markers of endometrial cancer, i.e. grading and staging. TGGE, an indirect screening procedure for p53 mutations, is used to detect the type of p53 alteration and may provide additional insight into the complex figure of p53 abnormalities in the development and progression of malignant endometrial lesions.     

MIB-1 Expression in breast carcinomas with medullary features

Bcl-2 and Bax proteins, which are involved in repressing and promoting programmed cell death, respectively, have been investigated immunohistochemically and by Western blot analysis in a series of thyroid tumours. Three immunostaining patterns were identified. Benign lesions and well-differentiated thyroid carcinomas displayed a profile similar to that of normal follicular epithelium, in which Bcl-2 immunostaining was predominant. Thyroid carcinomas associated with an aggressive behaviour, such as the tall-cell variant of papillary carcinoma and the poorly differentiated carcinomas, co-expressed both proteins. Finally, anaplastic carcinomas expressed only the Bax protein. Western blot analyses revealed that the anti-Bcl-2 antibody recognized two bands, of molecular weights 21 kDa and 25 kDa. This was only seen in the tall-cell papillary carcinomas and in the anaplastic carcinomas.     

子宫内膜癌组织中cyclin E和p27表达的相关性及其与临床预后的关系

目的 :探讨子宫内膜癌组织中cyclinE与 p2 7表达的相关性及其与临床预后的关系。方法 :用免疫组化方法检测 40例子宫内膜癌、10例子宫内膜不典型增生、2 0例正常子宫内膜组织中cyclinE和p2 7的表达 ,并用Log Rank检验p2 7蛋白和cyclinE蛋白表达与子宫内膜癌患者生存率的关系。结果 :cyclinE表达的阳性率 ,子宫内膜癌组显著高于内膜不典型增生组和正常子宫内膜组 (P <0 .0 5 )。p2 7表达与子宫内膜癌的组织学分级、手术分期及肌层浸润深度有关 (P <0 .0 5 )。cyclinE与p2 7的表达呈负相关。cyclinE蛋白表达阳性患者生存率低于阴性患者 ,p2 7蛋白表达阳性患者生存率高于阴性患者 ,但无统计学意义 (P >0 .0 5 )。结论 :cyclinE对子宫内膜癌的发生可能起一定作用 ,p2 7则与抑制子宫内膜癌的进展有关 ,并可能成为判断预后的有用指标