Endometrial Carcinoma Group Research Articles

Parameters linked with malignancy in postmenopausal endometrial polyps

Purpose: To utilize the aid of transvaginal (TV) elastosonography (ES) in the differentiation of endometrial hyperplasia and endometrium carcinoma (ca) and to compare these yields with the results of normal endometrium SE of post-menopausal patients. Material and methods: 136 patients with the complaints of postmenopausal hemorrhage and/or of the normal control TVUltrasonography (US) between February and October 2013 were included in this research. TV-elastosonography (ES)was performed under the samemonitor consecutivelywith the TV-US. Strain index (SI) was recorded for each patient, Kolmogorov–Smirnov test for Normal variables, Student’s t test, Kruskal Wallis Analysis of Variance test, Mann Whitney U Test with Bonferroni Correction was applied for pairwise statistics. Receiver Operating Characteristics (ROC) curvewasfitted inorder to characterize thegroupdifferences in terms of sensitivity and specificity scores. Results: The SI values of normal control group, endometrial carcinoma and hyperplasia groups were compared to each other statistically, no significant statistical differences between hyperplasia and control groups, but a significant statistical differencewas introduced for the endometrial carcinoma against these hyperplasia and control groups (p=0.000). In real-time ES; the scoring of elasticity patterns between endometrial ca and hyperplasia presented 81.3% sensitivity, 100% specificity and PPV, 70% NPV. Conclusion: Real time-elastosonography is a complementary semi-quantitative method compared to the other cross-sectional imaging methods, provides valuable information especially for the endometrial pathologies.

Association of the apolipoprotein E 2 allele with concurrent occurrence of endometrial hyperplasia and endometrial carcinoma.

Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n = 89), EH concurrent with ECa (n = 76), ECa (n = 186), and healthy controls (n = 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys), iron (HFE Cys282Tyr and His63Asp), and catecholamines (COMT Val158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys) was higher in patients with EH + ECa than in controls (P = 0.0012, P Bonferroni = 0.018, OR = 2.58, 95% CI 1.49–4.45). The APOE E 4 allele (112Arg) was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp) had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa.

Variants in DENND1A and LHCGR are associated with endometrioid adenocarcinoma

ObjectiveThe aim of this study was to explore the polycystic ovary syndrome (PCOS) related single nucleotide polymorphisms (SNPs) rs13405728 (in gene LHCGR), rs13429458 (in gene THADA) and rs2479106 (in gene DENND1A) in women with endometrial carcinoma. MethodsWe conducted a case–control study comprising 96 Han Chinese women with endometrial carcinoma, and 192 healthy controls. SNPs rs13405728, rs13429458 and rs2479106 were genotyped by polymerase chain reaction (PCR) and direct sequencing. The effects of body mass index (BMI) and age were evaluated using an unconditional logistic regression model adjusted for potential confounders. ResultsThe allele frequencies of SNPs rs2479106 and rs13405728 were significantly different (P<0.05) between endometrial carcinoma group and control group, and the difference was especially significant in the subgroup of endometrioid adenocarcinoma. Genotyping analysis showed that allele G in rs2479106 and allele A in rs13405728 could confer risk to endometrioid adenocarcinoma. ConclusionsOur results suggest that SNPs rs2479106 in gene DENND1A and rs13405728 in gene LHCGR are associated with endometrioid adenocarcinoma.

Clinical value of combined detection of serum human epididymal secretory protein E4 and CA(125) in the diagnosis of endometrial carcinoma

To explore the clinical value of combined detection of serum human epididymal secretory protein E4 (HE4) and CA(125) in the diagnosis of endometrial carcinoma. From Jan 2010 to Apr 2011, the serum specimens were collected from 124 cases of endometrial carcinoma, 97 cases of benign disease of uterus and 109 cases of healthy women. HE4 levels in the serum were detected by ELISA, and CA(125) levels in the serum were detected by the electro-chemiluminescent immunoassay. Those results were shown with median level. Accuracy of the diagnosis was evaluated by the area under the receiver operating characteristic curve (ROC-AUC). The median levels of HE4 and CA(125) were 78.09 pmol/L and 33.43 kU/L in serum of endometrial carcinoma group. The median levels of HE4 and CA(125) were 46.37 pmol/L and 18.26 kU/L in serum of benign disease of uterus group. The median levels of HE4 and CA(125) were 31.75 pmol/L and 12.64 kU/L in serum of healthy women group. The HE4 and CA(125) levels in serum of endometrial carcinoma group were significantly higher than those of benign disease of uterus group or healthy women group (all P < 0.05). Compared with that benign disease of uterus group, the ROC-AUC of HE4 and CA(125) in endometrial carcinoma group were 0.913 and 0.801, respectively. When the specificity was 95.0%, the sensitivities of HE4, CA(125), and combined detection of HE4 and CA(125) in endometrial carcinoma group were 41.1%, 22.6% and 46.0%, respectively. The positive rates of HE4 and CA(125) were 31% (27/86) and 12% (10/86) in stage I-II of endometrial carcinoma, while the positive rates were 63% (24/38) and 47% (18/38) in stage III-IV of endometrial carcinoma, in which there were significant difference between patients in stage III-IV and stage I-II (P < 0.01). The combined detection of serum HE4 and CA(125) is helpful to the diagnosis of endometrial carcinoma. The sensitivity, specificity and early diagnosis of HE4 are better than that of CA(125). The positive rates of HE4 and CA(125) in endometrial carcinoma are related to the clinical staging.

An Update on the Management of Uterine Carcinosarcoma

Carcinosarcomas are rare aggressive neoplasms with a poor prognosis. The recent International Federation of Gynecology and Obstetrics (FIGO) 2009 categorizes uterine carcinosarcoma into the endometrial carcinoma group. This review highlights the prognosis, recurrence rate, and the treatment modalities. The primary treatment is surgery. Lymphadenectomy as part of the surgical procedure has shown to prolong survival even for early-stage disease. A combined chemo-radiotherapeutic approach has shown a survival benefit. Radiotherapy from various studies has shown a significant effect on local control of the disease, with no obvious benefit on overall survival. Various trials led by the gynecologic oncology group looking into different chemotherapeutic combinations have showed differing response rates. In the future, the emergence of combination of chemotherapeutic agents with molecular-targeted agents may show promising results. Obstetricians & Gynecologists and Family Physicians. After completing this CME activity, physicians should be better able to appraise the aggressive nature of uterine carcinosarcoma and factors which would help in delaying or preventing recurrence, assess the importance of lymphadenectomy for uterine carcinosarcoma and its effect on survival, and evaluate various recent trials addressing the chemo-radiotherapeutic combinations as adjuvant therapy.

Abstract 900: Tissue CA125 expression levels as a biomarker of endometrial cancer

Abstract Serum CA125 has been recognized as a biomarker of gynecological tumors. However, serum CA125 detection is not very sensitive and specific in the diagnosis of cervical and endometrial carcinoma. This study has investigated the endometrial CA125 expression in patients with endometrial polyps, hyperplasia and carcinoma in comparison with normal endometrium. A total of 242 subjects were recruited into this study and they were classified into six groups, namely proliferative phase endometrium (n = 24), secretory phase endometrium (n = 21), non-functional endometrial polyps (n = 24), simple hyperplasia (n = 24), complex hyperplasia (n = 26), and endometrial carcinoma (n = 126). An immunohistochemistry method was used to detect endometrial CA125 expression. The results showed that there were significant differences in CA125 levels between normal and diseased endometrium, with significantly increased CA125 expression in patients with endometrial polyps, complex hyperplasia, and carcinoma compared to those with normal endometrium. There was only a weak CA125 expression in normal endometrium and simple endometrium hyperplasia. There were significant differences in CA125 expression levels between patients with non-functional endometrial polyps, simple hyperplasia, and complex hyperplasia (χ2 = 9.652, p &amp;lt; 0.005). In endometrial carcinoma group, there was a significant difference in CA125 expression among patients with pathological grade I, II and III of endometrial carcinoma (χ2=11.975, p &amp;lt; 0.01), while there was no significant difference in CA125 expression between grade I and grade II carcinoma (χ2=3.698, p &amp;gt; 0.05). These findings indicate that endometrial CA125 expression can be used as a reliable biomarker in the diagnosis and clinical staging of endometrial carcinoma in Chinese women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 900. doi:10.1158/1538-7445.AM2011-900

Investigation of galectin-3 and heparanase in endometrioid and serous carcinomas of the endometrium and correlation with known predictors of survival

Inhibitors of tumor angiogenesis and metastasis are emerging as important new drug candidates for cancer therapy. Galectin-3 and heparanase have been shown to function in tumor progression and metastatic spread. Both of them exert pleiotropic effects; proliferation, cell migration, differentiation and tissue remodeling. The aim of this study was to investigate heparanase and galectin-3 expression in endometrioid and serous carcinomas of the endometrium and their relation with well-known prognostic factors, in addition to estrogen, progesterone, C-erbB-2, Ki-67 and p53. Sixty-four endometrial cancers, which include 24 serous types, were obtained from previously untreated patients. Immunohistochemical analysis of 64 carcinomas, 20 endometrial hyperplasia (ten of simple hyperplasia and ten of complex atypic hyperplasia) and 20 normal endometrium (ten of proliferative and ten of secretory) was performed. This investigation suggests that the decreased expression of galectin-3 may be involved in the pathogenesis of endometrial carcinomas from normal endometrium to carcinoma. Also down-regulated stromal expression of galectin-3 in endometrial carcinoma may be involved in lymph node metastasis. Further studies on a larger advanced stage (FIGO stage 3-4) endometrial carcinoma group may determine the value of heparanase in the endometrial carcinoma.

Extracellular signal-regulated protein kinase activation in endometrium with polycystic ovary syndrome and its significance

to investigate the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) signaling pathway in the endometrium of women with polycystic ovary syndrome (PCOS) and its effect and significance in the cause of hyperplasia and carcinoma; and investigate the factors which affect the activation of the MAPK/ERK signaling pathway. collected 52 patients diagnosed as PCOS who were taken dilation and curettage of uterus as study, while 32 non-PCOS patients matched as control group. Serum hormonal parameters, fasting blood glucose and insulin were measured in all patients. The PCOS patients were sub-group as insulin resistance group and non-insulin resistance group; all the patients were carried out pathology inspection of endometria, and the PCOS patients were sub-group as endometrial hyperplasia and carcinoma group and normal endometrium group based on the outcome of pathology inspection. Western blot were performed to detect the expressions of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2), the activation of ERK1/2. (1) the expression of p-ERK1/2 [(61 ± 13)%] in the endometrium in PCOS group was higher than that in the control [(44 ± 10)%, P < 0.01]. (2) The expression of p-ERK1/2 was significantly increased in group of endometrial hyperplasia and carcinoma [(70 ± 11)%] compared to that in group of normal endometrium [(55 ± 10)%, P < 0.01], while there were significant difference between group of insulin resistance [(63 ± 13)%] and group of non-insulin resistance [(55 ± 7)%, P < 0.01]. (3)Fasting insulin level, insulin area under the curve and body mass index were related to the expression of p-ERK1/2 in endometrium with PCOS, the correlation coefficient were 0.447, 0.456 and 0.381, respectively (all P < 0.01). the MAPK/ERK signaling pathway in endometrium with PCOS was overactivation, which was related to the endometrial hyperplasia and carcinoma; while the activation of MAPK/ERK signaling pathway were effected by insulin resistance and hyperinsulinemia.

Clinical significance of the expression of serum level of CA125 and survivin protein in endometrial carcinoma

Objective To study clinical significance of the expression of serum level of CA125 and survivin protein in endometrial carcinoma. Methods The normal endometrium group(40 cases) ,atypical endometrial hyperplasia group (40 cases)and endometrial cancer group (40 cases). Compared the changes of serum level of CA125 and the expression of survivin protein between before and after surgery in each group and in different clinical and pathological stagings in the group of endometrial carcinoma. Results The serum level of CA125in endometrial cancer group before and after surgery are significantly higher than other two groups, the differences are statistically significant(P ＜ 0.05 ). Compare survivin positive expression rate and strong positive expression rate in atypical endometrial hyperplasia group and endometrial cancer group with the normal endometrium group, the differences are statistically significant( P ＜ 0.05 ). The rate of positive expression of serum level of CA125 in Ⅱ-Ⅳ period cases of endometrial carcinoma, higher pathological grade cases, deep myometrial invasion cases and recurrence cases is significantly higher. The strongly positive expression of survivin protein in Ⅱ-Ⅳ period cases, G3 cases, deep myometrial invasion cases and recurrent cases is significantly higher. Conclusion It is the significance of guidance for the serum level of CA125 to the surgical pathological staging of endometrial carcinoma. It is the certain reference value for survivin protein to the early diagnosis and clinical prognosis of endometrial carcinoma. Key words: CA125; Survivin protein; Endometrial cancer

Fertility-preserving treatment in young women with well-differentiated endometrial carcinoma and severe atypical hyperplasia of endometrium

A retrospective study on 25 women (8 with endometrial carcinoma, 17 with severe endometrial atypical hyperplasia) under 35 years treated with progestin showed that six cases (75%) in the endometrial carcinoma (EC) group and 17 (100%) in the atypical hyperplasia (AH) group responded to the treatment, and among the 14 complete responders, 4 (40%) patients with AH had 7 pregnancies and 3 healthy deliveries. Given accurate pretreatment assessment, progestin therapy is a feasible management option to preserve fertility for young women with well-differentiated endometrial carcinoma or severe atypical hyperplasia of endometrium.

Concurrent Endometrial Carcinoma in Patients with a Curettage Diagnosis of Endometrial Hyperplasia

Endometrial hyperplasia is considered a precursor of endometrial carcinoma, but concurrent endometrial carcinoma in patients with endometrial hyperplasia is seen frequently. Our aim was to examine the risk factors for coexisting endometrial carcinoma in patients with endometrial hyperplasia. Between January 1996 and September 2006, 77 patients who underwent hysterectomy for endometrial hyperplasia were enrolled retrospectively. We divided the patients into non-endometrial carcinoma and endometrial carcinoma groups, depending on the final pathology of hysterectomy and analyzed the clinical variables of these patients. The prevalence rate of concurrent endometrial carcinoma in patients with endometrial hyperplasia was 26%. Those with atypical endometrial hyperplasia had a higher rate of coexisting endometrial carcinoma (54%). In addition to cytologic atypia, body mass index (BMI) was another risk factor. All the patients with concomitant endometrial carcinoma had at least one risk factor, but almost 50% of the cases in the non-endometrial group had no risk factors. Half of the women with cytological atypia and BMI > 25 had coexisting endometrial carcinoma. When patients are diagnosed with endometrial hyperplasia, surgical intervention should be performed in those with cytological atypia and higher BMI because of the possibility of coexisting endometrial carcinoma.

Clinicopathological Features in Endometrial Carcinoma Associated With Lynch Syndrome in China

To study the clinicopathological characteristics of Lynch syndrome-associated endometrial carcinoma in China. Twenty-seven patients who fulfilled Amsterdam criteria II were classified as having Lynch syndrome-associated endometrial carcinoma (group A), and 331 patients without a family history of cancer were classified as having sporadic endometrial carcinoma (group B). There were 81 malignancies in 27 families with Lynch syndrome-associated endometrial carcinoma, including colorectal cancer (24.7%), endometrial carcinoma (21.0%), and liver (12.3%), stomach (9.9%), lung (6.2%), and breast (6.2%) cancers. Mean age at the time of diagnosis was 49.7 years in group A and 56.3 years in group B (P = 0.004). Second primary cancers occurred in 33.3% of patients in group A and 5.1% in group B (P = 0.000). The most common second primary cancers were colorectal cancer (44%) and ovarian cancer (22%). The percentage of obese patients was higher in group A (P= 0.013). There was no difference between the 2 groups in incidence of diabetes mellitus or hypertension or in histological type and International Federation of Gynecology and Obstetrics stage. The 5-year survival rates for groups A and B were 96.2% and 79.6%, respectively. Prognosis for group A was better than for group B (P = 0.045). Some clinicopathological features of Lynch syndrome-associated endometrial carcinoma, such as early onset and multiple primary carcinomas are similar in the Chinese and American/European populations. However, the Chinese population had a unique family cancer distribution that included lung and breast cancers. Well-differentiated grade and good prognosis imply better biobehavior of Lynch syndrome-associated endometrial carcinoma in the Chinese population.

Clinical Value of Tumour Specific Growth Factor (TSGF) and Carbohydrate Antigen-125 (CA-125) in Carcinoma of the Endometrium

This study estimated the clinical value of tumour specific growth factor (TSGF) and carbohydrate antigen-125 (CA-125) in the diagnosis of endometrial carcinoma. Blood was collected from the peripheral and uterine veins of endometrial cancer patients, and serum TSGF and CA-125 levels were compared with those in uterine myoma patients (non-tumour controls) and normal women. Significantly higher levels of TSGF and TGSF-positive rates were observed in endometrial cancer patients versus non-tumour and normal controls. The sensitivity and specificity for detecting TGSF-positive rates in the endometrial carcinoma group were 64.9% and 62.5%, respectively. The TSGF levels in uterine blood were significantly higher than in peripheral blood and the TSGF-positive rate was also higher. The TSGF levels gradually increased with progression through the clinical stages and pathological grades of endometrial carcinoma. The sensitivity and specificity of combined TSGF and CA-125 for detecting endometrial cancer were 75.7% and 56.3%, respectively. It is concluded that there is an important correlation between serum levels of TSGF, CA-125 and endometrial cancer and that measurement of both TSGF and CA-125 combined would be of value in the diagnosis of endometrial carcinoma.

Expression and activation of insulin receptor substrate-1 in endometrial carcinoma

To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma. Sixty-three endometrial carcinoma (EC) patients, 21 endometrial atypical hyperplasia (AHE) patients and 22 normal control (NE) entered this study. Their clinical information were collected. Fasting serum C-peptide concentration was measured. Expression of IRS-1 in endometrium was examined by RT-PCR and western blot. Immunoprecipitation was used to measure the tyrosine phosphorylation of IRS-1. C-peptide concentration in EC group was higher than that in NE group [(3.2 +/- 1.1) vs (2.5 +/- 0.7) microg/L, P=0.007]. There were no significant differences in IRS-1 mRNA and protein expression among the three groups. Tyrosine phosphorylation of IRS-1 in EC group [(62 +/- 36) %] was higher than that in AHE and NE groups [(53 +/-34)% and (35 +/- 33)%; P=0.048, 0.002]. IRS-1 activation in AHE group was also higher than normal control (P=0.045). IRS-1 activation in endometrioid carcinoma [(69 +/- 33) %] was higher than that in other histological types [(34 +/- 31)%; t=2.300, P=0.025]. IRS-1 tyrosine phosphorylation was significantly higher in patients with advanced stage, high grade, deep myometrial invasion and pelvic lymph node metastasis. IRS-1 activation in endometrium was positively correlated with fasting serum C-peptide concentration (r=0.491, P=0.001). There is excessive activation of IRS-1 in endometrial carcinoma and atypical hyperplasia. Activation of IRS-1 in endometrial carcinoma is related with poor clinical-pathologic features and may be a prognostic predictor for this tumor. Over-activation of IRS-1 may be an intermediate event linking the hyperinsulinemia and endometrial carcinoma.

Histopathologic findings in women with postmenopausal bleeding: implication for endometrial thickness and circulating levels of sex steroid hormones

The aim of this study is to compare the relationship between estrone (E1), estradiol (E2), androgens, and prolactin blood levels on the one hand, and endometrial thickness and related histopathologic results on the other, in postmenopausal women admitted with uterine bleeding. The study was conducted in Gazi University School of Medicine, Obstetrics and Gynecology Clinic with a total of 128 patients. The study group consisted of 64 postmenopausal patients admitted with uterine bleeding, whereas the control group consisted of 64 healthy postmenopausal women. Vaginal sonography was performed to evaluate the endometrial thicknesses of the patients. Serum levels of free testosterone, androstenedione and estrone (E1) were determined by radioimmunoassay while serum estradiol (E2), prolactin, and dehydroepiandrosterone sulfate (DHEA-S) levels were evaluated by chemiluminescent method. The median age, duration of menopause, menopausal age and gravidity, and parity did not differ between women with postmenopausal bleeding and the control group (P > 0.05). However, DHEA-S level was lower (P < 0.05) and endometrial thickness was greater in the study group than the control group (P < 0.05). Furthermore, the study identified that median endometrial thickness of the patients in atrophic endometrium group was less than the endometrial hyperplasia and endometrium carcinoma group (P < 0.05). In the current study, all these hormones seemed to be indifferent between groups of endometrial cancer and other pathological results. Based on our results regarding the safe margin of endometrial thickness in women with postmenopausal bleeding, it seems justifiable to refrain from curettage in patients with an endometrium of < or =4 mm.

CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial carcinoma

The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for endometrial hyperplasia (EH) and endometrial carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and ECa and control subjects using allele-specific polymerase chain reaction-based method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with EH, indicating that persons carrying any Val allele are at increased risk for developing EH. In the ECa group, patients were also more likely to have CYP1A1 Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a statistically significant increase in relative risk association with any Val genotype between patients and controls, suggesting that individuals carrying any Val genotype are at increased risk for developing ECa. We concluded that variant alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility. Further studies with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.

CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial carcinoma

The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for endometrial hyperplasia (EH) and endometrial carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and ECa and control subjects using allele-specific polymerase chain reaction–based method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with EH, indicating that persons carrying any Val allele are at increased risk for developing EH. In the ECa group, patients were also more likely to have CYP1A1 Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a statistically significant increase in relative risk association with any Val genotype between patients and controls, suggesting that individuals carrying any Val genotype are at increased risk for developing ECa. We concluded that variant alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility. Further studies with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.

Pathologic features of endometrial carcinoma associated with HNPCC

Endometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas. Fifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma--women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI-high) secondary to methylation of MLH1 (n = 26). Nearly one-fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, 'undifferentiated' histology that was not observed in HNPCC or the young group. Data suggest a genotype-phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or 'undifferentiated' endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma.

Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study

The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naïve or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status ⩽2 entered the study. Docetaxel 70 mg m−2 was administered intravenously on day 1 of a 3-week cycle up to a maximum of six cycles. If patients responded well to docetaxel, additional cycles were administered until progressive disease or unacceptable toxicity occurred. Of 33 patients with a median age of 59 years (range, 39–74 years) who entered the study, 14 patients (42%) had received one prior chemotherapy regimen. In all, 32 patients were evaluable for efficacy, yielding an overall response rate of 31% (95% confidence interval, 16.1–50.0%); complete response and partial response (PR) were 3 and 28%, respectively. Of 13 pretreated patients, three (23%) had a PR. The median duration of response was 1.8 months. The median time to progression was 3.9 months. The predominant toxicity was grade 3–4 neutropenia, occurring in 94% of the patients, although febrile neutropenia arose in 9% of the patients. Oedema was mild and infrequent. Docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma, including those previously treated with chemotherapy; however, the effect was transient and accompanied by pronounced neutropenia in most patients.

A case-control study of uterine endometrial cancer of pre- and post-menopausal women.

Endometrial cancers are generally divided into at least two different pathogenetic types. One occurs from the proliferative endometrium, depending on continuous estrogen stimulation, while the other is not related to the stimulation and occurs from the atrophic endometrium of older post-menopausal women. In order to assess the risk factors for endometrial carcinoma (EC), a case-control study with 136 Japanese women having EC and with 376 healthy controls for ECs in Japan, together with an immunohistochemical analyses on p53, estrogen (ER) and progesterone receptors (PR) of EC patients was undertaken. Nulliparity, increased BMI, hypertension, diabetes mellitus, later age at menopause and personal cancer history were all seen predominantly in the EC group. Frequency of irregular menses, polycystic ovary syndrome (PCOS) and obesity in the EC patients under 40-year old was significantly higher than the control group. Immunohistochemical expressions of ER (P<0.05) and PR (P<0. 01) were more frequently recognized in the EC of the pre-menopausal than in the post-menopausal patients. On the other hand, p53 overexpression was detected in 27.2% of the post-menopausal EC group, while only found in 7.1% of the pre-menopausal EC group. These findings indicate that possible factors related to endometrial carcinogenesis are different between the pre- and post-menopausal EC patients. Namely, untreated ovarian dysfunction such as PCOS with unopposed estrogenic action in the endometrium may be associated with development and growth of EC in younger women, yet abnormality of p53 gene may be more concerned with the development of the post-menopausal EC, independently of sex steroid influence.