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Introduction: From among gynecologic cancers, epithelial ovarian cancer (EOC) is the leading cause of mortalities due to gynecologic cancers in the United States, constituting 3.6% of all types of gynecologic cancers. A major reason for this poor treatment outcome is that most EOC patients are frequently diagnosed in advanced stages of the disease. A standard management for EOC patients involves a primary cytoreductive surgery followed by adjuvant chemotherapy if needed. However, primary breast cancer is one of the most common malignancies in women, and metastasis of other cancers to the breast is relatively rare. Case Presentation: Here, we report the case of a 70-year-old patient who five years ago had undergone laparotomy due to post-menopausal bleeding, adnexal mass, and elevated CA125. With the diagnosis of metastatic papillary serous, she underwent primary cytoreductive surgery and adjuvant chemotherapy. Regarding the history of ovarian cancer diagnosed five years ago, and further examination of this suspicious lymph node, and rejection of the risk of breast cancer, the patient was examined for the risk of metastasis. In biopsy and immunohistochemistry study, metastatic lymph node was diagnosed with the origin of epithelial ovarian cancer, and the patient was treated with beta-taxol + carboplatin, and the size of the axillary lymph node shrank. Conclusion: Regarding the unusual nature of recurrence of ovarian cancer as isolated axillary lymph node involvement, this report emphasizes the importance of considering metastasis in the axilla and its differential diagnosis from breast cancer in patients with a history of ovarian cancer, since prognoses and treatments are different for each diagnosis.

To compare the survival of women with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CC) to those with grade 3 endometrioid uterine carcinoma (G3EC). Demographic, pathologic, treatment, and survival information were obtained from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Data were analysed using Kaplan-Meier and Cox proportional hazards regression methods. Of 4180 women, 1473 had UPSC, 391 had CC, and 2316 had G3EC cancers. Uterine papillary serous carcinoma and CC patients were older (median age: 70 years and 68 vs 66 years, respectively; P

Abstract Purpose We evaluated the utilization of vaginal brachytherapy (BT) and the resulting impact on survival in stage IA endometrial cancer of clear cell (CC), papillary serous (PS), and carcinosarcoma (CS) histology. Methods Patients with uterine cancer diagnosed from 2004 to 2015 were identified from the National Cancer Database. Patients underwent hysterectomy, showing FIGO stage IA disease with CC, PS, or CS histology. Logistic regression was used to evaluate predictors of BT utilization and to generate propensity scores. Survival was compared using log-rank test and Cox proportional hazards modeling, with propensity score adjustment. Results We identified 5711 patients who underwent hysterectomy showing FIGO pT1a, N0 or NX endometrial cancer with CC, PS, or CS histology, of which 29.5% received BT. Multivariate predictors of increased receipt of BT were identified. With a median follow-up of 3.3 years, 3-year overall survival (OS) was 87% for those receiving BT versus 78% for those without (p < 0.001). A survival benefit to BT was maintained across histologies. Similar results were seen whether tumor was confined to endometrium or had <50% myometrial invasion. On multivariate analysis, receipt of BT was associated with increased survival (hazard ratio [HR] 0.75, 95% confidence interval 0.65–0.87, p < 0.001). The benefit of BT persisted after propensity score adjustment (HR 0.76, p < 0.001). Conclusions In this cohort of women with stage IA endometrial cancer of unfavorable histology, the use of BT was associated with improved survival. In this study, 29.5% of patients in our cohort received BT. Highlights • Adjuvant brachytherapy is associated with improved survival in stage IA endometrial cancer of unfavorable histology. • Utilization of brachytherapy in this clinical scenario is rare currently, at 29.5% of patients from a national cohort. • Adjuvant chemotherapy improves survival in most situations, but may not be beneficial in clear cell patients. • Adjuvant external beam radiation is not routinely beneficial. It may help in those with additional risk factors. [ABSTRACT FROM AUTHOR]

Objective High grade histologies of endometrial carcinomas portend a worse prognosis. Previous randomized, prospective studies examining the role of radiation have excluded endometrial cancer patients with FIGO IB with high risk histologies (clear cell, papillary serous, and Grade 3 endometrioid adenocarcinoma). Methods We retrospectively identified 51 patients who underwent a hysterectomy for a FIGO IB endometrial carcinoma with clear cell, papillary serous or Grade 3 endometrioid adenocarcinoma histology. Adjuvant radiation therapy was delivered in 44 of 51 patients (86%). We assessed pelvic control, vaginal control, and overall survival using Kaplan Meier estimate and the log rank test. We completed univariate analysis. Results The 5-year vaginal control rate in patients without and with adjuvant radiation therapy was 67% and 93.3%, respectively (p = 0.0066). At 5-years, the pelvic control rate in patients without and with adjuvant radiation therapy was 0% and 81.5%, respectively (p = 0.0003). At 5-years, the overall survival was 80% in patients who had adjuvant radiation compared to 21.4% in patients who did not have adjuvant radiation (p = 0.0026). Radiation therapy was the only studied variable that was associated with pelvic control. Radiation therapy, advanced age and pelvic lymphadenectomy were associated with overall survival. Conclusions Adjuvant radiation therapy in patients with FIGO IB endometrial carcinoma with high risk histologies was associated with improved vaginal control, pelvic control, and overall survival. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate our institutional experience combining carboplatin-paclitaxel (C/T) chemotherapy with high-dose-rate (HDR) intra-vaginal brachytherapy (IVB) following comprehensive surgical staging in localized uterine serous carcinoma (USC). Material and methods: Institutional chart review identified 56 patients with FIGO 2009 stage I-II USC treated between 2000-2010. Patients underwent total hysterectomy, bilateral salpingo-oopherectomy, and comprehensive surgical staging including pelvic and para-aortic lymph node dissection, omentectomy, and peritoneal cytology. Chemotherapy was 6 cycles of C/T, and the IVB dose was 14 Gy in 2 fractions, prescribed to 0.5 cm from the cylinder surface. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS) and overall survival (OS). Results: The median follow-up time was 49 months (range: 9-145). The 5-yr RFS and OS were 85% and 93%, respectively. In all cases of recurrence (n = 8), the first site of failure was extra-pelvic. There were no isolated vaginal recurrences, however, there was one vaginal apex recurrence recorded at 19 months in a patient with simultaneous lung metastases. Thus, the 2-year vaginal RFS was 98%. Conclusions: Excellent vaginal/pelvic control rates were observed. Further study of HDR brachytherapy dose and fractionation in combination with chemotherapy is worthwhile. [ABSTRACT FROM AUTHOR]

Purpose: To report outcomes following adjuvant high-dose-rate vaginal brachytherapy (VBT) with or without chemotherapy for high-intermediate risk (HIR) and high-risk, early stage endometrial cancer as defined in Gynecologic Oncology Group trial 0249. Material and methods: From May 2000 to January 2014, 68 women with HIR and high-risk endometrial cancer underwent surgical staging followed by VBT. Median VBT dose was 21 Gy delivered in three fractions prescribed to 0.5 cm depth. Paclitaxel 175 mg/m2 and carboplatin area under the curve 6 was administered every 21 days in sequence with VBT. Actuarial survival estimates were calculated using the Kaplan-Meier method. Results: Patient demographics included a median age of 66 years (range: 36-91) and stages IA (49%), IB (38%), and II (13%), respectively. Thirty-one (46%) patients had HIR disease with endometrioid histology, and 33 (48%) patients had serous or clear cell histology. Thirty-seven (54%) patients received a median 3 cycles (range: 3-6) of chemotherapy in addition to VBT, and 65 patients (96%) completed all prescribed therapy. During a median follow up of 33.1 months (range: 4.0-161.7), four patients have recurred, including one vaginal recurrence. The 3-year estimates of vaginal, pelvic, and distant recurrences were 1.9%, 2.4%, and 9.1%, respectively. The 3-year rates of disease-free and overall survival were 87.7% and 93.9%, respectively. Conclusions: Early outcomes with adjuvant VBT with or without chemotherapy demonstrate high rates of vaginal and pelvic control for women with HIR disease. Early vaginal and pelvic relapses in high-risk patients suggest that pelvic external beam radiotherapy is warranted in this subgroup, but additional data from large phase III trials is warranted. [ABSTRACT FROM AUTHOR]

Background Type II (papillary serous and clear cell) endometrial carcinoma (EC) is a rare subgroup and is considered to have an unfavorable prognosis. The purpose of this retrospective analysis was to elucidate the meaning of adjuvant radiotherapy (RT) for clinical outcome and to define prognostic factors in these patients (pts). Methods From 2004-2012 forty-two pts with type II EC underwent surgery followed by adjuvant RT at our department. Median age was 72 years. The majority were early stage carcinomas (FIGO I n = 27 [64.3%], FIGO II n = 4 [9.5%], FIGO III n = 11 [26.2%]. Seven pts (16.7%) received adjuvant chemotherapy (ChT). Pts were treated with external beam radiotherapy (EBRT) and brachytherapy (IVB) boost. Results Five-year local recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) were 85.4%, 78%, 64.5% respectively. LRFS was better with lower pT stage, without lymphangiosis (L0), without haemangiosis (V0) and negative resection margins (R0). DMFS was prolonged in lymph node negatives (N0), L0, V0 and R0. OS was improved in younger pts, N0, L0, V0 and after lymphadenectomy (LNE). Multivariate analysis revealed haemangiosis (V1) as the only independent prognostic factor for OS (p = .014) and DMFS (p = .008). For LRFS pT stage remained as an independent prognostic factor (p = .028). Conclusions Adjuvant RT with EBRT/IVB ensures adequate local control in type II EC, but control rates remain lower than in type I EC. A benefit of additional adjuvant ChT could not be demonstrated and a general omission of EBRT cannot be recommended at this point. Lymphovascular infiltration and pT stage might be the best predictive factors for a benefit from combined local and systemic treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer. Methods: We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival. Results: The median age of the cohort was 67years old with a mean follow up 152months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local–regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local–regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p =0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p =0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value=0.018) was associated with a significant increase in local relapse free survival. Conclusions: Adjuvant radiation therapy was significantly associated with an improvement in local–regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate patterns of relapse in early stage uterine papillary carcinoma (UPSC) patients receiving adjuvant intravaginal radiotherapy (IVRT) with or without chemotherapy. Methods: From 1/1996 to 12/2010, 77 women with stage I–II UPSC underwent surgery followed by IVRT (median 21Gy). Stage IA patients without residual disease at surgery were excluded. IVRT and chemotherapy (carboplatin/taxane) was given to 61 (79%) patients and IVRT alone to 16 (21%). The median follow-up was 62months for surviving patients. Results: Of the 77 patients, 11 (14%) relapsed as follows: vaginal 2 (3%), pelvic 5 (6%), para-aortic 5 (6%), peritoneal 6 (8%), and other distant sites 8 (10%). Of the 5 pelvic relapses, 2 were isolated and were salvaged. In those treated without chemotherapy, only 1/16 developed recurrence (mediastinal). The 5-year vaginal, pelvic, para-aortic, peritoneal, and distant recurrence rates were 2.7% (C.I. 0–6.2%), 5.8% (C.I. 0.6–11.0%), 5.4% (C.I. 0.6–10.1%), 5.3% (C.I. 0.5–10.1%) and 6.6% (C.I. 1.4–11.8%), respectively. The 5-year disease-free survival (DFS), and overall survival (OS) were 88% (C.I. 81–95%), and 91% (C.I. 84–97%), respectively. The only predictor of worse 5-year pelvic control was stage (96.2% stage IA vs 87.7% for stage IB-II, p =0.043). Conclusions: In stage I–II UPSC patients who predominantly receive adjuvant chemotherapy, IVRT as the sole form of adjuvant RT provides excellent locoregional control. The risk of isolated pelvic recurrence is too low to warrant routine use of external pelvic RT. [Copyright &y& Elsevier]

Abstract: Objective: To investigate clinical outcomes of stage IA uterine papillary serous (UPSC) and clear cell carcinoma (CC) arising from or associated with a polyp. Methods: From 1995 to 2011, we identified 51 cases of stage IA UPSC (67%), CC (8%) or mixed histology (26%) endometrial cancer. Of these, 32 had disease confined to polyp (seven with no residual disease after hysterectomy), 14 had surface spread, 1 had myometrial invasion (MMI) and 4 had both. The majority of patients did not receive adjuvant therapy (80%). Patients given adjuvant treatment (either platinum-based chemotherapy alone, radiation alone, or a combination of the two) had incomplete staging or abnormal cytology. Results: At mean follow-up of 58.3months, only 4 patients had progressed, via pelvic adenopathy, carcinomatosis or both. There were no vaginal cuff recurrences. Kaplan–Meier 5year estimates were pelvic control of 92.1%, disease-free survival 93% and OS 80.6%. Only 9% (3/32) of cases confined to polyp progressed. One responded to salvage chemoradiation, but two died despite salvage. Only 5% (1/19) of cases with surface and MMI progressed. On univariate analysis, only MMI and abnormal/positive cytology were significantly associated with increased pelvic recurrence (MMI p =0.0059, cytology p =0.0036) and worse DFS (MMI p =0.0018, cytology p =0.0054). Two patients given adjuvant treatment developed new gynecologic malignancies. Conclusion: In our study, patients with limited UPSC/CC disease involving a polyp who have complete workup did well without adjuvant therapy, with recurrence rates similar to UPSC/CC stage IA disease. Late and extensive pelvic relapses may occur in the few who do relapse. [Copyright &y& Elsevier]

Abstract: Objective: To prospectively evaluate tumor control, survival, and toxic effects in patients with International Federation of Gynecology and Obstetrics (1988) stage I–IIIA papillary serous carcinoma of the endometrium treated with concurrent chemoradiation and adjuvant chemotherapy. Methods: Thirty-two patients were enrolled from October 2001 through July 2009. Patients underwent full surgical disease staging and postoperative concurrent weekly paclitaxel (50mg/m2) and pelvic RT to 45Gy plus a vaginal cuff boost followed by 4cycles of adjuvant paclitaxel (135mg/m2). Results: Thirty patients (94%) were evaluable (3 with stage IA disease, 11 IB, 3 IC, 1 IIB, and 12 IIIA). Eighteen patients (60%) received all 5 planned courses of concurrent chemotherapy, 10 (33%) received 4 courses, and 2 (7%) received 3 courses. All 30 patients received RT; 27 (90%) received the full dose, 2 received 43.2Gy, and 1 received 39.6Gy owing to toxic effects. Twenty-three patients (77%) completed all 4cycles of adjuvant paclitaxel, 3 (10%) completed 3cycles, 2 (7%) completed 2cycles, and 2 received no adjuvant therapy. Overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 93%, 87%, and 87%, respectively, at 2years and 85%, 83%, and 87%, respectively, at 5years. Six patients developed (20%) grade 3/4 toxicities from the treatment. Four patients (13%) had grade 3 or more severe bowel complications and two patients developed symptomatic pelvic fractures. Conclusions: Treatment with concurrent paclitaxel and pelvic RT followed by 4 courses of systemic paclitaxel produced favorable results in patients with surgically staged I–III UPSC. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of this study is to report our single-institution experience with concurrent adjuvant intravaginal radiation (IVRT) and carboplatin/paclitaxel chemotherapy for early stage uterine papillary serous carcinoma (UPSC). Methods: From 10/2000 to 12/2009, 41 women with stage I–II UPSC underwent surgery followed by IVRT (median dose of 21Gy in 3 fractions) and concurrent carboplatin (AUC=5–6) and paclitaxel (175mg/m2) for six planned cycles. IVRT was administered on non-chemotherapy weeks. The Kaplan–Meier method was used to estimate survival, and the log-rank test was used for comparisons. Results: Median patient age was 67years (51–80years). Surgery included hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and paraaortic lymph node sampling. FIGO 2009 stage was IA in 73%, IB in 10%, and II in 17%. Histology was pure serous in 71% of cases. Thirty-five patients (85%) completed all planned treatment. With a median follow-up time of 58months, the 5-year disease-free (DFS) and overall survival (OS) rates were 85% (95%CI, 73–96%) and 90% (95%CI, 80–100%). The 5-year pelvic, para-aortic, and distant recurrence rates were 9%, 5%, and 10%, respectively. There were no vaginal recurrences. Of the 4 pelvic recurrences, 2 were isolated and were successfully salvaged. Patients with stage II disease had lower DFS (71% vs. 88%; p=0.017) and OS (71% vs. 93%; p=0.001) than patients with stage I disease. Conclusions: Concurrent adjuvant carboplatin/paclitaxel chemotherapy and IVRT provide excellent outcomes for early stage UPSC. Whether this regimen is superior to pelvic radiation will require confirmation from the ongoing randomized trial. [Copyright &y& Elsevier]

CXCL12 is a chemotactic cytokine that has pro-metastatic functions in several malignancies through interactions with its receptor, CXCR4. CXCL12 is an estrogen-regulated gene, and notably, estrogen is a major risk factor for endometrial cancer (EC) development. As few studies examine concurrent CXCL12, CXCR4, and estrogen receptor (ER) expression in EC patients, we examined this pathway in 199 EC patients with data from the University of Pittsburgh Medical Center Cancer Registry. Immunohistochemistry (IHC) was used to detect CXCR4, CXCL12 and ER protein expression. As CXCR4 expression was positive in all cases, this investigation focused on associations between CXCL12 and ER expression, clinicopathologic factors and survival outcomes using chi-square tests, Kaplan-Meier graphs, and log-rank tests. CXCL12 expression was negative in 63 cases (32%) and positive in 136 cases (68%). Negative CXCL12 expression was borderline significantly associated with metastasis (χ2 p = 0.07). ER expression was negative in 75 cases (38%) and positive in 124 cases (62%). Positive ER expression was significantly associated with low grade and early stage tumors (χ2 p < 0.001). CXCL12 and ER were not significantly associated (χ2 p = 0.11). Positive CXCL12 expression was associated with longer overall survival (OS) (log-rank p = 0.006) and longer recurrence-free survival (RFS) (log-rank p = 0.01) in ER negative patients, but not in ER positive patients. We identified a unique molecular signature associated with better OS and RFS in EC patients. In addition to pathological characteristics of the tumor, expression of CXCL12 and ER may be clinically useful for assigning adjuvant treatment to EC cases. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Optimal management of early-stage uterine papillary serous carcinoma (UPSC) remains controversial. We reviewed our outcomes in this patient population. Methods: The Roswell Park Cancer Institute (RPCI) tumor registry identified all patients with Stages I and IIA UPSC treated between January 1992 and June 2006. The Fisher''s exact test was used to compare recurrence rates by adjuvant therapy received. Overall survival (OS) estimates were made using the Kaplan–Meier method. Results: Fifty-eight patients with Stage I or IIA UPSC underwent surgery. Thirty-four patients (59%) were surgically staged. Among 21 patients with Stage IA disease, 15 received adjuvant therapy. With a median follow-up of 44.7 months, only one recurrence was observed in a patient who received adjuvant brachytherapy. The 5-year OS was 66%. Among 37 patients with Stages IB–IIA, 30 patients received adjuvant therapy. With a median follow-up of 29 months, there were 7 recurrences. The 5-year OS was 60%. Although there were no significant differences in recurrence by adjuvant therapy received, a significant OS benefit was found in those who received radiation. There was no significant difference in OS distributions of those patients who received Carboplatin/Paclitaxel chemotherapy. Conclusions: Despite the limitations of our retrospective study, we have shown that even comprehensively staged early-stage UPSC patients are still at risk for recurrence despite adjuvant therapy received. Hence, all patients with this histologic diagnosis should be considered at high risk for recurrence and counseled appropriately regarding the risks and benefits of adjuvant therapy. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the usefulness of pre-operative serum CA-125 in the management of women diagnosed with uterine papillary serous carcinoma (UPSC). We hypothesized that elevated pre-operative levels of serum CA-125 correlate with higher disease stage and poorer prognosis. Methods: Patients diagnosed with UPSC and managed in our institution were identified over a period of 10 years, 1995 to 2005. All required information were extracted from their records. The nonparametric test applied for comparison of data included Kruskal Wallis H-test and Man–Whitney U-test. The χ 2 test and Spearman correlation test were used to examine the association of serum CA-125 with different parameters. Receiver operator characteristic curves (ROC) were used to quantify marker performance. Recurrence and survival were analyzed using Kaplan–Meier method. Multivariate analyses were performed with a Cox proportional regression method. Results: A total of 41 patients met the study criteria. Mean pre-operative serum CA-125 levels were significantly higher in patients with stage IV (1150±1297 U/mL), compared with stage III (181±232 U/mL; P <0.001), stage II (22±9; P <0.001), and stage I (14±1; P <0.001). CA-125 correlated strongly with stage (r =0.68, P <0.001). On the ROC, a cut-off of 35 IU/mL provided the best sensitivity and specificity (78% vs. 100% respectively) for extra-uterine disease. Disease free survival (DFS) and overall survival (OS) were longer in patients with CA-125<35 U/mL compared with CA-125≥35 U/mL [median DFS not reached during study vs. 21.2 months (P =0.009), and median OS not reached during study vs. 25 months, (P =0.0001) respectively]. Multivariate regression model showed CA-125 as the only variable associated with survival (P =0.05). Conclusion: Pre-operative serum CA-125 levels correlate with stage of disease in patients with UPSC. This may be important for management planning, prognostication and counseling in these women. [Copyright &y& Elsevier]

Abstract: Objectives. : Oligonucleotide array and tissue microarray analysis (TMA) by our group has revealed that folate binding protein (FOLR1) is overexpressed in some types of uterine cancer, particularly tumors with serous histology. Since FOLR1 overexpression is a frequent event in some types of endometrial carcinoma, we examined the relationship between FOLR1 overexpression and clinical and pathologic features to determine its prognostic relevance. Methods. : A tissue microarray (TMA) comprised of primary tumor specimens from 485 patients diagnosed with endometrial adenocarcinoma was used to identify cases characterized by FOLR1 overexpression. A proportional hazards model was used to evaluate the association of FOLR1 overexpression with progression-free survival while accounting for confounding influences. Results. : Overexpression of FOLR1 was observed in 50/292 (17%) cases and was seen more often in poorly differentiated cancers (22/90 [24%], p =0.051) and tumors with serous histology (16/32 [50%], p <0.001). A shorter progression-free survival was noted in patients with FOLR1 overexpression (log-rank p =0.016) that persisted when the data were limited to patients with stage III/IV disease (log-rank p =0.021) or serous tumors (log-rank p =0.020). Multivariate Cox regression analysis revealed that patients with FOLR1 overexpression had a shorter progression-free survival (H.R. 2.14; 95% CI 1.07–4.28) even when controlling for stage, grade, myometrial invasion and adjuvant chemotherapy. Conclusions. : Our data show that FOLR1 overexpression is not only a biomarker associated with endometrial cancer, but it also appears to be a prognostic factor associated with adverse outcome. These findings suggest that FOLR1 may be an appealing target for biological therapies in some types of endometrial carcinomas. [Copyright &y& Elsevier]

Abstract: Purpose : Folate receptor alpha (FOLR1) is a membrane bound receptor involved in the transport of folate as well as other regulatory cellular processes. The purpose of this study was to examine the expression of FOLR1 in uterine cancers and to identify changes in gene expression that are associated with overexpression of FOLR1. Experimental design : Fifty-eight frozen uterine cancer specimens were stained for FOLR1 using immunohistochemistry and results were correlated with transcript expression noted on quantitative PCR. Total RNA from 16 cases of uterine serous carcinoma (USC) was analyzed for gene expression using the Affymetrix HG-U133A and HG-U133B GeneChip set. USCs overexpressing FOLR1 were compared to cancers with an absence of FOLR1 using binary comparison and template matching of data was used to identify genes that correlate with FOLR1 expression. Selected targets from this analysis were evaluated by quantitative PCR as well as in an independent set of USC represented in quadruplicate on a tissue microarray (TMA). Results : Overexpression of FOLR1 was observed in 11/16 (69%) of USC and 0/10 normal endometrium cases using frozen tissue specimens. Binary comparison between FOLR1 positive and negative cases identified 121 genes altered by 2-fold at p <0.01 of which 45 are well correlated with FOLR1 expression pattern. Using quantitative PCR, both mesothelin (MSLN) and PTGS1 (COX1) were significantly increased in FOLR1 overexpressing tumors (p =0.014 and p =0.006 respectively). TMA confirmed that overexpression of FOLR1 and MSLN respectively occurred in 23/48 (48%) and 17/54 (32%) of pure USC. Conclusion : Both FOLR1 and MSLN are cell surface targets that are co-expressed at high levels in USC and are appealing targets for biologic therapy. [Copyright &y& Elsevier]

Abstract: Objective. : To analyze corpus cancer patients with a breast cancer history for risk of developing aggressive uterine histologic types. Methods. : Corpus cancer patients with a history of breast cancer were identified from the Surveillance Epidemiology and End Results database from 1988 to 2001. Demographics, clinico-pathologic, and survival data were analyzed using Kaplan–Meier and logistic regression analyses. Results. : Of 52,109 women diagnosed with corpus cancer, 1922 had a history of breast cancer. Women with a history of breast cancer had a significantly higher proportion of uterine papillary serous carcinomas (UPSC) and sarcomas compared to those without a breast cancer history (9.4% vs. 6.3% for UPSC and 10.3% vs. 8.4% for sarcoma; P < 0.001). Patients with endometrioid or sarcoma of the uterus after breast cancer had significantly worse 5-year survivals than patients without a breast cancer history (84.4% vs. 90.5%; P < 0.001 and 49.0% vs. 63.6%, P < 0.001, respectively). Older age, advanced stage, lack of surgery and radiation treatment, poor histologic types, and history of breast cancer were independent prognostic factors for poorer survival. Conclusion. : In this study, the proportional incidence of UPSC and sarcoma was significantly higher in women with a breast cancer history. These findings highlight the association of breast cancer and high-risk corpus cancer subtypes. [Copyright &y& Elsevier]

Abstract: Objectives.: To evaluate outcome in patients with clinical stage I/II papillary serous (PS) or clear cell (CC) endometrial carcinoma treated with whole abdominal radiotherapy. Methods.: After total abdominal hysterectomy with bilateral salpingo-oophorectomy, pelvic/para-aortic lymph node sampling, and peritoneal washings, eligible patients received radiotherapy (RT) to the abdomen (3000 cGy at 150 cGy/day) with a pelvic boost (1980 cGy at 180 cGy/day). Results.: Among 21 PS patients (median age: 68 years), one refused therapy, and another received a non-protocol vaginal boost. In total, eight patients died of disease (DOD) between 9.6 and 35.2 months. Five others died due to protocol treatment (1), toxicity from subsequent chemotherapy (1), intercurrent disease (1), and unknown cause (2). Five-year progression-free survival (PFS) was 38%. Among treated patients who DOD, sites of recurrence included lung (2), lung/vagina (1), abdomen/pelvis (1), vagina (1), and abdomen (2). Among 13 CC patients (median age: 63 years), one received pelvic RT only and died with intercurrent disease. Five others died due to DOD (3), intercurrent disease (1), and unknown cause (1). Five-year PFS was 54%. Among patients who DOD, sites of recurrence included lung (1), vagina (1), and unknown (1). Grade 3/4 toxicities for both histologic groups included gastrointestinal (three grade 4; three grade 3), hematologic (one grade 4), and cutaneous (one grade 3). Conclusions.: Over half of the treatment failures were within the radiation field. Systemic chemotherapy, radiosensitizing chemotherapy, or sequential radiation and chemotherapy should be considered in future adjuvant trials for these patients. [Copyright &y& Elsevier]

Abstract: Objective. : To explore factors that determine the response of endometrial cancer to radiation therapy. Such factors may influence treatment outcome and yield predictive information about individual patients and their tumors. Methods. : A retrospective study of the complete pathologic response (pCR) rates in the hysterectomy specimens of patients, who had undergone pre-operative radiotherapy for ≥ Stage II biopsy-proven endometrial carcinoma, was performed. 62 patient records were reviewed with respect to patient characteristics, tumor stage, histological grade and subtype, radiation technique and dose, and presence or absence of pCR in the post-operative hysterectomy specimen. Results. : 24 of 62 specimens exhibited a pCR. The only significant factor with respect to pCR was presence of uterine papillary serous carcinoma (UPSC). None of the seven cases of UPSC displayed a pCR (P = 0.036 Fischer''s exact test), despite not differing from the non-UPSC cases in any other tumor, treatment, or patient factors. No factors were found that separated non-UPSC cases with a pCR from those without. Conclusions. : These data suggest an intrinsic radioresistance within UPSC, which may have implications for future treatment strategies. UPSC has documented genetic aberrations that may account for this, although its true radiosensitivity has yet to be quantitated directly. Future studies should focus on the molecular basis of its response to radiation. The reasons for the heterogeneous response of non-UPSC has yet to be elucidated and should also be investigated. [Copyright &y& Elsevier]

Objective. To determine the efficacy of high-dose rate brachytherapy as adjuvant treatment for Stage I/II papillary serous or clear cell endometrial cancer.Methods. A retrospective study of all patients with Stage I/II papillary serous or clear cell endometrial cancer treated with high-dose rate brachytherapy between 1995 and 2001 was performed. Following surgical staging, which included hysterectomy with pelvic and aortic lymphadenectomy, all patients without extrauterine disease were treated with high-dose rate brachytherapy and followed for recurrence. The locations of recurrences were noted and were classified as local or distant.Results. Three (13%) recurrences occurred among 24 patients with Stage I/II papillary serous or clear cell carcinoma. The risk of recurrence was similar for papillary serous and clear cell cancer (12% vs. 12%). Local control was achieved in 96%. The risk of recurrence for those with no myometrial invasion, less than 1/2, or more than 1/2 myometrial invasion was 0%, 10%, and 50%, respectively (P < 0.04). Two of the three recurrences were distant and all patients with recurrence died despite additional treatment.Conclusions. High-dose rate brachytherapy (HDR) as the sole adjuvant treatment of Stage I/II papillary serous or clear cell carcinoma is associated with a 13% risk of recurrence. Although local control with HDR is excellent, the risk of distant recurrence is increased with deep myometrial invasion. High-dose rate brachytherapy is adequate for Stage IA cases, but more aggressive treatment combining chemotherapy with HDR should be evaluated for more advanced Stage I/II cases. [Copyright &y& Elsevier]

: PurposeTo evaluate the outcome and patterns of failure in women with pathologic Stage I–II papillary serous carcinoma of the uterus and to discuss the implications for adjuvant radiation therapy (RT).: MethodsTwenty-three pathologic Stage I–II uterine papillary serous carcinoma patients were treated at our institution between 1980 and 2001. All underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy and assessment of peritoneal cytology. Pelvic and para-aortic lymph node sampling was performed in 12 and 8 patients, respectively. FIGO stages were as follows: IA = 3, IB = 8, IC = 6, IIA = 5, and IIB = 1. Adjuvant therapies included the following: 9 none, 10 RT (6 pelvic, 1 vaginal brachytherapy, 3 both), 4 chemotherapy, and 1 hormonal therapy. No patient received whole abdominal radiation therapy or para-aortic RT. Disease-free survival, pelvic recurrence–free survival, and cause-specific survival were estimated using the method of Kaplan-Meier, and prognostic factors were analyzed by the log–rank test. Median follow-up was 38.7 months (range: 3–109 months).: ResultsThe 5-year actuarial disease-free survival and cause-specific survival for the entire group was 41% and 73.6%, respectively. Nine patients developed recurrent disease. Five failed in the pelvis, of which 4 relapsed in the vagina. No pelvic failures occurred in women treated with adjuvant RT. Patients treated with adjuvant RT had a better 5-year actuarial pelvic recurrence–free survival (100% vs. 57.5%, p = 0.06) than patients treated with surgery alone. Two patients failed in the abdomen. However, neither developed an isolated abdominal recurrence. Six patients failed in distant sites, primarily the lungs and bone.: ConclusionAlthough patients with pathologic Stage I–II uterine papillary serous carcinomas have organ-confined disease, recurrence is common, particularly in the pelvis and distant sites. Our results suggest that adjuvant RT reduces the risk of pelvic failure. Contrary to traditional assumptions, however, abdominal recurrence was uncommon in our patients, despite the lack of whole abdominal radiation therapy. Our results support the use of pelvic RT in these patients. Future studies should investigate the role of adjuvant chemotherapy. [Copyright &y& Elsevier]

Purpose: Several reports in the literature have shown that, compared with endometrioid adenocarcinoma, patients with papillary serous (PS) and clear cell (CC) histologic features do worse. However, it is unclear whether the outcome of PS/CC cancer is different from that of poorly differentiated endometrioid cancer. The purpose of this study was to compare the outcome between PS/CC and endometrioid International Federation of Gynecology and Obstetrics (FIGO) Grade 3 cancer and was limited to patients with Stage I–II uterine carcinoma.Methods and Materials: Between November 1987 and September 1999, 83 patients with Stage I endometrial cancer and Stage II occult endometrial cancer were treated with simple hysterectomy and high-dose-rate intravaginal brachytherapy. Forty-one patients (49%) had FIGO Grade 3 endometrioid tumors (Group 1) and 42 (51%) had PS/CC histologic features (Group 2). The mean age was 63 years (range 30–89). Comprehensive surgical staging was done in 23 (28%) of 83 patients. Capillary space-like invasion (CSLI) was seen in 24 (29%) of 83 patients. The median dose of intravaginal brachytherapy when used alone was 21 Gy in 3 fractions. Additional external beam radiotherapy was given to 42 (51%) of 83 patients to 45 Gy. The two groups were balanced with regard to age, race, comprehensive surgical staging, amount of myometrial involvement, CSLI, lower uterine segment involvement, cervical involvement, and use of external beam radiotherapy. The median follow-up was 46 months (range 4–147).Results: The pattern of relapse was as follows: vagina/pelvis in 5 of 14 patients, lungs in 8 of 15, intra-abdominal in 4 of 12, and supraclavicular lymph nodes in 1 of 14. One of the four intra-abdominal disseminations was in Group 1 and the other three in Group 2 (p = 0.6). The 5-year vaginal/pelvic control, disease-free survival (DFS), and overall survival (OS) rate was 93% (95% confidence interval [CI] 87–99%), 79% (95% CI 69–89%), and 74% (95% CI 64–85%), respectively. No significant difference in outcome was found between Groups 1 and 2. The 5-year vaginal/pelvic control rate was 97% (95% CI 91–100%) in Group 1 compared with 90% (95% CI 81–99%) in Group 2 (p = 0.2). The 5-year DFS rate was 79% (95% CI 64–95%) in Group 1 vs. 78% (95% CI 65–92%) in Group 2 (p = 0.6), and the 5-year OS rate was 71% (95% CI 55–87%) in Group 1 vs. 79% (95% CI 66–92%) in Group 2 (p = 0.3). The influence on outcome of age, race, comprehensive surgical staging, CSLI, amount of myometrial invasion, cervical involvement, lower uterine segment involvement, and presence of pure PS or CC histologic features was evaluated. On multivariate analysis, only CSLI correlated with poor DFS (p = 0.04; relative risk 3, 95% CI 1–9) and OS (p = 0.02; relative risk 3, 95% CI 1–6).Conclusion: On the basis of the results of this study, no significant difference in outcome exists between patients with Stage I–II endometrial cancer with PS/CC histologic features and those with similar stage disease, but with FIGO Grade 3 endometrioid histologic features. CSLI was the only independent predictor of poor DFS and OS. [Copyright &y& Elsevier]

Primary papillary serous carcinoma of peritoneum (PPSCP) is a rare type of primary peritoneal adenocarcinoma and is clinico-histopathologically indistinguishable from primary ovarian papillary serous carcinoma. A 70 -year- female presented with pain abdomen of 4 months duration. On examination partially mobile vague mass was present in the suprapubic region. Exploratory laparotomy revealed normal right ovary and the left ovary showed simple cyst. Nodular, firm tumour was seen arising from omentum and measured 20x13x9.3 cm. Microscopically tumour was composed of large sheets of polygonal cells having large hyperchromatic and pleomorphic nuclei and moderate amount of eosinophilic cytoplasm forming cribriform pattern and papillae. It has similar prognosis as that of ovarian malignancy. This case of extraovarian papillary serous carcinoma of peritoneum (EPSCP) is presented here for its rarity. [ABSTRACT FROM AUTHOR]