Endometrial carcinosarcomas have a different prognosis and pattern of spread compared to high-risk epithelial endometrial cancer

OBJECTIVE: The endometrial origin of uterine carcinosarcoma has recently been well established. The current study investigates whether uterine carcinosarcomas can be included in protocols on high-risk endometrial cancer, given the similarities in biologic behavior of both entities. METHODS: Pathological and surgical notes of patients diagnosed with grade 3 endometrioid, carcinosarcoma, serous and clear cell endometrial cancer subtypes were retrospectively analyzed with special attention to the spread pattern of the different subtypes. Information on site of relapse and time to recurrence was obtained. RESULTS: We traced 146 patients of which 9 patients were ineligible. Histological subtypes of the remaining 137 patients were as follows: 50 (37%) grade 3 endometrioid carcinoma, 54 (39%) serous or clear cell carcinoma (non-endometrioid carcinoma), and 33 (24%) carcinosarcomas. Distribution of early stage disease (I and II) was 67, 46, and 78% for grade 3 endometrioid, non-endometrioid, and carcinosarcoma, respectively. Although we could not trace differences in hematogenic and transperitoneal spread among the three subtypes, non-endometrioid and carcinosarcomas were more likely to spread to pelvic and paraaortic lymph nodes (P < 0.01). Using univariate analysis, both stage (P < 0.006, Wald statistic) and histological type appear to determine the outcome, whereas lymphovascular space infiltration (P < 0.25) and age (P < 0.07) were not significantly different between the three histological subtypes. Cox Regression multivariate analysis on 127 women suffering from the three histological subtypes suggested that both stage III-IV disease (P < 0.00001) and histological type (carcinosarcoma) (P < 0.003) were of prognostic significance [hazard ratio (CI 95%) were, respectively, 3.8 (2.1-7.0) and 3.2 (1.7-5.9)]. Analyzing cases limited to stage I-II endometrial cancer, 24/28 (86%) grade 3 endometrioid, 18/24 (75%) non-endometrioid, and 11/25 (44%) carcinosarcomas survived, suggesting a worse outcome for endometrial carcinosarcoma when compared to the other subtypes (P < 0.008, Log Rank). A higher incidence of pulmonary metastases explained the worse outcome for early stage carcinosarcoma (P < 0.006), whereas the incidence of liver metastasis, transperitoneal spread, or recurrences in lymph nodes or vagina were comparable between the three pathologic subtypes. CONCLUSIONS: Although endometrial carcinosarcoma originates from epithelial cancer, the intrinsic more aggressive tumor biology suggests that this subtype should not be incorporated in studies on high-risk epithelial endometrial cancer.     

Carcinosarcoma of the ovary: Natural history,patterns of treatment,and outcome

Objective

Ovarian carcinosarcomas (OCS) are rare tumors composed of both malignant epithelial and mesenchymal elements. We compared the natural history and outcomes of OCS to serous carcinoma of the ovary.

Methods

Patients with OCS and serous carcinomas registered in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2007 were analyzed. Demographic and clinical characteristics were compared using chi square tests while survival was analyzed using Cox proportional hazards models and the Kaplan–Meier method.

Results

A total of 27,737 women, including 1763 (6.4%) with OCS and 25,974 (93.6%) with serous carcinomas, were identified. Patients with carcinosarcomas tended to be older and have unstaged tumors (P < 0.0001). After adjusting for other prognostic factors, women with carcinosarcomas were 72% more likely to die from their tumors (HR = 1.72; 95% CI, 1.52–1.96). Five-year survival for stage I carcinosarcomas was 65.2% (95% CI, 58.0–71.4%) vs. 80.6% (95% CI, 78.9–82.2%) for serous tumors. Similarly, five-year survival for stage IIIC patients was 18.2% (95% CI, 14.5–22.4%) for carcinosarcomas compared to 33.3% (95% 32.1–34.5%) for serous carcinomas.

Conclusions

Ovarian carcinosarcomas are aggressive tumors with a natural history that is distinct from serous cancers. The survival for both early and late stage carcinosarcoma is inferior to serous tumors.     

PTEN mutations in uterine sarcomas

OBJECTIVE: Uterinesarcomas comprise three main types: carcinosarcomas, leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are highly aggressive neoplasms with a biphasic histology of carcinomatous and sarcomatous elements. It is now generally accepted that carcinosarcomas are biphasic tumors that have to be regarded as endometrial carcinomas where metaplasia occurs. Mutations of the PTEN tumor suppressor gene, located on 10q23, play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. Loss of heterozygosity of chromosome 10q has been reported in uterine leiomyosarcoma. Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas. METHODS: We examined 21 carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas using exon-by-exon polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: Overall 8.5% (4/47) of uterine sarcomas were found to harbor somatic PTEN mutations. Of these, approximately 17% (3/18) were carcinosarcomas with endometrioid-type carcinoma components and approximately 5% (1/21) were leiomyosarcomas. No mutations were detected in carcinosarcomas with nonendometrioid carcinoma components (0/3) and in endometrial stromal sarcomas (0/5). CONCLUSIONS: These data suggest that intragenic PTEN mutations are involved in the genesis of uterine carcinosarcomas with endometrioid-type carcinoma components but rarely contribute to the pathobiology of uterine leiomyosarcomas.     

Cervical carcinosarcoma: a case report

BACKGROUND: Carcinosarcomas are rare neoplasms of the female genital tract. They tend to be highly aggressive and are generally associated with a poor prognosis. Carcinosarcomas of the uterine cervix are extremely rare, with only approximately 35 cases previously reported in English. CASE: A 68-year-old woman presented with cervical carcinosarcoma. She remained without evidence of recurrent disease for 18 months after surgical resection and pelvic radiation treatment. CONCLUSION: In a review of all cases reported in the literature, it appears that cervical carcinosarcomas tend to present at an earlier stage than carcinosarcomas of the uterine corpus, therefore allowing early diagnosis and treatment. They may therefore be associated with a better overall prognosis than their counterparts in the corpus. Some studies have shown improved survival of patients of carcinosarcoma of the uterine corpus whose treatment included postoperative radiation and chemotherapy. Due to the better prognosis of cervical carcinosarcomas, we suggest studies to evaluate the role of aggressive, multimodal therapy, with the intent of obtaining a cure of cervical carcinosarcomas.     

Patterns of care,predictors, and outcomes of chemotherapy in elderly women with early-stage uterine carcinosarcoma: A population-based analysis

Objective

To examine the patterns of care, predictors, and impact of chemotherapy on survival in elderly women diagnosed with early-stage uterine carcinosarcoma.

Methods

The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify women 65 years or older diagnosed with stage I–II uterine carcinosarcomas from 1991 through 2007. Multivariable logistic regression and Cox-proportional hazards models were used for statistical analysis.

Results

A total of 462 women met the eligibility criteria; 374 had stage I, and 88 had stage II uterine carcinosarcomas. There were no appreciable differences over time in the percentages of women administered chemotherapy for early stage uterine carcinosarcoma (14.7% in 1991–1995, 14.9% in 1996–2000, and 17.9% in 2001–2007, P = 0.67). On multivariable analysis, the factors positively associated with receipt of chemotherapy were younger age at diagnosis, higher disease stage, residence in the eastern part of the United States, and lack of administration of external beam radiation (P < 0.05). In the adjusted Cox-proportional hazards regression models, administration of three or more cycles of chemotherapy did not reduce the risk of death in stage I patients (HR: 1.45, 95% CI: 0.83–2.39) but was associated with non-significant decreased mortality in stage II patients (HR: 0.83, 95% CI: 0.32–1.95).

Conclusions

Approximately 15–18% of elderly patients diagnosed with early-stage uterine carcinosarcoma were treated with chemotherapy. This trend remained stable over time, and chemotherapy was not associated with any significant survival benefit in this patient population.     

Prognostic factors for uterine cancer in reproductive-aged women

OBJECTIVE: To determine the prognostic factors that influence the survival of younger women diagnosed with uterine cancer. METHODS: Demographic and clinico-pathologic data were collected from the National Cancer Institute database between 1988 and 2001. Data were analyzed with Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: Of the 51,471 women diagnosed with uterine cancer in the study period, 2,076 (4.0%) patients were aged 40 years or younger, and 49,395 (96.0%) were older than 40. The mean age in the younger group was 35.6 years, compared with 65.2 years of the older group. The overall distribution by stage was stage I 75.4%, II 8.1%, III 6.7%, and IV 9.8%. Younger patients were more likely to be nonwhite (42.4% versus 18.3%, P<.001) and have stage I disease (79.2% versus 75.3%, P<.001), grade 1 lesions (47.6% versus 35.6%, P<.001), and sarcomas (15.9% versus 8.2%, P<.001) compared with their older counterparts. The overall 5-year disease-specific survival for younger patients was significantly better than that of older women (93.2% versus 86.4%, P<.001). On multivariable analysis, younger age, earlier stage, lower grade, nonblack race, endometrioid histology, and surgical treatment remained as significant independent prognostic factors for improved survival. CONCLUSION: This large population-based study demonstrates that patients 40 years and younger have an overall survival advantage compared with women older than 40 years, independent of other clinico-pathologic prognosticators. LEVEL OF EVIDENCE: III.     

Expression level of Wilms tumor 1 (WT1) protein has limited prognostic value in epithelial ovarian cancer: from the Danish "MALOVA" ovarian cancer study

OBJECTIVES: To determine the WT1 expression level in tumor tissues from 774 women with an epithelial ovarian tumor. Secondly, to evaluate whether WT1 tissue expression levels correlate with clinico-pathological parameters and finally to investigate the prognostic value of WT1 expression levels in ovarian cancer (OC) patients. METHODS: Using tissue array we analyzed the WT1 expression level in tissues from 186 women with Low Malignant Potential tumors (LMP) (160 stage I, 5 stage II and 21 stage III) and 560 OC patients (160 stage I, 60 stage II, 289 stage III and 51 stage IV). RESULTS: Using 10% as cut-off level for WT1 overexpression an overall of 19% LMPs and 17% carcinomas, respectively, were found positive. For both, a higher proportion of positive tumors was found in the serous subtype compared to other histological subtypes (p<0.0001). Kaplan-Meier survival analysis stratified by FIGO stage performed on cases using a 10% cut-off showed a shorter disease specific survival in patients with a positive WT1 expression in the tumor tissue. In a Cox survival analysis including 559 stage I to IV OC prognostic factors included FIGO stage (II vs. I: HR=2.74, 95% CI: 1.42-5.29; III vs. II: HR=2.23, 95% CI: 1.49-3.36; IV vs. III: HR=1.75, 95% CI: 1.25-2.44), residual tumor after primary surgery (HR=2.82, 95% CI: 1.87-4.26), age at diagnosis (HR=1.02, 95% CI: 1.01-1.03), histological grade 3 of tumor versus grade 1 (grade 2 vs. grade 1: HR=1.31, 95% CI: 0.95-1.81; grade 3 vs. grade 1: HR=1.51, 95% CI: 1.08-2.09) and other histological tumor types vs. serous (mucinous vs. serous: HR=0.91, 95% CI: 0.53-1.56; endometrioid vs. serous: HR=1.02, 95% CI: 0.69-1.50; other histological types vs. serous: HR=1.40, 95% CI: 1.01-1.95). WT1 expression (HR=1.22, 95% CI: 0.94-1.59) had statistically no significant independent impact on survival. CONCLUSION: In conclusion, based on our analyses we found that WT1 expression in clinical settings may be of limited prognostic value in Danish OC patients.     

子宫癌肉瘤41例临床病理分析

目的:探讨癌肉瘤的临床病理特征对预后的影响。方法:回顾分析2000年1月至2011年6月复旦大学附属妇产科医院收治的41例子宫癌肉瘤患者的临床病理特征,采用Kaplan-Meier生存分析和Cox回归多因素分析评价各因素对预后的影响,并比较肿瘤上皮成分及间叶成分与预后的关系。结果:患者的3年总生存率为57.5%,3年无瘤生存率为52.5%。单因素分析提示,FIGO分期(2009年)Ⅲ~Ⅳ期、深肌层浸润、宫颈间质侵犯、淋巴结转移与预后密切相关。Cox回归多因素分析提示,淋巴结转移(P=0.042,OR=3.375,95%CI为1.045~10.897)是影响预后的独立因素。肿瘤的上皮成分和间叶成分中p53表达无明显差异,上皮成分为非内膜样腺癌的总生存率低于内膜样腺癌(P=0.074);但不同的间叶成分预后无明显差异。结论:手术病理分期为晚期、病理提示深肌层浸润、宫颈间质侵犯、淋巴结转移等提示预后差;而淋巴结转移是影响预后的独立因素。癌肉瘤上皮成分和间叶成分可能为单克隆来源;上皮成分为影响肿瘤生物学行为的主导成分。     

Defective DNA mismatch repair and XRCC2 mutation in uterine carcinosarcomas

OBJECTIVES: A frameshift mutation in the double-strand breakage repair gene XRCC2 was identified in a mismatch repair (MMR) deficient cell line derived from a uterine carcinosarcoma. The frameshift mutation occurred in a mononucleotide run (poly-T tract), a target for strand-slippage mutation in MMR deficient tumors. We sought to determine if XRCC2 mutation is important to uterine carcinosarcoma tumorigenesis and whether the XRCC2 poly-T tract is a target for mutation in cells lacking MMR. METHODS: MSI-typing was used to assess the MMR status of 30 primary carcinosarcomas. The entire XRCC2 coding region was sequenced in all tumors. Single strand conformational variant (SSCV) analysis was used to screen for poly-T tract mutation in 50 endometrioid adenocarcinomas with defective MMR. RESULTS: Seven of 30 (23.3%) primary carcinosarcomas had an MSI-H phenotype. No XRCC2 coding mutations were identified in the 30 carcinosarcomas, and only one of the fifty MSI-H endometrioid adenocarcinomas had an XRCC2 poly-T tract mutation. CONCLUSIONS: Despite the high frequency of mismatch repair deficiency in carcinosarcomas, no XRCC2 poly-T tract frameshift mutations were identified in these tumors. The fact that only one of 50 additional MSI-H tumors had a frameshift mutation suggests that the XRCC2 poly-T tract is not a frequent target for defective MMR. The absence of coding sequence mutations in primary carcinosarcomas suggests that XRCC2 defects are unlikely to play a significant role in carcinosarcoma tumorigenesis.     

NAD dependent 11beta-hydroxysteroid dehydrogenase activity in human endometrium and endometrial tumors

BACKGROUND: The isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) types 1 and 2, regulated by ovarian steroids, catalyze the interconversion of glucocorticoids and their 11-keto metabolites. The role of these enzymes in malignancies of human endometrium is unknown. We compare NAD dependent 11beta-HSD (type 2) activity levels among normal human endometrium and endometrial carcinomas of differing grades and histologies. METHODS: NAD dependent 11beta-HSD activity was determined in endometrial tissue obtained from patients undergoing hysterectomy for benign or malignant disease (endometroid, serous and carcinosarcomas). Student's t test was utilized with p < 0.05 considered significant. Data are presented as mean +/- SD. RESULTS: NAD dependent 11beta-HSD activity was present in all endometrial samples. The activities were 0.61+/- 0.27 in normal (n = 9), 0.43 +/- 0.29 in endometrioid endometrial carcinoma (n = 14), 0.50 +/- 0.26 in uterine serous carcinoma (n = 6) and 0.25 +/- 0.37 in carcinosarcomas (n = 9). NAD dependent 11beta-HSD activity was lower in the carcinosarcoma group as compared to normal endometrial tissue (p = 0.03). CONCLUSIONS: NAD dependent type 2 11beta-HSD activity was demonstrated in all normal and endometrial tumors. Enzyme activity in endometroid and uterine serious carcinoma tumors was similar to enzyme activity in normal endometrium. In contrast, carcinosarcomas show significantly lower enzyme activity compared to normal tissue.     

Localization of the VEGF and angiopoietin genes in uterine carcinosarcoma

OBJECTIVE: Carcinosarcoma of the uterus is a highly aggressive tumor. However, the angiogenesis in this tumor remains unclear. This is the first study to examine the characteristics of angiogenesis in this tumor at the molecular level while also comparing the findings with those of high-grade endometrial carcinoma. METHODS: The expression of vascular endothelial growth factors (VEGF) and angiopoietins (Ang) genes were examined in 35 primary uterine carcinosarcomas as well as in 12 high-grade endometrial carcinomas by in situ hybridization. RESULTS: A strong expression of VEGF-A mRNA was significantly seen in carcinosarcomas compared to high-grade endometrial carcinomas. Interestingly, in uterine carcinosarcoma, VEGF-A mRNA was more strongly expressed in the carcinoma cells than in the sarcoma cells. In addition, a decrease in the VEGF-A mRNA expression was found in the transitional areas between carcinomatous and sarcomatous elements in most carcinosarcomas evaluated. Moreover, the Ang-2 mRNA expression was significantly seen in the vasculature adjacent to the periphery of the carcinoma cells in most carcinosarcomas, in comparison to that of endometrial carcinomas. CONCLUSIONS: A high angiogenic activity in uterine carcinosarcoma was shown, in comparison to that of endometrial carcinoma. Tumor angiogenesis in uterine carcinosarcoma might be chiefly influenced by VEGF-A in the carcinoma cells, in cooperation with Ang-2 in the surrounding microvessels, however, this is not fully usually the case in sarcoma cells.     

Uterine malignant mixed mullerian tumors should not be included in studies of endometrial carcinoma

OBJECTIVE: Uterine mixed malignant mullerian tumors (MMMT) have traditionally been excluded from clinical trials of endometrial cancer because of a belief that they are more correctly included in the sarcoma category. Recently, investigators have suggested that uterine MMMTs are actually dedifferentiated epithelial tumors and should be treated as such. The current study was undertaken to compare outcomes, stage for stage, of uterine MMMT with poor prognosis endometrial adenocarcinomas. METHODS: Cases of MMMT from 1996 to 2004 were identified from the Tumor Registry after IRB consent was obtained. Retrospective chart review was performed. Cases were matched by age, stage, performance status, and surgical procedure to controls consisting of grade 3 endometrioid, papillary serous, and clear cell endometrial carcinomas from the same time period. Overall survival was compared using the Log-Rank test. RESULTS: 68 patients with MMMT were identified. 23 were excluded due to incomplete records. Patients with MMMT ranged in age from 51 to 95 years (mean 75.3 years). Approximately half of the patients (53%) had stage III or IV disease. Of the controls, 31 (69%) had grade 3 endometrioid, 11 (24%) papillary serous, and 3 (7%) clear cell carcinoma. Median overall survival for all patients with MMMT was significantly shorter than for controls, 18 months (range 0.5-72) versus 36 months (range 0.5-123) (P = 0.02). Patients with early stage disease (stage I or II) had shorter median survival than controls, 26 months (range 3-7) vs. 95 months (range 4-123) (P = 0.003). There was no difference in median survival when comparing advanced disease (stage III or IV) to matched controls, 15 months (range 0.5-70) vs. 19 months (range 0.5-100) (P = NS). CONCLUSIONS: Patients with uterine MMMT have a poorer prognosis than those patients with high grade epithelial tumors, especially for those with early stage disease. Given the discrepancy in survival, these patients should not be included in studies of endometrial carcinoma. Further investigations are necessary to identify factors to improve survival of these patients.     

Obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas

OBJECTIVE: To determine the rate, obstetric characteristics and perinatal outcome of pregnancies with uterine leiomyomas. STUDY DESIGN: A population-based study comparing all singleton deliveries between the years 1988 and 1999 in women with and without uterine leiomyomas was performed. Patients lacking prenatal care were excluded from the analysis. Multivariable analysis, adjusting for possible confounders, such as maternal age, parity and gestational age, was performed to investigate associations between uterine leiomyomas and selected outcomes. RESULTS: There were 105,909 singleton deliveries with 690 (0.65%) complicated by uterine leiomyomas during the study period. Using a multivariable analysis, the following conditions were significantly associated with uterine leiomyomas: nulliparity (odds ratio [OR]=4.0, 95% confidence interval [CI] 3.3-4.7, P<.001), chronic hypertension (OR=1.9, 95% CI 1.6-2.4, P<.001), hydramnios (OR=1.5, 95% CI 1.2-2.0, P<.001), diabetes mellitus (OR=1.4, 95% CI 1.1-1.7, P=.001) and advanced maternal age (OR=1.2, 95% CI 1.1-1.2, P<.001). Higher rates of perinatal mortality (2.2% vs. 1.2%, OR=1.8, 95% CI 1.1-3.2, P<.001) were found in the uterine leiomyoma group as compared to the control group. While adjusting for maternal age, parity, gestational age and malpresentation, pregnancies with uterine leiomyomas had higher rates of cesarean deliveries (OR=6.7, 95% CI 5.5-8.1, P<.001), placental abruption (OR=2.6, 95% CI 1.6-4.2, P<.001) and preterm deliveries (<36 weeks' gestation, OR=1.4, 95% CI 1.1-1.7, P=.009) as compared to pregnancies without uterine leiomyomas. Conversely, no significant differences were noted regarding perinatal mortality (OR=1.4, 95% CI 0.7-2.8, P=.351) after controlling for maternal age, parity and gestational age using a multivariable analysis. CONCLUSION: Uterine leiomyomas increase the risk of adverse pregnancy outcomes, thus emphasizing the importance of appropriate intrapartum management of these high-risk pregnancies.     

Carcinosarcoma of the ovary: a case-control study

Introduction

Carcinosarcoma of the ovary is a rare tumor with a grim prognosis. Chemotherapy for these tumors is chosen according to guidelines established for epithelial ovarian cancer (EOC). The purpose of this study is to compare response to chemotherapy and survival in patients with advanced stage carcinosarcoma of the ovary.

Methods

We identified women with advanced carcinosarcoma of the ovary who underwent first-line platinum and taxane-based chemotherapy. Each case was matched to two women with serous EOC. Cases and controls were matched by age, stage, and year of diagnosis. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model.

Results

Fifty women treated with first line platinum and taxane-based chemotherapy had advanced carcinosarcoma of the ovary and were selected as cases. The response rates to chemotherapy for cases and controls were 62% and 83% (P = 0.03), respectively. Median progression-free survival was 11 months (95% CI, 8 to 14 months) versus 16 months (95% CI, 12 to 21 months; P = 0.02) and median overall survival was 24 months (95% CI, 18 to 29 months) versus 41 months (95% CI, 33 to 49 months; P = 0.002) for cases and controls, respectively.

Conclusion

Patients with advanced carcinosarcoma of the ovary have a poorer response to platinum and taxane-based first-line chemotherapy and worse survival, compared to patients with serous EOC. Aggressive surgical treatment may play an important role. However, other alternative systemic therapeutic approaches should be sought for patients with carcinosarcoma of the ovary.     

The outcomes of 27,063 women with unstaged endometrioid uterine cancer

BACKGROUND: Over two-thirds of patients with endometrioid uterine cancer in the Surveillance, Epidemiology and End Results program from 1988 to 2001 did not undergo a lymphadenectomy. These patients were compared to those who had a lymphadenectomy. METHODS: Kaplan-Meier methods and Cox proportional hazards regression analyses were employed. RESULTS: Of 39,396 women (median age: 65 years) with endometrioid uterine cancers, 12,333 (31.3%) underwent surgical staging procedures including lymphadenectomy. The remainder did not receive a lymphadenectomy. The 5-year disease-specific survival (DSS) of stages I-IV women who underwent lymphadenectomy were 95.5%, 90.4%, 73.8%, and 53.3% compared to 96.6%, 82.2%, 63.1%, and 26.9% in those without lymphadenectomy (p>0.05 for stage I; p<0.001 for stages II-IV). In stage I patients, those who did not receive lymphadenectomy had a higher proportion of tumors with grade 1 histology and/or disease limited to the endometrium compared to those who underwent lymphadenectomy (54.8 % vs. 34.7%; p<0.001, grade 1 disease; 26.6% vs. 15.9%; p<0.001, no myometrial invasion). In patients with stage I grade 3 disease, those who underwent lymphadenectomy had a better 5-year DSS than those without lymphadenectomy (90% vs. 85%; p=0.0001); however, no benefit for lymphadenectomy was seen for patients with stage I grade 1 (p=0.26) and grade 2 (p=0.14) disease. On multivariable analysis, younger age, Caucasian race, early-stage disease, low grade histology, and lymphadenectomy were independent prognostic factors for improved disease-specific survival. CONCLUSIONS: Our data suggest that lymphadenectomy is associated with an improved survival in stage I grade 3 and more advanced endometrioid uterine cancers.     

Association between uterine serous carcinoma and breast cancer

OBJECTIVE: Endometrial cancer and breast cancer are two common malignancies found in women. As a result of estrogen dependency, an association is thought to exist between these entities. This study was undertaken to determine if the endometrial carcinomas, which develop in women with a history of breast cancer, were more likely to be of the endometrioid or the serous histology, which is generally considered non-estrogen-dependent. METHODS: A retrospective chart review was conducted for the years 1984-2001. All women who were diagnosed at our institution with endometrial carcinoma were identified. The women who also had a prior history of breast cancer were identified and comprise the cohort for this study. Information regarding age at diagnosis, tumor stage, histologic subtype, and tamoxifen exposure were recorded and analyzed. RESULTS: About 1166 women were diagnosed with endometrial cancer during the study period, of whom 54 (4.6%) had a pre-existing diagnosis of breast cancer. Of the 54 women in this study, 41 had tumors of the endometrioid histology and 13 had a tumor of the serous subtype. There was no difference with regards to median age at the time of diagnosis or years of tamoxifen exposure. Women with breast cancer were more likely to develop uterine serous carcinoma (USC) as compared to one of endometrioid histology (OR 2.6; 95% CI 1.29-5.23). CONCLUSIONS: Women with breast cancer who subsequently developed endometrial cancer exhibited a 2.6-fold increased risk of developing a USC as compared to an endometrioid carcinoma. These findings suggest that there may be an underlying genetic predisposition linking breast cancer and USC.     

Black race independently predicts worse survival in uterine carcinosarcoma

Objective

GOG 150 suggested that Black women had worse survival compared to White women with uterine carcinosarcoma. Our objective was to compare treatment and survival outcomes between Black and White women at a National Comprehensive Cancer Network (NCCN) cancer center serving a diverse racial population.

Methods

An IRB approved retrospective cohort study of uterine carcinosarcoma patients diagnosed between 2000 and 2012 was performed. Survival was compared by race and stratified by stage. Median progression free and overall survival (PFS and OS) were calculated using Kaplan–Meier estimates and compared with the log-rank test. Multivariate survival analysis was performed with Cox proportional hazards model.

Results

158 women were included: 93 (59%) were Black and 65 (41%) were White. 95 (60%) had early stage disease and 63 (40%) had advanced stage disease. Black women had a shorter PFS (7.9 vs. 14.2 months, p < 0.001) and OS (13.4 vs. 30.8 months, p < 0.001). There was no difference in survival between Black and White women with advanced stage disease (OS 8.5 vs. 11.8, p = 0.18). However, PFS and OS were worse in Black women compared to White women with early stage disease (PFS 13.6 vs. 77.4, p = 0.001), (OS 25.4 vs. 94.7, p = 0.003). On multivariate analysis accounting for age, stage, BMI, and adjuvant treatment, Black race remained independently associated with risk of death (HR 2.0; 95% CI 1.25–3.23).

Conclusions

Black women with uterine carcinosarcoma have worse survival compared to White women despite similar patient and treatment characteristics. This difference is largely due to differences in survival in early stage disease.     

Outcome of uterine clear cell carcinomas compared to endometrioid carcinomas and poorly-differentiated endometrioid carcinomas

OBJECTIVES: Our aim was to compare the survival between patients with clear cell carcinoma (CC) and patients with endometrioid carcinoma (EC). METHODS: Through the population-based Geneva Cancer Registry, we identified 1,380 resident women diagnosed with uterine cancer between 1970 and 2000. We excluded those with papillary serous endometrial carcinoma and uterine sarcomas. We categorized patients as CC (n = 32, 2.8%) or EC (n = 1,145, 97.2%). Uterine cancer-specific survival rates were calculated by Kaplan-Meier analysis. We used Cox proportional hazards analysis to compare uterine cancer mortality risks between groups, and adjusted these risks for other prognostic factors. RESULTS: CC patients presented with a more advanced stage at diagnosis than EC patients (p = 0.002). Compared to women with EC, women with CC had a significantly greater risk of dying from their disease (hazard ratio [HR] 2.9, 95% confidence interval (95% CI) 1.7-4.9). After adjustment for age, stage and adjuvant chemotherapy, the risk of dying from uterine cancer was still significantly higher for CC patients (HR 2.0, 95% CI 1.2-3.4). By univariate analysis, the risk of dying of endometrial cancer was not significantly higher in CC patients than in patients with poorly-differentiated EC (HR 1.3, 95% CI 0.7-2.3). CONCLUSION: This population-based investigation shows that patients with CC have a poorer outcome than those with EC. Studies to determine the role of adjuvant treatment in CC patients are needed.     

Cancer of the uterine corpus among Hispanic women living in the United States: patterns of staging, diagnosis, and primary treatment

OBJECTIVES: To evaluate the demographic characteristics, clinico-pathological features, and patterns of care of uterine cancer among Hispanic women living in the United States. METHODS: The National Cancer Institute (NCI)'s Surveillance, Epidemiology, and End Results Program (SEER), was used to identify 1618 Hispanic, 17,814 non-Hispanic white (NHW), and 1477 non-Hispanic black (NHB) women diagnosed with primary carcinoma of the uterus during 1996-2000. Data derived from hospital registries was analyzed, for differences in case presentation, staging, and primary treatment by race/ethnicity and age. Statistical analysis was performed using the IBM PC packages, Stata, and the SAS system. RESULTS: Hispanic women were statistically significantly more likely to present with uterine cancer at a younger age compared to non-Hispanic groups. Hispanic women with early stage disease (stage I-II) were also statistically significantly more likely to be younger than 55 years at the time of diagnosis (NHW: OR=0.40, 95% CI: 0.35-0.45; P = 0.0000, NHB: OR=0.45, 95% CI: 0.38-0.55; P=0.0000). Hispanics were statistically significant less likely than NHB to present with advanced stage disease, high tumor grade, and receive radiation therapy for uterine cancer. CONCLUSIONS: Hispanic women are more likely to be diagnosed with uterine cancer at a younger age than other ethnic groups. The etiologic factors related to this presentation have yet to be precisely defined. Additional epidemiological and demographic studies, addressing such factors as body mass index and other medical co-morbidities, are needed to identify opportunities for improved cancer prevention and control in this population of women.     

Changes in fetal heart rate and uterine patterns associated with uterine rupture

OBJECTIVE: To determine changes in fetal heart rate (FHR) and uterine patterns preceding complete uterine rupture. STUDY DESIGN: FHR and uterine patterns of 50 women with uterine rupture were compared with 601 tracings of controls without scarred uteri. Tracings were interpreted using the National Institute of Child Health and Human Development Research Planning Workshop guidelines. RESULTS: Interobserver and intraobserver agreements of FHR and uterine tracings in the uterine rupture group were excellent (kappa of .96 for both variables). Comparing tracing patterns during the first stage, higher rates of severe fetal bradycardia (4.0% vs. 1.0%, P = .064), fetal tachycardia (8.0% vs. 2.3%, P = .042), reduced baseline variability (24.0% vs. 12.5%, P = .021), uterine tachysystole (10.0% vs. 0.8%, P < .001) and disappearance of contractions (6.0% vs. 0, P < .001) were noted among patients with uterine rupture as compared to the controls. During the second stage of labor, patients with uterine rupture had significantly higher rates of reduced baseline variability (47.8% vs. 7.7%, P < .001), severe variable decelerations (26.1% vs. 6.4%, P = .004), uterine tachysystole (22.0% vs. 0.5%, P < .001) and disappearance of contractions (13.0% vs. 0, P < .001). Using a backward, stepwise multiple logistic regression model, severe fetal bradycardia (OR = 8.2, 95% CI 2.2-31.0, P = .002) and uterine tachysystole (OR = should alert the 8.0, 95% CI 1.7-37.9, P = .008) were found to be independent patterns preceding uterine rupture during the first stage of labor. Likewise, during the second stage, reduced baseline variability (OR = 4.2, 95% CI 1.4-12.3, P = .009) and uterine tachysystole (OR = 42.3, 95% CI 10.6-168.3, P < .001) were independently associated with uterine rupture in another multivariable analysis. CONCLUSION: Abnormal monitor patterns among women presenting with risk factors for uterine rupture, specifically uterine tachysystole, reduced baseline variability and severe bradycardia, should act as warning signs to the obstetrician.