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e17022 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of cervical cancer (CC) patients assayed in a nationwide cancer network. Methods: 118 Pts with advanced CC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 47 years (range, 27-71), 69% were Caucasian. GA were identified in 88% (104/118) of CC, of which 87 (74%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most commonpresent in 73.5% (64/87) of CC. CRGA in other targetable pathways were identified: 24.1% (21/87) in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2), 9.1% (8/87) in HRD (BRCA1/2, ATM, PALB2, BRIP1) and 24.1% (21/87) in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). One patient was MSI-high and one patient was TMB-high. 29.8% (26/87) of CC patients were ordered a genomically-matched treatment, and 24 pts received treatment; 61.5% (16/26) were agents that were FDA approved in a different tumor type, and 34.6% (9/26) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The PFS for non study related patients was 7 weeks and OS was 19 weeks. Conclusions: In a large series of Cervical Cancer patients assayed with CGP, 27.5% (24/87) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

e17067 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of OC assayed in a nationwide cancer network. Methods: 449 Pts with advanced OC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant (CR) GA were defined as associated with targeted therapies or mechanism-driven clinical trials. Treatment histories for the 449 patients were obtained with IRB-approved retrospective review. Results: Median age was 56 years (range, 23-83), 71% were Caucasian. GA were identified in 94% (420/449) of OC, of which 283 (63%) had a clinically relevant genomic alteration (CRGA). 24.0% in HRD ( BRCA1/2, ATM, PALB2, BRIP1). CRGA in other potentially targetable pathways were identified: 48.0% MEK pathway ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) CRGA, 33.5% PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7), and 10.6% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). All OC tested were microsatellite stable and only one patient had a tumor mutational burden > 20 muts/Mb. 21% (59/283) of OC patients were ordered a genomically-matched treatment, 58% (37/64) were agents that were FDA approved in a different tumor type, and 17% (11/64) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. For the off label non-study population the median PFS was 19 weeks, and the median OS was 34 weeks. Conclusions: In a large series of OC assayed with CGP, 21% of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

e17123 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of endometrial cancer (EC) patients assayed in a nationwide cancer network. Methods: 278 Pts with advanced EC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 59 years (range, 37-85), 58% were Caucasian. GA were identified in 97% (271/278) of EC, of which 218 (80%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most common, present in 63.8% of EC. CRGA in other targetable pathways were identified: 28.4% in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) , 12.5% in HRD (BRCA1/2, ATM, PALB2, BRIP1 ) and 9.9% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). 26 patients are MSI-high 9.5% (26/271) and 21 patients are TMB-high 7.7% (21/271). 29.8% (65/218) of EC patients were ordered a genomically-matched treatment, and 61 of these patients received the treatment. 69.2% (45/65) were agents that were FDA approved in a different tumor type, and 24.6% (16/65) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The median PFS for non-clinical trial study patients was 9 weeks, and the median OS was 27 weeks. Conclusions: In a large series of Endometrial and Uterine cancer patients assayed with CGP, 27.9% (61/218) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.

Natalie Klag, Adam C Walter, Kristen M Sheely, Kelly J Manahan, John P Geisler Division of Gynecologic Oncology, Cancer Treatment Centers of America Newnan, Georgia, USA Background: New chemotherapy combinations are being tested for the treatment of women with advanced, persistent or recurrent cervical cancer. We sought to evaluate the cost effectiveness of some newer combination therapies in cervical cancer. Patients and methods: A cost effectiveness decision model was used to analyze Gynecologic Oncology Group 240. All regimens were modeled for seven cycles. The regimens studied are as follows: regimen 1, cisplatin/paclitaxel (CP); regimen 2, CP with bevacizumab (CP+B); regimen 3, paclitaxel/topotecan (PT); and regimen 4, PT with bevacizumab (PT+B). Overall survival, cost, and complications were studied. Sensitivity analyses were performed. Results: Mean chemotherapy costs over mean total costs for seven cycles of each follows: CP $571/$32,966; CP+B $61,671/$96,842; PT $9,211/$71,620; and PT+B $70,312/$109,211. Incremental cost-effectiveness ratio (ICER) for CP+B was $133,559/quality adjusted life year (QALY). ICER for PT+B was $124,576/QALY. To achieve an incremental ICER for CP+B:CP of 10 years for PT and 4.1 years for PT+B. Treating 1,000 women with cervical cancer with CP+B would cost almost double the cost of treating >18,000 women with ovarian cancer annually (carboplatin/paclitaxel). Conclusion: CP is the most cost effective regimen. A 12-month increase in overall survival will not even make the newer combinations cost effective. Currently, the use of bevacizumab is not sustainable at today's costs. Keywords: cervical cancer, chemotherapy, bevacizumab, cost-effectiveness

Ovarian malignant mixed Mullerian tumors (MMMTs) are uncommon cancers. The purpose of the study was to determine the rate of metachronous or synchronous breast cancer as well as the rate of truncating germline BRCA1 and/or BRCA2 mutations in a series of women with these uncommon tumors. Records were reviewed to identify all women with MMMTs treated by the gynecologic oncology service. The stage, grade, histology, survival, and rate of coexistent breast cancer were determined. Tumor and/or peripheral blood was tested for BRCA1 and BRCA2 truncating mutations. Twenty-four patients with MMMTs were found. Tumor and paired peripheral blood was available on 20 patients and 4 more patients had only peripheral blood available. Family pedigrees were available on all 24 patients. Fifteen of 24 (62.5%) patients were found to have metachronous or synchronous breast cancers with 9 of 15 (60%) having bilateral breast cancer. No BRCA1 or BRCA2 mutations were found (somatic or germline) in this cohort. Although an uncommon tumor, MMMTs are often found in women with breast cancer. Despite this finding, BRCA1 or BRCA2 germline mutations are not common in this population. Ovarian MMMTs are frequently found in women with cancer but are not frequently associated with defects in BRCA1 or BRCA2.

e15554Background: Resin Yttrium-90 hepatic arterial liver directed treatments are commonly used in the treatment of liver predominant metastatic colorectal carcinoma. Although its role in first lin...

e18939Background: Medications in the U.S. are approved by the FDA based upon safety and efficacy data, not price. The object of this study was to model (or forecast) potential prices for bevacizuma...

Background: Breast cancer is one of the most common cancers in women. Many patients are treated with tamoxifen therapy after diagnosis for 5 years. Cases: In this article, we present 3 patients who developed uterine adenosarcoma with rhabdomyosarcoma overgrowth following a history of breast cancer treated with tamoxifen for at least 5 years. All patients had completely staged stage IA adenosarcoma. All 3 tumors had the same distinct immunohistochemical staining pattern: vascular endothelial growth factor strongly positive, c-kit (CD117) weakly positive, nonspecific muscle actin strongly positive, smooth muscle actin negative, estrogen-receptor negative, and progesterone-receptor negative. Conclusions: This staining may be an identifying set of features for adenosarcomas with rhabomyosarcomatous overgrowth related to tamoxifen therapy. Uterine adenosarcoma with rhabdomyosarcoma overgrowth may be associated with previous tamoxifen treatment for breast cancer and has a very specific staining pattern...

Background The purpose of this study was to determine whether vascular endothelial growth factor (VEGF) expression in tumors correlates with the incidence of an elevated prothrombin time (PT), specifically an international normalized ratio (INR) ≥ 1.4, in patients undergoing primary surgical cytoreduction for ovarian cancer. Methods INRs were obtained on all patients perioperatively. VEGF expression was determined by immunostaining of tumor specimens using published protocols. Results One hundred patients underwent surgical cytoreduction. Sixty-seven percent of patients had postoperative INR of 1.4 or greater. INRs of greater than or equal to 1.8 were found in 5% of patients. INR elevation was independent of mean estimated blood loss (EBL) with the EBL in the patients with INRs ≥ 1.4 not significantly different than the EBL in the patients with INRs

It has been postulated that androgens, through their interaction with androgen receptors (AR), may play an important role in the development of ovarian cancer. Exon 1 of the AR gene contains three highly polymorphic trinucleotide repeats. The length of the (CAG)n repeat segment 1 is inversely correlated with the transactivation function of the AR. Recent studies have shown that BRCA1 may function as an AR coregulator or coactivator and play positive roles in androgen-induced cell death in cancer cells as well as other androgen/AR target organs. We hypothesize that the AR gene, involved in endocrine signaling, may modify BRCA1-associated ovarian cancer risk. To test this hypothesis, potential associations between the (CAG)n repeat length, germ line BRCA1 mutation status, and age of diagnosis for ovarian cancer were investigated. One hundred and eleven ovarian cancer patients (27 hereditary and 84 sporadic) were included. All the cases were allelotyped for CAG repeat length and genotyped for mutations in the BRCA1 gene by direct sequencing. No association between CAG repeat length and BRCA1 mutation status was identified. Furthermore, there were no differences between hereditary and sporadic ovarian cancer in the number of (CAG)n repeats of the short allele (P= 0.336), long allele (P= 0.875), or average allele length (P= 0.550). However, ovarian cancer patients from both groups (hereditary and sporadic) who carried any AR allele of (CAG)nor = 22 repeats were diagnosed on average 8.17 years (95% confidence interval [1.3, 15.0]) earlier than the patients whose shortest AR allele (CAG)n was22 (P= 0.020). In conclusion, it is suggested that the CAG repeat length in AR exon 1 may affect the age of diagnosis of ovarian cancer but does so independent of germ line BRCA1 carrier status.

Purpose: The purpose is to investigate the safety and efficacy of i.p. topotecan and oral etoposide as salvage treatment for patients with platinum-resistant ovarian or primary peritoneal cancer. Experimental Design: Patients were treated with i.p. topotecan initial dose, 1 mg/m2 on days 1 to 5, followed by oral etoposide 100 mg on days 6 to 9 of a 28-day cycle for six cycles. Dose reduction of topotecan was used for severe bone marrow suppression. Peritoneal (topotecan) and plasma (topotecan and etoposide) levels were assessed at multiple time points using high-pressure liquid chromatography. Results: Twenty-two patients (mean age, 61 years) with a median of 1.5 prior treatments were enrolled. Etoposide peak plasma concentrations ranged from 1.9 to 6.9 μg/mL (mean, 3.6 μg/mL). Topotecan plasma levels rose with increasing peritoneal concentration and were detectable within 1 hour but tended to decrease rapidly to below detectable levels within 24 hours. The peak plasma concentration of topotecan was 12.82 ± 8.55 μg/mL with a plasma half-life of 6.17 ± 2.75 hours. A total of 104 cycles was administered; 14 patients (64%) completed all six planned cycles. All patients were evaluable for toxicity, and 21 patients were evaluable for response. The most common grade 4 toxicities were neutropenia and thrombocytopenia in eight and four patients (36 and 18%), respectively. There were no treatment-related deaths. The overall response rate was 38% [complete response, three (14%); partial response, five (24%)]. Seven patients had stable disease and six progressed while on treatment. Conclusions: The combination of i.p. topotecan and oral etoposide is an active and well-tolerated regimen in platinum-resistant ovarian carcinoma. Additional studies investigating topotecan in combination with etoposide are warranted.

Currently available serum biomarkers are insufficiently reliable to distinguish patients with epithelial ovarian cancer (EOC) from healthy individuals. Metabonomics, the study of metabolic processes in biologic systems, is based on the use of (1)H-NMR spectroscopy and multivariate statistics for biochemical data generation and interpretation and may provide a characteristic fingerprint in disease. In an effort to examine the utility of the metabonomic approach for discriminating sera from women with EOC from healthy controls, we performed (1)H-NMR spectroscopic analysis on preoperative serum specimens obtained from 38 patients with EOC, 12 patients with benign ovarian cysts and 53 healthy women. After data reduction, we applied both unsupervised Principal Component Analysis (PCA) and supervised Soft Independent Modeling of Class Analogy (SIMCA) for pattern recognition. The sensitivity and specificity tradeoffs were summarized for each variable using the area under the receiver-operating characteristic (ROC) curve. In addition, we analyzed the regions of NMR spectra that most strongly influence separation of sera of EOC patients from healthy controls. PCA analysis allowed correct separation of all serum specimens from 38 patients with EOC (100%) from all of the 21 premenopausal normal samples (100%) and from all the sera from patients with benign ovarian disease (100%). In addition, it was possible to correctly separate 37 of 38 (97.4%) cancer specimens from 31 of 32 (97%) postmenopausal control sera. SIMCA analysis using the Cooman's plot demonstrated that sera classes from patients with EOC, benign ovarian cysts and the postmenopausal healthy controls did not share multivariate space, providing validation for the class separation. ROC analysis indicated that the sera from patients with and without disease could be identified with 100% sensitivity and specificity at the (1)H-NMR regions 2.77 parts per million (ppm) and 2.04 ppm from the origin (AUC of ROC curve = 1.0). In addition, the regression coefficients most influential for the EOC samples compared to postmenopausal controls lie around delta3.7 ppm (due mainly to sugar hydrogens). Other loadings most influential for the EOC samples lie around delta2.25 ppm and delta1.18 ppm. These findings indicate that (1)H-NMR metabonomic analysis of serum achieves complete separation of EOC patients from healthy controls. The metabonomic approach deserves further evaluation as a potential novel strategy for the early detection of epithelial ovarian cancer.

ObjectiveThe authors, using image analysis, previously demonstrated nuclear size and summed optical density to be independent prognostic indicators of recurrence in patients with endometrial carcinoma. The same tumors were analyzed by studying the optical features in the G0–G1 peak to see if this changed the values found as well as their importance as prognostic features at greater than 5 years of follow-up.MethodsTumors from 74 consecutive patients, surgically treated, with endometrial cancer, were evaluated. Survival, depth of invasion, lymphvascular space invasion, FIGO stage, grade, histology were analyzed. DNA index, progesterone receptor status, as well as nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD) were evaluated. NUSZ, NUSH, and NUSD were quantified using image analysis.ResultsFifteen patients died from disease during the observation period of the study. Mean follow-up was 82 months with a median of 84 months. Forty-nine patients had stage I cancers, five stage II, 17 stage III, and three stage IV. NUSZ and NUSD were all significantly different between the original (entire cell cycle) and the re-measured (G0G1 only) values (both P < 0.001). Multivariate analysis showed both the original (P = 0.0001) and G0G1-only (P = 0.046) NUSZ and the original (P = 0.0002) and G0G1-only (P = 0.018) NUSD to be independent prognosticators of survival.ConclusionImage analysis is able to quantify cellular and nuclear parameters not otherwise quantifiable. NUSD and NUSZ correlated with traditional prognostic indicators, were demonstrated independent predictors of survival at over 5 years of follow-up. Although the re-measured NUSZ and NUSD from only the G0–G1 peak were significantly different from the original NUSZ and NUSD, they were not as valuable as prognostic factors. Nuclear size and summed optical density measured from the entire cell cycle are independent prognostic indicators of survival at greater than 5 years of follow-up. Measuring nuclear morphometric features in the G0–G1 peak only does not add any new prognostic information.

ObjectiveThe role of the c-myc proto-oncogene in genomic instability is just becoming more fully understood. However, its role in endometrial cancer is essentially unknown. The objective of this study was to determine the relationship between cytoplasmic and nuclear c-myc staining, DNA index, and survival in patients with endometrial carcinoma.MethodsOne hundred and twenty-one patients with endometrial carcinoma were studied. Image analysis was used to determine DNA index. In addition to cytoplasmic and nuclear c-myc staining and DNA index, histologic type, stage, grade, depth of invasion, lymphvascular space invasion, and peritoneal cytology were evaluated as prognostic indicators. Univariate and multivariate analyses were performed.ResultsOne hundred and twenty-one patients were followed for over 5 years. c-myc cytoplasmic staining was present in 75.2% of the patients' tumors, and nuclear staining was present in 66.9% (P = 0.99). DNA index was significantly higher in patients with nuclear c-myc staining and no cytoplasmic staining (DNA index 1.38) as compared to those patients whose tumors displayed cytoplasmic c-myc staining but no nuclear c-myc staining (1.18) (P = 0.016). Patients whose tumors stained positively for nuclear c-myc and negatively for cytoplasmic c-myc had significantly worse survival by Kaplan–Meier analysis (P < 0.0001). Seventeen patients died during the follow-up period of this study. By multivariate analysis, positive cytoplasmic c-myc staining with negative nuclear staining (P = 0.0076), negative cytoplasmic c-myc staining with positive nuclear staining (P = 0.011) and FIGO stage (P < 0.0001) were shown to be independent prognostic indicators predictive of survival.ConclusionNuclear and cytoplasmic c-myc staining, as well as FIGO stage, when assessed by multivariate analysis, were demonstrated to be important factors in predicting survival in the 121 patients in this study. While increasing FIGO stage was prognostic of decreased survival, the specific location of c-myc staining was also associated with prognosis. The expression of the c-myc protein is related to survival in patients with adenocarcinoma of the endometrium.

e17042 Background: At initial presentation, patients with ovarian cancer often have disease involving the upper abdomen and specifically the liver (surface or parenchyma). The object of this study was to 1) see the difference in liver enzyme levels in women getting tumor ablation involving the liver compared to women getting tumor ablation not involving the liver and to 2) see if any differences had a readily noticeable clinical effect. Methods: A series of twenty women with initial diagnosis of ovarian cancer undergoing primary cytoreduction with tumor ablation involving the liver were compared to twenty women with initial diagnosis of ovarian cancer undergoing primary cytoreduction and tumor ablation without involvement of the liver. The data were compared with Fisher’s exact, Chi-square or Mann-Whitney U as appropriate. Results: Women undergoing tumor ablation involving the liver compared with women undergoing tumor ablation not involving the liver had significantly elevated AST and ALT levels the first day after surgery (p = 0.002; 0.002, respectively). There were no significant differences in age, operative blood loss or need for transfusion (p=0.24; 0.065; 0.33, respectively). The mean time for resolution of the elevations of AST and ALT was 2.5 days (95% CI = 1.8-3.2) for AST and 2.8 days (95% CI = 2.0 -3.6) for ALT. Conclusions:Significant elevations in AST and ALT occur when tumor involving the liver is ablated in women undergoing debulking for ovarian cancer. This elevation does not appear to increase operative blood loss or need for transfusion.

OBJECTIVE The objective was to determine how often peritoneal cytology is positive for malignancy in women with known ovarian cancer. Knowing this fact would help determine the usefulness of diagnostic paracentesis. METHODS Records of all women diagnosed with invasive epithelial ovarian cancer from 2004 to 2012 were examined to correlate presence of ascites, cytologic, and pathologic findings. RESULTS A total of 313 patients were included in analysis. A total of 210 of 313 patients (67.1%) with ascites had cytology positive for malignancy. This left 103 patients with ascites and cancer without malignant cells found in the ascites removed at the time of surgery. CONCLUSIONS Except in a few cases, paracentesis is not recommended for the diagnosis of ovarian cancer because of the potential spreading of cancer. Furthermore, with only just over two thirds of cases of known cancer and ascites having cytology positive for malignancy, the value of paracentesis for diagnosis of ovarian cancer is minimal.

Gynecologic oncology is a rapidly growing field due to constant advances in immunohistochemistry and molecular biology. This review serves as an overview of new studies promoting the use of tumor markers and molecular biological prognostic factors in malignancies affecting women. The majority of studies focus on either endometrial or ovarian carcinoma. Other gynecologic malignancies (cervical, vulvar, and vaginal carcinoma) have a much smaller representation in the world literature. Multiple new markers were examined over the last year. We conclude that although some markers show promise as potential new consensus prognostic indicators, more work is needed to confirm results and clarify any existing discrepancies.

BACKGROUND Mutations in p53 are the most common genetic alterations in human malignancies. Expression of its protein product has been linked to decreased survival rate in ovarian carcinoma. Less is known about the importance of p21 expression. The purpose of this study was to determine the value of the combination of p21 and p53 expression in patients with epithelial ovarian malignancies. METHODS One hundred three consecutive patients with epithelial ovarian carcinoma were studied using snap-frozen tissue specimens. Immunohistochemical staining utilizing the pAb1801 monoclonal antibody to p53 and NCL-WAF-1 monoclonal antibody to p21 was performed. Image analysis was used to determine whether nuclear staining for either antibody was present. In addition to p21 and p53, International Federation of Gynecology and Obstetrics stage, grade, histology, level of cytoreduction, and DNA index were analyzed as prognostic factors. Univariate and multivariate analyses was performed. RESULTS One hundred three patients were observed for more than 5 years. Immunohistochemical staining for p21 and p53 were significantly inversely related (P = 0.041). Among the patients whose tumors showed p21 staining but no p53 staining, there were no recurrences and all patients were alive at 5-year follow-up. The 5-year survival rate for these patients was significantly better than for the patients with other combinations of p21/p53 staining (P < 0.0001). The DNA index between these 2 groups was not significantly different (P = 0.057). Multivariate analysis shows the combination of p21 and p53 (P = 0.013) staining to be more valuable as a prognostic indicator than either p53 (P = 0.015) or p21 (P = 0.5) alone. CONCLUSIONS This study confirms the importance of the combination of p21 and p53 nuclear staining in patients with ovarian carcinoma. Cox regression analysis revealed combination of p21 positive and p53 negative to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than either p21 or p53 alone. Cancer 2001;92:781–6. © 2001 American Cancer Society.

Objective. MIB-1, a monoclonal antibody to the Ki-67 antigen, has presumptively been shown to be predictive of recurrent disease in patients with endometrial cancer. In order to more conclusively establish whether MIB-1 staining can be used as a prognostic indicator of recurrent disease or survival, a larger group of patients with a minimum follow-up of 5 years was analyzed. Methods. The tumors from 147 consecutive patients receiving primary surgical therapy for endometrial carcinoma were evaluated with the MIB-1 monoclonal antibody. Proliferation index was quantified by image analysis. Patients were followed for a minimum of 60 months. In addition to MIB-1 staining, histologic type, stage, grade, depth of invasion, lymphovascular space invasion, and peritoneal cytology were evaluated as prognostic indicators. Results. Twenty-five of 147 patients died during the study period. MIB-1 staining was not significantly elevated in advanced (stage II, III, and IV) as opposed to early (stage I) carcinomas ( P = 0.38). In patients whose tumor MIB-1 staining was less than 33.0%, no deaths occurred. By multivariate analysis, only MIB-1 staining ( P P = 0.005), and LVI ( P = 0.005) were shown to be independent prognostic indicators predictive of survival. Conclusion. In this series of 147 consecutive patients with endometrial carcinoma, the monoclonal antibody MIB-1 was shown to be an independent prognostic indicator of 5-year survival. This follow-up further validates the previous work regarding the significance and potential usefulness of MIB-1 as a prognostic indicator.

One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. The purpose of this article was to build upon the authors' previous work with p53 and determine whether p53 was a prognostic indicator of 5-year survival.One hundred thirty-seven consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis. All patients were evaluable for 5-year survival.One hundred three patients had endometrioid adenocarcinoma; 6, adenosquamous carcinoma; 14, papillary serous carcinoma; 10, clear cell carcinoma; and 4, undifferentiated carcinoma. p53 expression ranged from 0.0 to 58.2% positive nuclear area with a mean of 11.5% (median 2.6%) for the cohort. For the patients with endometrioid carcinoma, the mean p53 expression was 7.1% while for the nonendometrioid tumors it was 24.6% (P0.001). Fifty-nine of the 103 endometrioid tumors (57.3%) stained positive for p53 while 32 of the 34 nonendometrioid (94.1%) tumors stained positive (P0.001). Increasing histologic grade correlated with an increasing p53 expression (P = 0.003). The percentage of tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.003). However, mean p53 expression did not differ between early (stage I) and advanced (stage II, III, and IV) cancers (P = 0.088). Utilizing 5-year survival as the endpoint for multivariate analysis, FIGO stage (P = 0.0028) and p53 expression (P0.001) were the only independent prognostic indicators found.p53 expression is more commonly found in nonendometrioid than in endometrioid adenocarcinoma of the endometrium. It, along with FIGO stage, is an independent prognostic indicator of 5-year survival.

The perceived function of wild-type p53 is suppression of cell proliferation. An alteration in the p53 tumor suppressor gene is a common defect in human malignancies. The purpose of this study was to prospectively determine whether p53 expression, as quantified by image analysis, was related to traditional prognostic indicators as well as survival in patients epithelial ovarian cancer.Eighty-three consecutive patients with epithelial ovarian cancer had their p53 expression studied by immunohistochemical staining and quantified by image analysis. Unless otherwise noted, p53 expression was reported as the percentage positive nuclear area staining.The mean follow-up was 37 months (median, 30 months; range 24-55 months). In patients with serous carcinomas of the ovary, the mean p53 expression was 29.4%, whereas in patients with other histologies, the mean was 10.5% (P0.001). The tumors of patients with stage III or IV tumors stained significantly higher (mean 28. 7%) than the tumors of patients with stage I or II disease (mean 8. 36%) (P0.001). The tumors of patients with disease which could be optimally cytoreduced stained significantly lower (mean 23.0%) than the tumors of patients whose disease was unable to be optimally cytoreduced (mean 28.6%) (P = 0.041). Utilizing survival as the endpoint for multivariate analysis, FIGO stage (P = 0.006), p53 expression (P = 0.046), and the level of cytoreduction (P0.001) were independent prognostic indicators.Image analysis allows quantitative measurements of p53 staining. p53 staining is significantly higher in advanced-stage, high-grade tumors which are unable to be cytoreduced than in early-stage, low-grade tumors which can be optimally cytoreduced. p53 expression is an independent prognostic indicator of survival in patients with epithelial ovarian carcinomas.

Endometrial carcinoma is the most common gynecologic malignancy in developed countries affecting an estimated 140 000 women worldwide. Image analysis involves the integration of an optical microscope with a computer to describe cellular and nuclear features which may not otherwise be quantifiable. The authors, using image analysis, prospectively investigated three optical nuclear parameters to determine their relevance as prognostic indicators in endometrial cancer. Seventy-four consecutive patients with endometrial cancer, and who were being surgically treated, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, FIGO stage, grade, histology, as well as nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD). DNA index, nuclear size, shape and density were quantified using image analysis. Fifteen patients had a recurrence of disease and 12 patients died from disease during the observation period of the study. Median follow-up was 31 months with a range from 1–44 months. Fifty patients had stage I cancers, five had stage II, 16 had stage III, and three had stage IV. Nuclear summed optical density correlated well with traditional prognostic indicators: depth of myometrial invasion (P = 0.003), histologic grade (P = 0.01), DNA index (P

Extramammary Paget's disease of the lower female genito-urinary system is an uncommon neoplasm with a high rate of recurrence. A 52-year-old white female with a history of extramammary Paget's disease, originally excised in 1985 by skinning vulvectomy and who had multiple recurrences, including two in a vaginal graft and with extension to the urethra and the uterine cervix, in 1992 underwent an anterior pelvic exenteration for control of the disease process. Standard surgical management for extramammary Paget's disease without invasion or without an underlying adenocarcinoma is simple or skinning vulvectomy. However, because the disease commonly recurs, diffuse involvement may require more extensive surgery including pelvic exenteration in extraordinary cases.

Background Endometrial carcinoma is the most common gynecologic malignancy in developed countries, affecting an estimated 140,000 women. More than 32,000 women will be diagnosed with endometrial cancer this year in the United States, and approximately 6,000 will die from this disease. Methods Twenty consecutive patients, surgically treated, with advanced endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, as well as FIGO stage, grade, and histology. DI was determined using image analysis. Results Ten of the 20 patients had recurrence of their disease within the 3-year observation period of the study. A DI of ≥ 1.2 strongly predicted recurrence of disease (P = 0.002). Increasing histologic grade and an increasing DI were related (P = 0.01). Conclusion Independent of other prognostic indicators, including lymphovascular space invasion, depth of invasion, and histologic type, a tumor with a DI of ≥ 1.2, had a significantly increased chance of recurring within the 3-year observation period. © 1996 Wiley-Liss, Inc.

Background: Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Stage, grade, DNA index, histologic type, depth of invasion, steroid receptor status, and the presence of positive peritoneal cytology have all been linked to survival. The monoclonal antibody MIB-1 reacts with the same antigen as Ki-67 giving an estimate of proliferation index. The authors investigated whether MIB-1 staining, using image analysis, could be used as a prognostic indicator of recurrence in endometrial carcinoma. Methods: The tumors from 39 consecutive patients receiving primary surgical therapy for endometrial cancer were evaluated with the MIB-1 monoclonal antibody. Proliferation index was quantified by image analysis. The patients were followed for a median of 34 months and their charts were reviewed to determine recurrence, histologic type, grade, stage, depth of invasion, and status of peritoneal cytology. Results: Eleven of the 39 patients had recurrence of their disease within the 3-year observation period of this study. Overall, 22 patients had stage I disease, 3 patients had stage II disease, 12 patients had stage III disease, and 2 patients had stage IV disease. MIB-1 staining was not significantly elevated in advanced (stage III and IV) as opposed to early (stage I and II) cancers ( P = 0.558). Elevated MIB-1 staining was associated with an increased incidence of recurrence within 24 months of diagnosis ( P = 0.002). Patients whose tumors had MIB-1 staining of greater than or equal to 39.0% had an increased chance of recurring over patients whose tumors stained less than 39.0% ( P = 0.003). Conclusion: In this series of 39 patients with endometrial cancers, MIB-1 monoclonal antibody staining was shown to be a prognostic indicator of recurrence.

One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. Although endometrial cancer is the most common gynecologic malignancy in the United States, any connection between it and p53 is just beginning to be explored.Forty-six consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis.Thirty-five patients had endometrioid adenocarcinomas, 3 had adenosquamous carcinomas, 3 had papillary serous carcinomas, 3 had clear cell carcinomas, and 2 had undifferentiated carcinomas. p53 expression ranged from 0.0 to 55.8% with a mean of 10.7% for the cohort. For the patients with endometrioid carcinomas, the mean p53 expression was 3.9%, while for those with more aggressive histologies it was 32.4% (P0.001). Sixteen of the 35 endometrioid tumors (45.7%) stained positive for p53, while 11 of the remaining 12 (91.2%) tumors with more aggressive histologies stained positive (P0.01). Increasing histologic grade correlated with an increasing p53 expression (P = 0.006). The percentage of patient tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.01). However, the mean p53 expression was not different between early (stage 1) and advanced (stage 11, III, and IV) cancers (P = 0.55). Utilizing recurrence as the endpoint for multivariate analysis, FIGO stage and p53 expression were the only independent prognostic indicators found.p53 expression is more common in more aggressive histologic subtypes than in endometrioid adenocarcinomas. It is an independent prognostic indicator of disease recurrence.

Since the percentage of elderly patients in the United States is increasing, the knowledge of whether radical surgery can be performed on these patients with acceptable morbidity and mortality is important. Therefore, a retrospective study of elderly patients having radical hysterectomy was performed. A retrospective case study of all patients over 65 years of age having undergone a radical hysterectomy in one private community practice of gynecologic oncology was performed. No patients between July 1, 1965, and December 31, 1992, were knowingly excluded. All patients were analyzed for preexisting medical conditions, length of postoperative stay, morbidity, and mortality. Sixty-nine patients who fit the above criteria were found. Preexisting medical problems were found in 72.5% of the study population. Minor morbidity occurred in 14.5% of the group, while major morbidity occurred in 10%. There was no mortality. Lengths of hospital stay were significantly different between patients 65 to 74 (8.7 days) and over age 75 (10.4 days). In conclusion, radical hysterectomy is a safe surgical procedure in patients 65 and over. This is true even in patients 75 and over. Careful preoperative assessment, perioperative monitoring, and meticulous postoperative care is vital to the success of any major surgery, especially in the older patient.

Objective. Some women with endometrial cancer may be at increased risk for developing breast cancer. The histologic type of endometrial cancer associated with synchronous or subsequent breast cancer has not been clearly established. Our purpose was to determine if a certain histologic type of endometrial cancer was associated with an increased risk of synchronous or subsequent breast cancer. Methods. The University of Iowa Hospitals and Clinics tumor registry was queried to ascertain all patients with the diagnosis of uterine cancer from January 1, 1983, to December 31, 1994. Statistics were performed utilizing SPSS for Windows version 9.0 (SPSS Inc., Chicago, IL), including Student's t tests and χ 2 tests. Results. Five hundred ninety-two patients had endometrial adenocarcinoma during the study period. Five hundred thirty-six women had endometrioid adenocarcinoma, 23 women had papillary serous carcinoma (UPSC), 21 women had adenosquamous carcinoma, 10 women had clear-cell carcinoma, and 1 woman each had mucinous or squamous carcinoma. Twelve patients had previously been diagnosed with breast carcinomas. Twenty-five patients were diagnosed with breast cancer either concurrently or subsequent to their diagnosis of endometrial cancer. Synchronous or subsequent breast cancers developed in 3.2% of patients with endometrioid carcinoma and in 25% of patients with UPSC ( P Conclusion. Patients with UPSC have an increased risk of development of breast cancer as compared to patients with endometrioid adenocarcinoma of the uterus.

Radical hysterectomy is a common and effective treatment of early cervical cancer. Modern advances include the use of robotic assistance to perform equivalent minimally invasive procedures. The purpose was to compare surgical and short-term outcomes, as well as margins, between robotic-assisted laparoscopic radical hysterectomy and open radical hysterectomy.The first 30 cases of robotically assisted type III radical hysterectomy for cervical cancer were compared with the 30 previous cases of open type III radical hysterectomy. Body mass index, length of operation, nodal yield, margins, estimated blood loss, hospital stay, and complications were all documented and compared.The 30 patients undergoing robotically assisted laparoscopic radical hysterectomy were similar in body mass index to the women undergoing open radical hysterectomy (34 kg/m robotic, 32 kg/m open, P = 0.22). The mean operating time was 154 minutes compared with 166 minutes in the open arm (P = 0.36). The mean blood loss was 165 mL compared with 323 mL in the open arm (P = 0.001). The mean pelvic nodal yield was 25 nodes compared with 26 nodes in the open group (P = 0.45). The mean parametrial margin size was not significantly different between groups. The mean postoperative length of stay was 1.4 days compared with 2.8 days for the open cases (P0.001). Urinary retention was significantly more common in the robotic arm.Radical surgery for cervical cancer can be accomplished using the da Vinci surgical system (Intuitive Surgical, Sunnyvale, Calif) with acceptable blood loss, operating time, parametrial margins, and nodal yield. Future studies need to address long-term outcomes.

Highlights • Aprepitant combined with ifosfamide may lead to encephalopathy. • Aprepitant–ifosfamide induced encephalopathy was of short duration in these cases.

Objectives The objective of this pilot study was to determine if the combination of CA 125, menopausal status and prealbumin can be used to accurately predict ovarian cancer in women with pelvic masses. Study design Preoperative serum CA 125, prealbumin and menopausal status were prospectively determined. Results were formulated into an ovarian cancer risk assessment (OCRA) score and compared with final surgical pathology. Results OCRA was studied in 130 women. No cancers were found in women with a score less than 200. For all cancers, an OCRA score ≥ 200 had a sensitivity of 96%, specificity of 95% and positive predictive value of 95%. When the OCRA score of ≥200 was evaluated for its ability to predict ovarian cancer, the sensitivity, specificity, and positive predictive value were 100%, 83%, and 78%, respectively. Conclusions In this pilot study, OCRA was able to predict which women with pelvic masses were more likely to have ovarian cancer. The scoring system easily applied clinically and may help facilitate appropriate referral of women to gynecologic oncologists for optimal care.

Objective. While uterine papillary serous carcinoma (UPSC) is an aggressive histologic subtype, it fortunately is not as common as some other histologic subtypes. Overall, patients with UPSC have a poor survival rate. Since the optimal surgical procedure to perform on patients with this tumor is unknown, the authors wanted to determine what the optimal surgical management of patients with UPSC should be. Methods. All patients with the preoperative or frozen section intraoperative diagnosis of UPSC were treated with a staging or cytoreductive procedure analogous to patients with serous carcinoma of the ovary. Patients analyzed underwent surgery from March 1983 to September 1995. Results. Sixty-five patients with UPSC were found. Twenty patients had FIGO stage I tumors, 6 stage II tumors, 8 stage III tumors, and 31 stage IV tumors. Twenty-nine patients had upper abdominal disease (17 gross disease and 12 microscopic disease only). Forty-eight patients underwent pelvic and paraaortic lymphadenectomy, with 6 of 48 having positive lymph nodes. All 14 patients with lymphovascular space invasion had stage IV disease. Thirty-one of sixty-five patients had positive cytology at the time of surgery. Conclusion. Based on the clinical experience of these investigators, patients with UPSC should undergo a staging laparotomy similar to the procedure undertaken for patients with ovarian carcinoma. The surgery should include at least partial omentectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy, peritoneal washings, peritoneal biopsies, and pelvic and paraaortic lymphadenectomy similar to an ovarian cancer staging procedure if no gross disease ≥2 cm is found at time of surgery. If disease ≥2 cm is found, cytoreduction should be undertaken when feasible.

The purpose of this study was to determine if serum prealbumin could be used to objectively determine which patients could not safely undergo cytoreductive surgery.Patients with suspected ovarian cancer in a 24-month period underwent nutritional assessment during their preoperative workup and were followed for development of postoperative complications.One hundred and eight of 114 patients underwent surgical cytoreduction. Of the 108 surgical patients, 88 patients had prealbumin levels18 mg/dl and 24 patients had prealbumin levels10 mg/dl. Postoperative complications increased with lower prealbumin levels. All complications occurred in group of patients with prealbumin18 mg/dl (P=0.013). A significantly increased number of complications occurred in patients with prealbumin10 mg/dl (61.5% vs. 6.4%, P0.001, RR 9.6). All postoperative mortality in this series occurred in patients with prealbumin10 mg/dl (23.1% vs. 0%, P0.001). Patients whose prealbumin started low but was able to be raised to10 mg/dl by TPN did not have significantly increased complications or EBL compared to patients whose initial prealbumin was10 mg/dl (18.2% vs. 4.8%, P=0.95 and 570 vs. 600 ml, P=0.87).Significantly more blood loss, morbidity, and mortality occurred in patients with abnormal preoperative prealbumin. This was especially true in patients with a prealbumin10 mg/dl. With these significantly increased risks, patients with extremely poor nutritional status (prealbumin10 mg/dl) may be better served by neoadjuvant chemotherapy with interval cytoreductive surgery if nutrition improves.

Objective. The platinum-free interval (PFI) is an important entity in the treatment of women with epithelial ovarian cancer. The purpose of this study was to determine on clinical samples whether a taxane-free interval (TFI), as defined by in vitro extreme drug resistance assay, existed in women previously exposed to platinum and taxane chemotherapy. Methods. Records were examined from 2003 to 2006 to find all patients with epithelial ovarian cancer who had previous exposure to platinum and taxane therapy. Further examination was done to find all patients who underwent secondary cytoreduction and had their tumor submitted for extreme drug resistance assay. Results. Thirty-four women meeting the above criteria were found. The mean PFI was 25 months (median 18). The mean TFI was 27 months (median 20). Over 44% of the patients have been exposed to more than just a course of platinum and a course of a taxane. In patients having a PFI of ≥12 months, 38.8% had extreme drug resistance (EDR) to carboplatin and 41.9% EDR to cisplatin. Conversely, in patients having a TFI of ≥12 months, 89.7% had EDR to paclitaxel and 82.8% EDR to docetaxel. Conclusions. While only a small percentage have EDR to carboplatin and cisplatin after a PFI of ≥12 months, almost 90% of patients with a TFI ≥12 months showed EDR to paclitaxel in vitro .

Objective. To determine whether neoadjuvant cisplatin and 5-fluorouracil chemotherapy can be used to preserve the anal sphincter and/or urethra in patients with advanced vulvar cancer involving these sites. Methods. Fourteen patients with advanced vulvar cancer (1997–2003) involving the anal sphincter and/or urethra were given 3–4 cycles of neoadjuvant chemotherapy to attempt preservation of these pelvic structures rather than undergoing a primary pelvic exenteration. Following 3 cycles, a radical vulvectomy and groin lymph node dissection were planned. All patients had lesion size documented by measurement and photograph prior to and following chemotherapy. Results. The median age was 63 years (range 39–88). Thirteen patients received a median of 3 cycles (range 2–4) of neoadjuvant chemotherapy. Ten patients received cisplatin and 5-fluorouracil, while three received cisplatin alone. The median time from diagnosis to surgery was 77 days (range 54–143). All patients with cisplatin and 5-fluorouracil chemotherapy underwent surgery except one patient who had a synchronous renal cell carcinoma and died prior to surgery. Patients receiving cisplatin alone showed no measurable response, while all patients receiving cisplatin and 5-fluorouracil demonstrated at least a partial response. Two patients had no residual invasive carcinoma on final pathology. All patients receiving cisplatin and 5-fluorouracil followed by surgery are disease-free, while two of three receiving cisplatin have progressive disease. The anal sphincter and urethra were conserved in all patients receiving cisplatin and 5-fluorouracil. Conclusion. Neoadjuvant cisplatin and 5-fluorouracil in advanced vulvar cancer demonstrated a response rate of 100%. The anal sphincter and urethra were conserved in all patients receiving cisplatin and 5-fluorouracil. Responders are disease-free at this time. This response rate demonstrates superior activity of 5-fluorouracil in vulvar cancer and spares these patients the morbidity of exenteration or radiation.

Objective: The authors, using image analysis, previously demonstrated nuclear size and summed optical density to be independent prognostic indicators of recurrence in patients with endometrial carcinoma. The same tumors were analyzed by studying the optical features in the G0–G1 peak to see if this changed the values found as well as their importance as prognostic features at greater than 5 years of follow-up. Methods: Tumors from 74 consecutive patients, surgically treated, with endometrial cancer, were evaluated. Survival, depth of invasion, lymphvascular space invasion, FIGO stage, grade, histology were analyzed. DNA index, progesterone receptor status, as well as nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD) were evaluated. NUSZ, NUSH, and NUSD were quantified using image analysis. Results: Fifteen patients died from disease during the observation period of the study. Mean follow-up was 82 months with a median of 84 months. Forty-nine patients had stage I cancers, five stage II, 17 stage III, and three stage IV. NUSZ and NUSD were all significantly different between the original (entire cell cycle) and the re-measured (G0G1 only) values (both P

Background Malignant mixed mullerian tumors (MMMTs) of the ovary are a rare, aggressive subtype of ovarian cancer without a clear relationship to familial breast–ovarian cancer syndromes. Case We present the case of a woman with bilateral breast cancers who subsequently developed a stage IIIc MMMT of the ovary. The patient had a first-degree female relative with breast and ovarian cancer (not MMMT), as well as second- and third-degree female relatives each with bilateral breast cancers. BRCA1 and BRCA2 sequencing of germline DNA revealed no evidence of a heritable mutation. Discussion Ovarian MMMTs may be a hallmark of breast/ovarian cancer secondary to genetic risk independent of classic BRCA1/2 pathways.

Objectives. The purpose of this study was to determine the recurrence rate, survival, and pregnancy outcome in patients with Stage IA and Stage IC invasive epithelial ovarian cancer treated with unilateral adnexectomy. Methods. A multi-institutional retrospective investigation was undertaken to identify patients with Stage IA and IC epithelial ovarian cancer who were treated with fertility-sparing surgery. All patients with ovarian tumors of borderline malignancy were excluded. Long-term follow-up was obtained through tumor registries and telephone interviews. The time and sites of tumor recurrence, patient survival, and pregnancy outcomes were recorded for every patient. Results. Fifty two patients with Stage I epithelial ovarian cancer treated from 1965 to 2000 at 8 participating institutions were identified. Forty-two patients had Stage IA disease, and 10 had Stage IC cancers. Cell type was distributed as follows: mucinous, 25; serous, 10; endometrioid, 10; clear cell, 5; and mixed, 2. Histologic differentiation was as follows: grade 1, 38; grade 2, 9; and grade 3, 5. Twenty patients received adjuvant chemotherapy (mean 6 courses, range 3–12 courses). Patients received the following chemotherapeutic agents: cisplatin/taxol or carboplatin/taxol, 11; melphalan, 5; cisplatin and cyclophosphamide, 3; and single-agent cisplatin, 1. Eight patients had second-look laparotomies and all were negative. Duration of follow-up ranged from 6 to 426 months (median 68 months). Five patients developed tumor recurrence 8–78 months after initial surgery. Sites of recurrence were as follows: contralateral ovary, 3; peritoneum, 1; and lung, 1. Nine patients underwent subsequent hysterectomy and contralateral oophorectomy for benign disease. At present, 50 patients are alive without evidence of disease and 2 have died of disease 13 and 97 months after initial treatment. The estimated survival was 98% at 5 years and 93% at 10 years. Twenty-four patients attempted pregnancy and 17 (71%) conceived. These 17 patients had 26 term deliveries (no congenital anomalies noted) and 5 spontaneous abortions. Conclusion. The long-term survival of patients with Stage IA and IC epithelial ovarian cancer treated with unilateral adnexectomy is excellent. Fertility-sparing surgery should be considered as a treatment option in women with Stage I epithelial ovarian cancer who desire further childbearing.

Background: Although BRCA1 and BRCA2 play important roles in hereditary ovarian cancers, the extent of their role in sporadic ovarian cancers and their mechanisms of inactivation are not yet well understood. Our goal was to characterize BRCA2 mutations and mRNA expression in a group of ovarian tumors previously evaluated for BRCA1 mutations and mRNA expression. Methods: The tumors of 92 unrelated women with “ovarian” cancer (i.e., ovarian, peritoneal, or fallopian tube cancer) were screened for BRCA2 null mutations using a protein truncation test. Methylation-specific polymerase chain reaction (PCR) was used to examine the BRCA2 promoter for hypermethylation in tumors that did not express BRCA2 mRNA. All statistical tests were twosided. Results: Nine tumors had a germline (n = 5) or somatic (n = 4) BRCA2 mutation; each was associated with loss of heterozygosity. All of the somatic (1445delC, E880X, 4286del8, and 5783delT) and one of the germline (5984ins4) mutations were unique to this study. One tumor had somatic mutations in both BRCA1 and BRCA2. Two tumors are, to our knowledge, the first cases of germline BRCA2-associated peritoneal cancer. Twelve additional tumors lacked detectable BRCA2 mRNA, but the BRCA2 promoter was hypermethylated in only one of them, suggesting that other mechanisms effect transcriptional silencing of BRCA2. Tumors lacking BRCA1 mRNA were more likely to lack BRCA2 mRNA than tumors expressing BRCA1 mRNA (P