Associations of the gut microbiome with psychoneurological symptom cluster in women with gynecologic cancers: a longitudinal study.

PURPOSE: The present study aimed to evaluate the associations between the gut microbiome and psychoneurological symptoms (PNS) cluster in women with gynecologic cancers over time. METHODS: In this secondary data analysis, 19 women with cervical and endometrial cancers treated with radiotherapy were followed at pre-treatment, 6-8 weeks, and 6 months post-treatment. To measure symptoms, Functional Assessment of Cancer Therapy-General (FACT-G) and Patient Health Questionnaire-9 (PHQ-9) were used. An average Z score of at least three out of five symptoms was computed as the PNS cluster total score. Rectal swabs were also collected at the same time points and sequenced using 16S rRNA V4 regions. The Kruskal-Wallis and permutational multivariable analysis of variance tests were used to compare α- and ß-diversity between patients with high and low PNS cluster. The linear discriminant analysis effect size (LEfSe) tested taxa differences between study groups. Also, the linear mixed-effect model was used to evaluate the association of the gut microbiome and the PNS cluster over cancer treatment. RESULTS: The patients' mean age was 58 years, 47% Black, 52% single/divorced, and 66% had college or above education. Among the participants, 63% had endometrial cancer with stage I disease. There was a different taxonomy profile between patients with high and low PNS. Patients with high PNS had a lower α-diversity than those with low PNS (Shannon, p = 0.03, evenness, p = 0.03). The mixed effects model results showed that low α-diversity and abundance of Fusicatenibacter and Ruminococcus were associated with high PNS cluster over cancer treatment. CONCLUSION: The association between the gut microbiome and PNS cluster suggest that the gut microbiota plays a role in developing the PNS cluster. Future larger studies are required to shed light on the gut microbiota role in symptom development in gynecologic cancer patients.

Associations Between Social Determinants of Health and Psychoneurologic Symptom Clusters in Women With Gynecologic Cancers: A Longitudinal Study.

OBJECTIVES: To evaluate the associations between social determinants of health (SDOH) and psychoneurologic symptom (PNS) clusters in women with gynecologic cancers during cancer treatment. SAMPLE & SETTING: 67 women with gynecologic cancers who received radiation therapy were assessed at baseline, six to eight weeks after treatment, and six months after treatment at oncology clinics in Georgia. METHODS & VARIABLES: Fatigue, pain, sleep disturbances, cognitive impairment, and depressive symptoms were measured to determine a PNS cluster score. Associations between SDOH and PNS cluster scores were assessed using mixed-effect models. RESULTS: Larger mean PNS cluster scores were reported in individuals with less education, lower income, and unemployment, as well as in those living in more disadvantaged neighborhoods. IMPLICATIONS FOR NURSING: Individual- and community-level SDOH and their interactions were associated with more PNS clusters. Studying SDOH at multiple levels depicts how various social disadvantages can exacerbate poor health outcomes.

Automatic disease prediction from human gut metagenomic data using boosting GraphSAGE.

BACKGROUND: The human microbiome plays a critical role in maintaining human health. Due to the recent advances in high-throughput sequencing technologies, the microbiome profiles present in the human body have become publicly available. Hence, many works have been done to analyze human microbiome profiles. These works have identified that different microbiome profiles are present in healthy and sick individuals for different diseases. Recently, several computational methods have utilized the microbiome profiles to automatically diagnose and classify the host phenotype. RESULTS: In this work, a novel deep learning framework based on boosting GraphSAGE is proposed for automatic prediction of diseases from metagenomic data. The proposed framework has two main components, (a). Metagenomic Disease graph (MD-graph) construction module, (b). Disease prediction Network (DP-Net) module. The graph construction module constructs a graph by considering each metagenomic sample as a node in the graph. The graph captures the relationship between the samples using a proximity measure. The DP-Net consists of a boosting GraphSAGE model which predicts the status of a sample as sick or healthy. The effectiveness of the proposed method is verified using real and synthetic datasets corresponding to diseases like inflammatory bowel disease and colorectal cancer. The proposed model achieved a highest AUC of 93%, Accuracy of 95%, F1-score of 95%, AUPRC of 95% for the real inflammatory bowel disease dataset and a best AUC of 90%, Accuracy of 91%, F1-score of 87% and AUPRC of 93% for the real colorectal cancer dataset. CONCLUSION: The proposed framework outperforms other machine learning and deep learning models in terms of classification accuracy, AUC, F1-score and AUPRC for both synthetic and real metagenomic data.

Incidence and predictors of toxicity in the management of vulvar squamous cell carcinoma treated with radiation therapy.

Purpose/Objective: Given the rarity of vulvar cancer, data on the incidence of acute and late severe toxicity and patients' symptom burden from radiotherapy (RT) are lacking. Materials/Methods: This multi-center, single-institution study included patients with vulvar squamous cell carcinoma treated with curative intent RT between 2009 and 2020. Treatment-related acute and late grade ≥ 3 toxicities and late patient subjective symptoms (PSS) were recorded. Results: Forty-two patients with predominantly stage III/IV disease (n = 25, 59.5 %) were treated with either definitive (n = 25, 59.5 %) or adjuvant (n = 17, 40.5 %) external beam RT to a median dose of 64 Gy and 59.4 Gy, respectively. Five patients received a brachytherapy boost with a median total dose of 84.3 Gy in 2 Gy-equivalent dose (EQD2). Intensity-modulated RT was used in 37 (88.1 %) of patients, and 25 patients (59.5 %) received concurrent chemotherapy. Median follow-up was 27 months. Acute grade ≥ 3 toxicity occurred in 17 patients (40.5 %), including 13 (31.0 %) acute grade 3 skin events. No factors, including total RT dose (p = 0.951), were associated with acute skin toxicity. Eleven (27.5 %) patients developed late grade ≥ 3 toxicity events, including 10 (23.8 %) late grade ≥ 3 skin toxicity events. Patients with late grade ≥ 3 skin toxicity had a higher mean body-mass index (33.0 vs 28.2 kg/m2; p = 0.009). Common late PSS included vaginal pain (n = 15, 35.7 %), skin fibrosis (n = 10, 23.8 %), and requirement of long-term opiates (n = 12, 28.6 %). Conclusion: RT for vulvar cancer is associated with considerable rates of severe acute and late toxicity and PSS burden. Larger studies are needed to identify risk factors, explore toxicity mitigation strategies, and assess patient-reported outcomes.

Vermiremediation of allopathic pharmaceutical industry sludge amended with cattle dung employing Eisenia fetida.

The present study aims to vermiremediate allopathic pharmaceutical industry sludge (AS) amended with cattle dung (CD), in different feed mixtures (AS:CD) i.e (AS0) 0:100 [Positive control], (AS25) 25:75, (AS50) 50:50, (AS75) 75:25 and (AS100) 100:0 [Negative Control] for 180 days using earthworm Eisenia fetida. The earthworms could thrive and grow well up to the AS75 feed mixture. In the final vermicompost, there were significant decreases in electrical conductivity (29.18-18.70%), total organic carbon (47.48-22.39%), total organic matter (47.47-22.36%), and C: N ratio (78.15-54.59%). While, significant increases in pH (9.06-16.47%), total Kjeldahl nitrogen (69.57-139.58%), total available phosphorus (30.30-81.56%), total potassium (8.92-22.22%), and total sodium (50.56-62.12%). The heavy metals like Cr (50-18.60%), Cd (100-75%), Pb (57.14-40%), and Ni (100-50%) were decreased, whereas Zn (8.37-53.77%), Fe (199.03-254.27%), and Cu (12.90-100%) increased significantly. The toxicity of the final vermicompost was shown to be lower in the Genotoxicity analysis, with values ranging between (76-42.33%). The germination index (GI) of Mung bean (Vigna radiata) showed a value ranging between 155.02 and 175.90%. Scanning electron microscopy (SEM) analysis showed irregularities with high porosity of texture in the final vermicompost than in initial mixtures. Fourier Transform-Infrared Spectroscopy (FT-IR) spectra of final vermicompost had low peak intensities than the initial samples. The AS50 feed mixture was the most favorable for the growth and fecundity of Eisenia fetida, emphasizing the role of cattle dung in the vermicomposting process. Thus, it can be inferred that a cost-effective and eco-friendly method (vermicomposting) with the proper amendment of cattle dung and employing Eisenia fetida could transform allopathic sludge into a nutrient-rich, detoxified, stable, and mature vermicompost for agricultural purposes and further could serve as a stepping stone in the allopathic pharmaceutical industry sludge management strategies in the future.

Thirty-day Postoperative Adverse Events in Minimally Invasive versus Open Abdominal Radical Hysterectomy for Early-stage Cervical Cancer.

STUDY OBJECTIVE: To identify the incidence, type, and grade of postoperative adverse events in minimally invasive radical hysterectomy vs abdominal radical hysterectomy (ARH) for patients with early-stage cervical cancer and determine risk factors associated with these adverse events. DESIGN: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was queried to identify patients with early-stage cervical cancer undergoing radical hysterectomy. Multivariable logistic regression was used to assess risk factors associated with adverse postoperative outcomes among patients undergoing radical hysterectomy. SETTING: ACS NSQIP participating institutions within the United States. PATIENTS: Patients were collected from the ACS NSQIP databases (2014-2017) undergoing radical hysterectomy for early-stage cervical cancer. INTERVENTIONS: N/A MEASUREMENTS AND MAIN RESULTS: ARH had a significantly increased incidence of any 30-day postoperative adverse event compared with minimally invasive radical hysterectomy (31.2% vs 19.9%, p <.001). There was a higher incidence of surgical site infection, both deep and superficial, and blood transfusions in ARH. On multivariable logistic regression, the abdominal surgical approach was the only risk factor significantly associated with any postoperative adverse event (odds ratio, 1.4; confidence interval, 1.1-1.9; p = .018; 95% CIs). CONCLUSIONS: In this study, the abdominal surgical approach for radical hysterectomy in early-stage cervical cancer was associated with a higher incidence of postoperative adverse events than the minimally invasive approach.

Changes in the Vaginal Microbiome and Associated Toxicities Following Radiation Therapy for Gynecologic Cancers.

Postmenopausal women often suffer from vaginal symptoms associated with atrophic vaginitis. Additionally, gynecologic cancer survivors may live for decades with additional, clinically significant, persistent vaginal toxicities caused by cancer therapies, including pain, dyspareunia, and sexual dysfunction. The vaginal microbiome (VM) has been previously linked with vaginal symptoms related to menopause (i.e. dryness). Our previous work showed that gynecologic cancer patients exhibit distinct VM profiles from healthy women, with low abundance of lactobacilli and prevalence of multiple opportunistic pathogenic bacteria. Here we explore the association between the dynamics and structure of the vaginal microbiome with the manifestation and persistence of vaginal symptoms, during one year after completion of cancer therapies, while controlling for clinical and sociodemographic factors. We compared cross-sectionally the vaginal microbiome in 134 women, 64 gynecologic patients treated with radiotherapy and 68 healthy controls, and we longitudinally followed a subset of 52 women quarterly (4 times in a year: pre-radiation therapy, 2, 6 and 12 months post-therapy). Differences among the VM profiles of cancer and healthy women were more pronounced with the progression of time. Cancer patients had higher diversity VMs and a variety of vaginal community types (CTs) that are not dominated by Lactobacilli, with extensive VM variation between individuals. Additionally, cancer patients exhibit highly unstable VMs (based on Bray-Curtis distances) compared to healthy controls. Vaginal symptoms prevalent in cancer patients included vaginal pain (40%), hemorrhage (35%), vaginismus (28%) and inflammation (20%), while symptoms such as dryness (45%), lack of lubrication (33%) and dyspareunia (32%) were equally or more prominent in healthy women at baseline. However, 24% of cancer patients experienced persistent symptoms at all time points, as opposed to 12% of healthy women. Symptom persistence was strongly inversely correlated with VM stability; for example, patients with persistent dryness or abnormally high pH have the most unstable microbiomes. Associations were identified between vaginal symptoms and individual bacterial taxa, including: Prevotella with vaginal dryness, Delftia with pain following vaginal intercourse, and Gemillaceaea with low levels of lubrication during intercourse. Taken together our results indicate that gynecologic cancer therapy is associated with reduced vaginal microbiome stability and vaginal symptom persistence.

ACR Appropriateness Criteria® Staging and Follow-up of Primary Vaginal Cancer.

Primary vaginal cancer is rare, comprising 1% to 2% of gynecologic malignancies and 20% of all malignancies involving the vagina. More frequently, the vagina is involved secondarily by direct invasion from malignancies originating in adjacent organs or by metastases from other pelvic or extrapelvic primary malignancies. Data on the use of imaging in vaginal cancer are sparse. Insights are derived from the study of imaging in cervical cancer and have reasonable generalizability to vaginal cancer due to similar tumor biology. Given the trend toward definitive chemoradiation for both cancers in all but early stage lesions, principles of postchemoradiation tumor response evaluation are largely analogous. Accordingly, many of the recommendations outlined here are informed by principles translated from the literature on cervical cancer. For pretreatment assessment of local tumor burden and in the case of recurrent vaginal cancer, MRI is the preferred imaging modality. PET/CT has demonstrated utility for the detection of nodal metastatic and unexpected distant metastatic disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Staging and Follow-up of Vulvar Cancer.

Vulvar cancer is an uncommon gynecologic tumor and one of several human papillomavirus-associated malignancies. Squamous cell carcinoma is the most prevalent histologic subtype of vulvar cancer, accounting for the majority of cases. Imaging plays an important role in managing vulvar cancer. At initial diagnosis, imaging is useful to assess the size and extent of primary tumor and to evaluate the status of inguinofemoral lymph nodes. If recurrent disease is suspected, imaging is essential to demonstrate local extent of tumor and to identify lymph node and distant metastases. In this publication, we summarize the recent literature and describe the panel's recommendations about the appropriate use of imaging for various phases of patient management including initial staging, surveillance, and restaging of vulvar cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR appropriateness criteria staging and follow-up of vulvar cancer

Vulvar cancer is an uncommon gynecologic tumor and one of several human papillomavirus-associated malignancies. Squamous cell carcinoma is the most prevalent histologic subtype of vulvar cancer, accounting for the majority of cases. Imaging plays an important role in managing vulvar cancer. At initial diagnosis, imaging is useful to assess the size and extent of primary tumor and to evaluate the status of inguinofemoral lymph nodes. If recurrent disease is suspected, imaging is essential to demonstrate local extent of tumor and to identify lymph node and distant metastases. In this publication, we summarize the recent literature and describe the panel's recommendations about the appropriate use of imaging for various phases of patient management including initial staging, surveillance, and restaging of vulvar cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Comparisons of Depression, Sexual Function, and Quality of Life Between Women With Gynecological Cancers and Race-Matched Healthy Controls.

BACKGROUND: Although higher incidence and mortality of gynecological cancer (GynCa) are documented in black compared with white women, few studies have documented quality of life (QOL) or healthy control comparisons. OBJECTIVE: This study compared depression, sexual function, and QOL between patients with GynCa and race-matched healthy controls. METHODS: Patients with GynCa and healthy controls completed the Patient Health Questionnaire-9, Female Sexual Function Index, and Functional Assessment of Cancer Therapy-General measures at baseline; GynCa patients were assessed again at 6 months post-radiation therapy (RT). RESULTS: Analyses included 84 participants (51% white, 49% black), including 28 GynCa patients and 56 controls with similar marital status. Compared with healthy controls, patients were younger, had a higher body mass index, and had more depression (P = .01); 82% of the patients and 71% of the healthy controls met criteria for sexual dysfunction at baseline (P = .29). Patients pre-RT had greater sexual dysfunction and lower QOL (P = .001) than controls did; patients at 6-month post-RT showed improved sexual function scores compared with pre-RT, with similar results to controls. White GynCa patients reported less sexual desire (P = .02), more pain (P = .05), and lower total Female Sexual Function Index scores (P = .01) than did black GynCa patients. Both black and white GynCa patients reported lower total QOL than their race-matched controls did (P = .07 and P = .002). CONCLUSIONS: Women with GynCa reported more depression and lower QOL than did healthy controls pre-RT. Among GynCa patients, white women had more sexual dysfunction than black women did. IMPLICATIONS FOR PRACTICE: The differences in sexual dysfunction between white and black women with GynCa suggest developing guidelines directing routine sexual assessment and rehabilitation in women treated for GynCa.

Folate Receptor Alpha Is Preferentially Expressed in the Carcinoma Component of Endometrial Carcinosarcomas: A Potential Target for Adjuvant Therapy.

Carcinosarcomas (CSs) of the endometrium are biphasic malignancies, composed of high-grade carcinomatous and sarcomatous components. Surgical stage and pathologic characteristics are the most important prognostic findings, with a 5-yr survival of 15% to 30% in advance stage disease. Folate receptor alpha (FRA) overexpression has been observed in endometrial carcinomas and not yet studied in CSs. This study evaluates semiquantitative expression of FRA in both carcinomatous and sarcomatous components of CSs on whole tissue sections. Immunohistochemistry for FRA expression was performed and extent and intensity of staining were recorded for each case for both histologic components. A total of 46 cases were stained for FRA. The majority of these (40/46, 87%) showed FRA staining at variable intensity in the carcinomatous component, stronger in serous carcinomas and high-grade endometrioid, while only a small subset of tumors demonstrated weak staining in the sarcomatous component (2/46, 4.35%). CS is known to be associated with poor prognosis and adjuvant therapy is recommended even in low stage disease. Serous and high-grade endometrioid carcinomas are the most common carcinomatous components of CSs and are known to show consistently high FRA expression. Folate plays a role in tumor cell migration and loss of cellular adhesion, which are key steps in epithelial-mesenchymal transition, the process by which CS develops from carcinoma cells. Our study shows expression of FRA in the carcinomatous component of almost all CS cases (87%), further favoring FRA as a target for adjuvant treatment. While expression of FRA in the sarcomatous component was rarely observed, the carcinomatous component being associated with metastatic potential underscores the importance of anti-FRA therapy for systemic disease control.

Do High Rates of Atypical Glandular Cells Correlate With Higher Incidence of Disease in a Large Safety Net Hospital.

OBJECTIVE: The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. MATERIALS AND METHODS: Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. RESULTS: Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. CONCLUSIONS: This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.

Primary colonic extrauterine endometrial stromal sarcoma: A case and review of the literature.

•Primary colonic extrauterine endometrial stromal sarcoma is a rare entity and diagnosis of this tumor can be challenging.•There is a common gene translocation specific to the tumors, our case was confirmed by identifying it.•Classifying these tumors correctly is important for treatment.

Comparison of vaginal microbiota in gynecologic cancer patients pre- and post-radiation therapy and healthy women.

BACKGROUND: While the importance of commensal microbes in vaginal health is well appreciated, little is known about the effects of gynecological cancer (GynCa) and radiation therapy (RT) on the vaginal microbiome (VM) of postmenopausal women. METHODS: We studied women with GynCa, pre- (N = 65) and post-RT (N = 25) and a group of healthy controls (N = 67) by sequencing the V4 region of the 16S rRNA gene from vaginal swabs and compared the diversity and composition of VMs between the three groups accounting for potential confounding factors in multivariate analysis of variance. RESULTS: Comparisons of cancer vs healthy groups revealed that Lactobacillus and Bifidobacterium have significantly higher relative abundance in the healthy group, while the cancer group was enriched in 16 phylogroups associated with bacterial vaginosis (BV) and inflammation, including Sneathia, Prevotella, Peptoniphilus, Fusobacterium, Anaerococcus, Dialister, Moryella, and Peptostreptococcus. In our sample, RT affected the α-diversity and correlated with higher abundance of typically rare VM species, including several members of the Lacnospiraceae family, a taxon previously linked to vaginal dysbiosis. In addition to cancer and treatment modalities, age and vaginal pH were identified as significant parameters that structure the VM. CONCLUSIONS: This is among the first reports identifying VM changes among postmenopausal women with cancer. RT alone seems to affect several phylogroups (12 bacterial genera), while gynecological cancer and its treatment modalities are associated with even greater significant shifts in the vaginal microbiota including the enrichment of opportunistic bacterial pathogens, which warrants further attention.

Generation of a functional, semisynthetic [FeFe]-hydrogenase in a photosynthetic microorganism.

[FeFe]-Hydrogenases are hydrogen producing metalloenzymes with excellent catalytic capacities, highly relevant in the context of a future hydrogen economy. Here we demonstrate the synthetic activation of a heterologously expressed [FeFe]-hydrogenase in living cells of Synechocystis PCC 6803, a photoautotrophic microbial chassis with high potential for biotechnological energy applications. H2-Evolution assays clearly show that the non-native, semi-synthetic enzyme links to the native metabolism in living cells.

Folate Receptor Alpha Expression in Platinum Resistant/Refractory Ovarian Carcinomas and Primary Endocervical Adenocarcinomas.

INTRODUCTION: Treatment of advanced stage ovarian carcinoma is challenging, and despite surgical treatment and chemotherapy, the 5-year survival rate is estimated around 30%. Early recurrence and resistance to platinum-based chemotherapy are associated with poor prognosis and limited response to available second-line chemotherapy. The relative incidence of endocervical adenocarcinoma (EAC) compared with squamous cell carcinoma is increasing. Although the first-line treatment modality for early stage EAC is surgical resection, for locally advanced disease chemoradiation or neoadjuvant chemotherapy is used. Recently, folate along with its receptor alpha (FRA) has been studied as a potential target in gynecologic malignancy. The objective of this study was to elucidate FRA expression in chemotherapy resistant ovarian cancer and primary EAC. METHODS: FRA expression was evaluated in tissue samples in an epithelial ovarian tumor microarray and 2 study groups: platinum resistant ovarian cancer and primary EAC. Staining intensity was analyzed with a semiquantitative staining algorithm. RESULTS: FRA expression was positive in 32 of 40 (80%) ovarian tumors in the control group. In the platinum resistant ovarian cancer group, FRA was expressed in all 30 samples with moderate to strong staining. None of the EAC samples stained positive for FRA expression. CONCLUSIONS: FRA expression occurs frequently in epithelial ovarian cancer. Our data supports that FRA expressions are maintained after chemotherapy treatment. Folate targeted therapies may be most useful in patients with chemotherapy resistant disease based on high levels of FRA expression in these tumors. There is likely no benefit to folate therapy as an adjuvant treatment in EAC.