Fallopian Tube Specimens Research Articles

Tubal pathologies in benign hysterectomies

Fallopian tube is a pair of hollow, muscular tubes that are located at the upper margin of the uterus's broad ligament on each side of the uterus. The most frequent illness among women in the reproductive age range is salpingitis, where about 11% of females are affected. Para tubal cysts, hydrosalpinx, endometriosis and walthard cell nests are one of the common lesions of the fallopian tubes. To evaluate the tubal pathologies in benign hysterectomies done in a tertiary care hospital. We conducted a retrospective observational study for 15 months from October 2022 to December 2023 on 110 women who underwent hysterectomies along with salpingectomies or undertook the procedure as a part of tuboovarian masses in our hospital. These surgically resected specimens of fallopian tube which were received during the study period were included. Haemotoxylin and eosin stained histopathology slides of these cases were examined for a detailed analysis of histological patterns of various fallopian tube lesions. The data was represented in percentages and frequencies.: Among the 110 study participants, the minimum age of the women were 35 years and the maximum age was 64 years. The most common diagnosis in our study was Abnormal uterine bleeding (AUB) which was among 87 (78.8%) of the patients, followed by ovarian cyst (8.1%) and fibroid (6.3%). The tubal pathology was abnormal in 54.5% of the study participants. Majority of the abnormal tubal pathology was found to be paratubal cyst corresponding to 30.6% and 18% in the right and left fallopian tubes respectively followed by hydrosalphinx in the right fallopian tubes corresponding to 10.8%. This study concluded that more than 50% of fallopian tubes had aberrant diseases. Thus, a salpingectomy along with hysterectomy is beneficial to the patient in order to prevent further morbidity.

Do we more often opt for conservative management of ovarian tumors after changing the Dutch national guideline on enlarged ovaries? A nationwide cohort study.

Increasing evidence shows that conservative management of ovarian tumors classified as benign, based on ultrasound assessment, is safe. Therefore, conservative management has been adopted as the preferred strategy for certain ovarian tumors assessed as benign in the Dutch national guideline on enlarged ovaries in 2013. The aim of this study was to examine whether implementation of this guideline has led to changes in the number of women/100 000 women undergoing surgery for an ovarian tumor in the Netherlands. Histopathology reports were requested for all examinations of ovarian and fallopian tube specimens (including cyst enucleations) registered in Palga, the Dutch nationwide pathology databank, from 2011 (before guideline adaptation) and 2019 (after guideline adaptation). Reports on prophylactically removed adnexa, removal for other primary tumors (e.g., endometrial carcinoma), and for patients under 18 years of age, were excluded from the analysis. Interobserver agreement for the inclusion and classification of reports was assessed using Cohen's Kappa analysis. A total of 34 932 reports were retrieved, 13 917 of which were included in the analysis. In 2011 and 2019, respectively, 96.3/100 000 versus 68.8/100 000 women aged ≥18 underwent surgery for benign ovarian tumors, and 19.6/100 000 versus 18.3/100 000 for borderline and malignant tumors combined. The number of women/100 000 who had surgery for a benign ovarian tumor per 100 000 women declined by 28.5% (p < 0.001) between 2011 and 2019. The largest difference between 2011 and 2019 was observed in the number of women per 100 000 women who underwent surgery for a serous cystadenoma (-40.7%; 20.8/100 000 vs. 12.3/100 000), followed by endometrioma (-33.2%; 14.7/100 000 vs. 9.8/100 000), simple epithelial cyst (-57.3%; 8.4/100 000 vs. 3.6/100 000), and corpus luteum cyst (-57.0%; 4.0/100 000 vs. 1.7/100 000). Cohen's Kappa for the interobserver agreement was 0.96. The number of women/100 000 undergoing surgery for a benign ovarian tumor has substantially decreased in the Netherlands when comparing data before and after implementation of the national guideline in 2013, while the number of women/100 000 undergoing surgery for a malignant or borderline tumor remained the same. These findings suggest successful implementation of the updated guideline, and a measurable effect on increased adoption of conservative management for benign-looking ovarian tumors.

Natural Killer Cell Dysfunction in Premenopausal BRCA1 Mutation Carriers: A Potential Mechanism for Ovarian Carcinogenesis.

Tissue-specificity for fimbrial fallopian tube ovarian carcinogenesis remains largely unknown in BRCA1 mutation carriers. We aimed to assess the cell autonomous and cell-nonautonomous implications of a germline BRCA1 mutation in the context of cancer immunosurveillance of CD3- CD56+ natural killer (NK) cells. Premenopausal BRCA1 mutation carriers versus age-matched non-carriers were compared. Daily urinary 5β-pregnanediol levels were used to determine progesterone metabolomics across an ovarian cycle. Using peripherally acquired NK cells the cell-mediated cytotoxicity of tumor targets (OVCAR-3, K-562) was determined using live cellular impedance (xCELLigence®) and multicolor flow cytometry. Hypoxia-inducible factor 1-alpha (HIF-1α) immunohistochemistry of cancer-free fallopian tube specimens allowed a comparison of proximal versus distal portions. Utilizing these findings the role of environmental factors relevant to the fimbrial fallopian tube (progesterone, hypoxia) on NK cell functional activity were studied in an ovarian phase-specific manner. BRCA1 mutation carriers demonstrate a differential progesterone metabolome with a phase-specific reduction of peripheral NK cell functional activity. Progesterone exposure further impairs NK cell-mediated cytotoxicity in a dose-dependent manner, which is reversed with the addition of mifepristone (1.25 µM). The fimbrial fallopian tube demonstrated significantly higher HIF-1α staining, particularly in BRCA1 mutation carriers, reflecting a site-specific 'hypoxic niche'. Exposure to hypoxic conditions (1% O2) can further impair tumor cytotoxicity in high-risk carriers. Phase-specific differential NK cell activity in BRCA1 mutation carriers, either systemically or locally, may favor site-specific pre-invasive carcinogenesis. These cumulative effects across a reproductive lifecycle in high-risk carriers can have a detrimental effect further supporting epidemiological evidence for ovulation inhibition.

Pattern and Frequency of Fallopian Tube Lesions in Resected Hysterectomy Specimens

Introduction: The fallopian tube or salpinx has been named after scientist Gabrielis Fallopus, who was the first to describe the fallopian tube precisely. Fallopian tubes are though very common surgical specimens but are rarely studied. Inflammatory diseases of fallopian tubes and infertility due to various tubal factors are one most common disease observed in females. Aims and Objectives: To evaluate the spectrum of fallopian tube lesions in surgically resected hysterectomy specimens grossly and on histopathology. To study the frequency of various histopathological lesions of fallopian tubes. Material and Methods: The prospective study was conducted over one year, and 316 Right fallopian tubes and 314 left fallopian tube specimens’ histopathology were analysed. Results: In this study, it was observed that 96.52% of right fallopian tubes and 95.86% of left fallopian tubes were normal on histology. The most common histopathological lesions observed were salpingitis and Para tubal cysts. Conclusion: Various histopathological lesions can be observed in fallopian tubes. Although Malignancies of fallopian tubes are rare, they must be subjected to histopathological examination to evaluate various pathological lesions. Keywords: fallopian tube, salpinx, resected hysterectomy

Fallopian tube cytology as a diagnostic tool for adnexal malignancy: the CytoSaLPs score.

During the past decade, the theory that high-grade extrauterine pelvic tumors originate from the fallopian tube has been strongly suggested. Our study aims to illuminate the possible role of tubal cytology as an accessory identification tool for gynecologic extrauterine malignancies, allowing in the long term the implementation of population-level cytologic tube evaluation during all benign gynecologic surgeries that do not result in salpingectomy. We exvivo collect salpingeal epithelial cells from the fibria directly from fresh fallopian tube specimens from women undergoing salpingectomy for any indication. The cytomorphologic characteristics of the salpingeal cells are subsequently evaluated and categorized into malignant and non-malignant. Finally, the ipsilateral adnexa are examined with the SEE-FIM (Sectioning and Extensively Examining the FIMbriated End) protocol and the pathology reports are corelated with the cytologic findings. Our research protocol is ongoing and is designed to include a total of 300 patients in order to confirm the sensitivity and specificity of salpingeal cytology as a method in the early diagnosis of extrauterine gynecologic malignancies. So far, we have obtained 343 salpingeal brushings from a total of 214 patients. The sensitivity of cytology regarding distinguishing malignant from non-malignant tumors is 69.64% (95% CI: 55.90%-81.22%), and its specificity 75.96% (95% CI: 70.59%-80.79%). Cytology's positive predictive value (PPV) is 16.33% (95% CI: 12.57%-20.67%), while the negative predictive value (NPP) reached 92.77% (95% CI: 89.56%-95.04%). In general, the diagnostic accuracy of the cytologic evaluation reaches 74.93% (95% CI: 66.99%-79.43%). Salpingeal cytomorphologic evaluation appears to be a promising method for early detection of adnexal cancer.

Uterine and Ovarian Histopathology in Transmasculine and Nonbinary Patients on Testosterone Compared to Cisgender Control Patients [ID: 1381367

INTRODUCTION: Hormonal treatment is a critical aspect of health care for transgender and nonbinary patients, but scientific literature describing ovarian and uterine histopathology in the setting of testosterone therapy remains limited and conflicted. METHODS: After IRB approval and patient consent, uterine and ovarian histopathology was prospectively evaluated in 22 gender-diverse patients on testosterone compared with 21 premenopausal cisgender controls not on hormones undergoing hysterectomy. RESULTS: Average duration of testosterone administration was 54.9 months. Average age was 30 years in the testosterone group and 40.6 years in the control group. Average body mass index was 28 kg/m2 in the testosterone group and 31 kg/m2 in the control group. 18 (82%) patients in the testosterone group had inactive/atrophic endometria, compared with 2 (10%) in the control group. 4 (18%) patients in the testosterone group had proliferative endometria, compared to 10 (48%) in the control group. No patients on testosterone had secretory endometrium, compared to 6 (29%) in the control group. Leiomyoma were noted for 5 (23%) in the testosterone group and 4 (19%) in the control group. Adenomyosis was present in 1 (5%) in the testosterone group, compared to 5 (24%) in the control group. Low rates of preoperative cervical dysplasia were reported in both groups. All cervical and fallopian tube specimens in both groups were benign. CONCLUSION: Compared to a cisgender control group, patients on long-term testosterone therapy were more likely to have inactive/atrophic endometrium. Increasing our knowledge of the effects of testosterone has implications for preoperative surgical assessment and surveillance for patients not undergoing surgery.

Expression and T cell regulatory action of the PD-1 immune checkpoint in the ovary and fallopian tube.

Immune cell trafficking and surveillance within the ovary and fallopian tube are thought to impact fertility and also tumorigenesis in those organs. However, little is known of how native cells of the ovary and fallopian tube interact with resident immune cells. Interaction of the Programmed Cell Death Protein-1 (PD-1/PDCD-1/CD279) checkpoint with PD-L1 is associated with downregulated immune response. We have begun to address the question of whether PD-1 ligand or its receptors (PD-L1/-L2) can regulate immune cell function in these tissues of the female reproductive tract. PD-1 and ligand protein expression was evaluated in human ovary and fallopian tube specimens, the latter of which included stages of tubal cell transformation and early tumorigenesis. Ovarian expression analysis included the determination of the proteins in human follicular fluid (HFF) specimens collected during in vitro fertilization procedures. Finally, checkpoint bioactivity of HFF was determined by treatment of separately-isolated human T cells and the measurement of interferon gamma (IFNγ). We show that membrane bound and soluble variants of PD-1 and ligands are expressed by permanent constituent cell types of the human ovary and fallopian tube, including granulosa cells and oocytes. PD-1 and soluble ligands were present in HFF at bioactive levels that control T cell PD-1 activation and IFNγ production; full-length checkpoint proteins were found to be highly enriched in HFF exosome fractions. The detection of PD-1 checkpoint proteins in the human ovary and fallopian tube suggests that the pathway is involved in immunomodulation during folliculogenesis, the window of ovulation, and subsequent egg and embryo immune-privilege. Immunomodulatory action of receptor and ligands in HFF exosomes is suggestive of an acute checkpoint role during ovulation. This is the first study in the role of PD-1 checkpoint proteins in human tubo-ovarian specimens and the first examination of its potential regulatory action in the contexts of normal and assisted reproduction.

Quantification of ovarian lesion and fallopian tube vasculature using optical-resolution photoacoustic microscopy

The heterogeneity in the pathological and clinical manifestations of ovarian cancer is a major hurdle impeding early and accurate diagnosis. A host of imaging modalities, including Doppler ultrasound, MRI, and CT, have been investigated to improve the assessment of ovarian lesions. We hypothesized that pathologic conditions might affect the ovarian vasculature and that these changes might be detectable by optical-resolution photoacoustic microscopy (OR-PAM). In our previous work, we developed a benchtop OR-PAM and demonstrated it on a limited set of ovarian and fallopian tube specimens. In this study, we collected data from over 50 patients, supporting a more robust statistical analysis. We then developed an efficient custom analysis pipeline for characterizing the vascular features of the samples, including the mean vessel diameter, vascular density, global vascular directionality, local vascular definition, and local vascular tortuosity/branchedness. Phantom studies using carbon fibers showed that our algorithm was accurate within an acceptable error range. Between normal ovaries and normal fallopian tubes, we observed significant differences in five of six extracted vascular features. Further, we showed that distinct subsets of vascular features could distinguish normal ovaries from cystic, fibrous, and malignant ovarian lesions. In addition, a statistically significant difference was found in the mean vascular tortuosity/branchedness values of normal and abnormal tubes. The findings support the proposition that OR-PAM can help distinguish the severity of tubal and ovarian pathologies.

Abstract 5833: Functional characterization of TP53 mutations in human fallopian tube secretory epithelial cells

Abstract Ovarian cancer is the fifth leading cause of cancer-related death in women and mainly develops in older women. High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer and recently has been shown to arise from the distal end of the fallopian tube. About 96% of HGSC cases were found to contain mutations in TP53 and missense mutation was the most frequent type. It is known that TP53 mutation is an early event occurred in HGSC and may drive tumorigenesis. Different TP53 mutations have been reported to promote cell survival, metastatic potential or tumorigenicity. However, the roles of TP53 mutations and the underlying molecular mechanisms have not been satisfactorily understood in HGSC. In order to functionally characterize TP53 mutations in a systematic approach, primary human fallopian tube secretory epithelial cells (FTSECs) from normal fallopian tube specimens were used. We isolated and transduced FTSECs with hTERT for extending cell lifespan. Afterwards, both overexpression and knock down experiments were performed. According to the IARC TP53 Database, we selected four TP53 hotspot mutations found in ovarian cancer patients for further investigation. The mutant TP53, including R175H, Y220C, R273C, and R273H, were expressed in FTSECs. Meanwhile, knock down was achieved by introducing shRNAs targeting TP53. The transduced cells were subjected to RNA sequencing experiments to identify the significantly influenced genes and signaling pathways. The candidate genes and pathways will be validated in FTSECs and a panel of ovarian cancer cell lines. Functional assays, such as cell viability assay, migration/invasion assay, and metabolism assay, will be performed to study the effects of TP53 mutations. The results can provide further understanding of TP53 mutations and the downstream signaling in HGSC tumorigenesis. Citation Format: Ya-Yun Cheng, Denise Prosser, Liudmila Velikokhatnaya, Anna Lokshin. Functional characterization of TP53 mutations in human fallopian tube secretory epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5833.

Spectrum of Lesions in the Fallopian Tubes – A Histopathogical Study

Introduction: The Fallopian tubes are a pair of narrow tubular structures connecting the ovary and the uterus. It is usually the site of fertilization and plays a very important role in the fusion of the sperm and ovary and helps in movement of the fertilized zygote to the uterus. Even though being an organ of very small size the importance of the variety of lesions occurring in the fallopian tubes is often not considered. Biopsies of the fallopian tubes are taken to show the different lesions found in the tubes.&#x0D; Aim: The main aim of the study is to study the spectrum of lesions occurring in the fallopian tubes and correlation of these findings with its clinical parameters.&#x0D; Study Design: This is a retrospective descriptive study&#x0D; Place and Duration of Study: Department of Pathology, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai between June 2019- December 2019.&#x0D; Methodology: A retrospective study of all the fallopian tube specimens sent for routine histopathological analysis over a period of 6 months was carried out. The different pathological lesions were observed from the relevant clinical data and the correlation with its clinical parameters was done.&#x0D; Results: A sample size of 77 specimens was collected among which the commonest age group which was found to have the highest number of lesions was between 26-30 years. This was found to be in correlation to the reproductive age group of women. The most common form of pathological lesion observed was ectopic pregnancy (about 46% of total pathological lesions), followed by Paratubal cysts (23%), Hydrosalpinx (15%) and Hematosalpinx (8%). Cystadenoma was the only benign tumor observed in this study and constituted 8% of the total pathological lesions.&#x0D; Conclusion: This study shows the importance of histopathological examination of all fallopian tube specimens with or without abnormal findings.

#ESHREjc report: are fallopian tubes the unsung hero of reproduction?

The fallopian tubes’ role in reproduction has often been simplified into a dichotomy between open, permitting spontaneous conception, and closed, warranting IVF. The January 2021 edition of the ESHRE Journal Club (#ESHREjc) (Lambalk et al., 2021) featured a study published in Human Reproduction that adds to the growing body of evidence that tubal physiology is more complex and has more clinical implications than commonly thought (Jackson-Bey et al., 2020). The authors studied human fallopian tube specimens in static and dynamic conditions in microfluidic devices to assess the potential influence of a high testosterone concentration versus a regular hormonal milieu. Their results, displaying slower cilia beating and inhibited estrogen signaling in the group exposed to higher testosterone levels, underline how we are only just starting to open Pandora’s box of tubal physiology. Indeed, tubes are part of a complex environment: tubal secretions influence embryo...

Reply: Exposure of human fallopian tube epithelium to elevated testosterone results in alteration of cilia gene expression and beating

Study question How does exposure to a testosterone rich environment affect the function and gene expression of human fallopian tube epithelium (hFTE)? Summary answer Elevated testosterone level alters several gene transcripts that regulate cilia expression and negatively impacts the rate of cilia beating. What is known already The presence of estrogen in the follicular phase of the menstrual cycle increases the human fallopian tube ciliary beating frequency. The luteal phase, triggered by ovulation and increasing progesterone, is marked by a decrease in ciliary beating. Women with polycystic ovarian syndrome (PCOS) may have twice the serum level of testosterone than ovulatory women. To date, the effect of elevated androgens on the function of the human fallopian tube is not well-understood. We chose to examine the impact of elevated testosterone on hFTE. Study design, size, duration A prospective basic science study of human fallopian tube specimens from reproductive-aged women undergoing benign gynecologic surgery was performed. Fallopian tube removal at a large US academic center was collected and provided to us to continue with epithelium isolation and culturing. A total of 12 patients were analyzed in the study. Participants/materials, setting, methods Fallopian tube epithelium was isolated and exposed to two different conditions: normal with low testosterone concentration of 0.8 nM and PCOS-like, with high testosterone concentration of 2 nM. The study was conducted in both static and dynamic conditions in microfluidic devices for a total of 14 days, after which the tissue was collected for processing including RNA extraction, quantitative PCR and immunohistochemistry. After the first 7 days of each experiment, a sample of tissue from each condition was imaged to quantify cilia beating frequency. Main results and the role of chance hFTE exposed to the 2 nM testosterone displayed slower cilia beating, inhibited estrogen signaling and decreased expression of the ciliary marker FOXJ1 when compared to stimulation with 0.8 nM testosterone. Large scale data N/A. Limitations, reasons for caution The in vivo response to elevated testosterone may differ from in vitro studies. RNA amount was limited from tissue cultured in the microfluidic devices as compared to static culture. Wider implications of the findings Understanding elevated testosterone in tubal function may explain an additional contribution to subfertility in women with PCOS and other hyper-androgen disorders, aside from oligo-ovulation. Furthermore, this adds to the body of literature of fallopian tube function using a microfluidic device. Study funding/competing interest(s) NIH grants: UH3 ES029073 and R01 CA240301. There are no competing interests.

Cytologic studies of in vivo fallopian tube specimens in patients undergoing salpingo-oophorectomy.

Objectives:Recent research shows that most high grade ovarian cancer (OC) originates from the fallopian tube (FT). Cytologic evaluation of FT cells may enable early detection of OC.Material and Methods:This was a prospective study with patients enrolled from 3 centers (October 2016– August 2017). Forty-two women undergoing salpingo-oophorectomy for a pelvic mass suspicious for malignancy or undergoing risk-reducing surgery for BRCA mutations were included in the study. At the time of scheduled surgery, a novel catheter was used to collect FT cells through hysteroscopy. A pathologist blinded to surgical or pathologic findings evaluated FT cytology, and results were compared to pathology.Results:Of the 61 samples collected, 72% (44/61) met the adequacy criteria (≥5 clusters of cells with 20 cells in each cluster). Cytology classification criteria were established and applied to adequate samples. Forty-four samples were benign with mixed population of cells with round, oval, and spindled nuclei; 2-dimensional clusters; columnar cell configuration; flat sheets; cilia presence; no/mild nuclear pleomorphism; no nuclear membrane irregularities; and no nucleoli. Five samples had benign features with reactive nuclear and cytoplasmic changes and/or background inflammation, which were categorized as “reactive atypia.” Two malignant samples had features of 3-dimensional (3D) clusters, loss of mixed population of cells; increased nuclear/cytoplasmic ratio; nuclear membrane irregularity and nucleoli presence. Three samples with some but not all of malignant features were categorized as “neoplastic” (anisonucleosis; small nucleoli and features suggestive of 3D clusters). Malignant/ neoplastic samples were labeled as “Positive” (n = 5) while benign/reactive samples were labeled as “Negative” (n = 39). A high concordance rate (95%, 42/44) was observed between cytology results and histology.Conclusions:We characterized cytologic features for pathologically distinct FT samples collected in vivo using a novel catheter and demonstrated its value in detecting OC.

Exposure of human fallopian tube epithelium to elevated testosterone results in alteration of cilia gene expression and beating

How does exposure to a testosterone rich environment affect the function and gene expression of human fallopian tube epithelium (hFTE)? Elevated testosterone level alters several gene transcripts that regulate cilia expression and negatively impacts the rate of cilia beating. The presence of estrogen in the follicular phase of the menstrual cycle increases the human fallopian tube ciliary beating frequency. The luteal phase, triggered by ovulation and increasing progesterone, is marked by a decrease in ciliary beating. Women with polycystic ovarian syndrome (PCOS) may have twice the serum level of testosterone than ovulatory women. To date, the effect of elevated androgens on the function of the human fallopian tube is not well-understood. We chose to examine the impact of elevated testosterone on hFTE. A prospective basic science study of human fallopian tube specimens from reproductive-aged women undergoing benign gynecologic surgery was performed. Fallopian tube removal at a large US academic center was collected and provided to us to continue with epithelium isolation and culturing. A total of 12 patients were analyzed in the study. Fallopian tube epithelium was isolated and exposed to two different conditions: normal with low testosterone concentration of 0.8 nM and PCOS-like, with high testosterone concentration of 2 nM. The study was conducted in both static and dynamic conditions in microfluidic devices for a total of 14 days, after which the tissue was collected for processing including RNA extraction, quantitative PCR and immunohistochemistry. After the first 7 days of each experiment, a sample of tissue from each condition was imaged to quantify cilia beating frequency. hFTE exposed to the 2 nM testosterone displayed slower cilia beating, inhibited estrogen signaling and decreased expression of the ciliary marker FOXJ1 when compared to stimulation with 0.8 nM testosterone. N/A. The in vivo response to elevated testosterone may differ from in vitro studies. RNA amount was limited from tissue cultured in the microfluidic devices as compared to static culture. Understanding elevated testosterone in tubal function may explain an additional contribution to subfertility in women with PCOS and other hyper-androgen disorders, aside from oligo-ovulation. Furthermore, this adds to the body of literature of fallopian tube function using a microfluidic device. NIH grants: UH3 ES029073 and R01 CA240301. There are no competing interests.

Grossing Issues in Ovarian and Fallopian Tube Pathology

Abstract Ovaries and fallopian tubes are often removed for treatment of various benign and malignant gynecological conditions including prophylactic resections in high-risk patients. Meticulous grossing techniques are essential for staging, prognostication, and accurate diagnosis. We conducted a comprehensive review of published literature on methods for grossing pelvic adnexal specimens, including standard textbooks and grossing manuals, supplemented by a limited review of grossing protocols from academic institutions. This review addresses common issues encountered during the grossing of ovarian and fallopian tube specimens.

Abstract B15: BRCA haploinsufficiency promotes gluconeogenesis in fallopian tube epithelial cells

Abstract Introduction: High-grade serous ovarian cancer (HGSC) is one of the deadliest gynecologic malignancies due to presentation at advanced stages and the development of chemotherapy resistance. The recent discovery that HGSC arises from fallopian tube epithelia (FTE) and the analysis results obtained from TCGA study are helping in understanding the genes involved in the progression of the disease. HGSC is genetically unstable due to the loss of function mutations in BRCA1, BRCA2, PALB2, ATM, and RAD51 genes involved in DNA damage response. These genes also regulate cellular metabolism, antioxidant, and detoxification responses. Preliminary data show that phase II antioxidant enzymes are significantly reduced in HGSC and there is an increase in reactive oxygen species (ROS) in cells harboring p53 and BRCA1 mutations in precursor lesions of FTE and HGSC. We also observed differential mRNA expression of PCK1 and PCK2, GLUT1 genes involved in gluconeogenesis and glycolysis. Mitochondria are one of the major organelles for the production of ROS, and it is a well-known fact that metabolism is drastically changed in cancer cells compared to normal cells. Our aim was to determine the metabolic and fuel dependency in preneoplastic transformed cells, characterize the mitochondrial phenotype, and link these dependencies to transformation in FTE. Methods: Fallopian tube specimens were obtained from the Biospecimen Shared Resources Core at SCCC. Patients undergoing risk reduction surgery were consent and FTE cells were obtained from BRCA and non-BRCA. Preneoplastic cell lines were then generated by hTERT, p53 mutation (R175H), and HPVE7. To mimic the genetic changes of in vivo HGSC, oncogenes CCNE1 and PIK3CA-H1047R were then overexpressed (OE) in these immortalized cell lines. Xenografts were generated from the transformed FTE cells lines. Agilent Seahorse assays were used to study the fuel dependency, oxidative phosphorylation, and glycolysis. Results: FTE-BRCA1 and FTE-BRCA2 cells showed differences in both glycolytic and oxidative metabolism depending on the oncogenic type. The transformed cells had lower oxidative metabolism and there was also discrepancy in the dependency of metabolites utilized by these cell lines for energy. As seen by mRNA, FTE-BRCA cells had more PCK2 protein and were characterized by higher metabolic rates; these observations were augmented in the presence of PIK3CA-H1047R. However, these FTE preneoplastic and oncogene transformed cells showed no difference in their mitochondrial mass or membrane potential. Conclusion: FTE-BRCA mutant cells utilize glycolysis or gluconeogenesis pathways to overcome metabolic stress depending on which oncogene is driving carcinogenesis. Further work is required to elucidate the mechanism of PCK2 and BRCA link in ovarian cancer carcinogenesis. Citation Format: Iru Paudel, Ramlogan Sowamber, Leah Dodds, Alex Sanchez, Marilyn Huang, Matthew Schlumbrecht, Brian Slomovitz, Sophia George. BRCA haploinsufficiency promotes gluconeogenesis in fallopian tube epithelial cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B15.

Histopathological study of surgically resected specimens of fallopian tube

Background: Fallopian Tubes are very common surgical specimen received in the pathological laboratory. It is affected by wide spectrum of both non neoplastic and neoplastic lesions. But there is very few studies described the frequency of various histopathological spectrums of lesions of fallopian tube. Aims & Objectives: To study the various histopathological lesions seen in surgically resected specimens of fallopian tube and their age distributions.Material and Method: A total of 200 surgically resected specimen of fallopian tube of all age group of patients which are received for one and half year duration, are processed with routine histopathological techniques. Histopathological features were studied on Haematoxylin and Eosin stain.Results: In our studies majority of the cases are belongs to 40 to 60 years of age out of 200 specimens. In this study, most of the patients were undergone total abdominal hysterectomy with salpingo-oophorectomy (60%). In our study out of 200 cases 63 (31.50%) specimens show unremarkable histology. Only 1(0.50%) case shows neoplastic pathology. Most common histopathological findings observed are paratubal cyst, ectopic tubal gestation and Walthard Cell Nests.Conclusion: Present study shows broad spectrum of pathological lesions in fallopian tube. Majority of the lesions are non neoplastic in nature. Thorough histopathological examination of fallopian tube specimens is necessary to document many lesions including rare primary intraepithelial malignancy which can be missed clinically and found incidentally on histopathological examination.

Detection and genotyping of CMV and HPV in tumors and fallopian tubes from epithelial ovarian cancer patients

Viral and bacterial infections are detected in epithelial ovarian cancer (EOC) tissues. Since the fallopian tubes are often affected by pelvic inflammatory disease (PID) and the majority of serous EOCs appear to originate from dysplastic lesions in the distal tube, it is relevant to consider the potential role that infectious agents may play in ovarian carcinogenesis. We sought to analyze the prevalence of human papillomavirus (HPV) and cytomegalovirus (CMV) in EOC tissue and fallopian tube specimens obtained at tumor resection. Ovarian cancer and fallopian tube tissue samples obtained from patients with EOC were analyzed by both qualitative and quantitative PCR to detect and quantify viral DNA. The presence of CMV and HPV DNA was detected in 70% and 74% cancerous ovarian tissues, respectively, and was significantly higher in EOC than in benign tumor cases (P ≤ 0.01). CMV or HPV infection was observed also in the fallopian tube samples. Infection with HPV16 was determined in 70% of EOC cases. Almost two thirds of EOC patients demonstrated coinfection with CMV and HPV in the pathological samples. The results revealed that the presence of CMV and HPV in EOC samples is common. CMV and HPV infections can be potential risks for EOC development.

Abstract DP-005: RNA-SEQUENCING OF FALLOPIAN TUBE – FIMBRIA AND HGSC FROM BRCA MUTATION CARRIERS

Abstract Inheritance of a deleterious mutation in the BRCA1/2 genes increases the risk of the disease by up to 40%. The origin of the disease is still debated; however considerable evidence suggests the fallopian tube as the primary site of disease origin. The fallopian tube epithelium changes morphologically and genomically with the ovulatory cycle. To further understand the transcriptomic profile of the fallopian tube epithelium amongst patients with and without a BRCA mutation who have undergone prophylactic surgery, samples with clinically annotated ovulatory cycle status were analyzed by next-generation sequencing (RNA-Seq). The results from this study will provide an understanding of the origins of the disease and how new therapeutic and preventative interventions can be applied early in the development of the disease. METHODS: In total a cohort of 68 archival formalin fixed paraffin embedded (FFPE) fallopian tube -fimbria was amassed: FTE-BRCA1 (n=32), FTE-BRCA2 (n=4), chemonaive HGSC-BRCA1 (n=9), FTE-nonBRCA (n=26). The pre-menopausal fallopian tube specimens were sub-divided by ovulatory cycle: normal-Follicular, normal-Luteal, BRCA-Follicular, BRCA-Luteal. The majority of the FTE specimen were obtained from pre-menopausal women (post-menopausal n=2). Laser capture microdissection was performed on the distal end of the fallopian tubes – the fimbria. Six-twelve, 10um FFPE sections were cut and stained with hematoxylin prior to LCM. RNA was extracted using the Roche High Pure FFPE Micro Kit and samples were processed using Illumina Tru-Seq Stranded Total RNA Kit with RiboGold ready and sequenced on the Illumina Hi-seq 2000 V3. Raw results, in FASTQ format, were then processed through the RNA sequencing pipeline to generate results including gene expression data. RESULTS: Gene expression differences between carriers and non-carriers (FTE-BRCA1/2 and FTE-nonBRCA) revealed genes involved in metabolic pathways namely: oxidative phosphorylation, mitochondrial functions, glycolysis/gluconeogenesis and glycan biosynthesis and metabolism: UGT2A1, ST6GALNNAC6, Complex 1 (ND1, ND2, ND4, NDL4, ND5), ATP6/ATP8, and COX1-3. A comparison between the tumor and fimbria cases showed increased activity in the HMGBI Signaling (increase in HAT1, KAT2B, LIF, JAK3 and PIK3CA and decrease in RAP1A/B, ATM and HMGB1). CONCLUSION: These results highlight BRCA1/2 distinct unique preneoplastic processes not previously identified. The fallopian tube epithelial in the fimbria in BRCA1 and BRCA2 mutation carriers have increased metabolic activity, indicated by their gene expression profiles. HGSC developed BRCA1 germline mutation carriers have an increased histone acetyltransferase activity shown to be involved in BRCA mediated DNA damage repair. Further analysis is required to understand how the ovulatory cycle influences the fallopian tube epithelium transcriptome, but preliminary results suggest that pathways altered include: metabolic pathways, apoptosis pathways, p53 pathways and mismatch repair pathways. These results support previous findings in addition to providing new insight into the early development of the disease. Citation Format: Ramlogan Sowamber, Leah Dodds, Anca Milea, Iru Paudel, Michael Considine, Leslie Cope, Patricia A Shaw and Sophia HL George. RNA-SEQUENCING OF FALLOPIAN TUBE – FIMBRIA AND HGSC FROM BRCA MUTATION CARRIERS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-005.

Optical Resolution Photoacoustic Microscopy of Ovary and Fallopian Tube

Ovarian cancer is the leading cause of death among gynecological cancers, but is poorly amenable to preoperative diagnosis. In this study, we investigate the feasibility of “optical biopsy,” using high-optical-resolution photoacoustic microscopy (OR-PAM) to quantify the microvasculature of ovarian and fallopian tube tissue. The technique is demonstrated using excised human ovary and fallopian tube specimens imaged immediately after surgery. Quantitative parameters are derived using Amira software. The parameters include three-dimensional vascular segment count, total volume and length, which are associated with tumor angiogenesis. Qualitative results of OR-PAM demonstrate that malignant ovarian tissue has larger and more tortuous blood vessels as well as smaller vessels of different sizes, while benign and normal ovarian tissue has smaller vessels of uniform size. Quantitative analysis shows that malignant ovaries have greater tumor vessel volume, length and number of segments, as compared with benign and normal ovaries. The vascular pattern of benign fallopian tube is different than that of benign ovarian tissue. Our initial results demonstrate the potential of OR-PAM as an imaging tool for fast assessment of ovarian tissue and fallopian tube and could avoid unnecessary surgery if the risk of the examined ovary is extremely low.