Tumor Of Genital Tract Research Articles

Indications regarding early detection screening for genital tract neoplasms

Testicular tumors and penile cancer are rare but potentially life-threatening diseases. Testicular tumors primarily affect younger men, while penile cancer is more common in older men. Early detection can significantly improve survival rates. This article investigates the indications for early detection screenings for testicular tumors and penile cancer. Acomprehensive literature review was conducted to analyze current studies and guidelines. No general screening programs are recommended for either type of cancer. For testicular tumors, self-examination of the testes is recommended, while for penile carcinomas, education on risk factors such as human papillomavirus (HPV) infections or phimosis is emphasized. In both cases, medical examination is crucial. Education and awareness, especially among at-risk groups, are essential. Physicians play akey role in conducting and recommending early detection measures.

Advanced Malignant Melanoma of the Vulva in a 70 years old woman

Vulvar melanoma is a rare malignant tumor of the female genital tract tend to occur in older age women and a high tendency to metastasize because the diagnosis is usually delayed (1). In this case report, we present a 70-year-old para 8 woman who presented with progressively increasing vulvar swelling of 2 years and multiple visit to health institution. Examination revealed 7cm diameter multi-nodular mass with areas of dark and dark blue-violet color filling the introitus that involves the clitoris, labia minora, lower third of the anterior vagina and urethra. Incisional biopsy from the mass showed malignant melanoma. Imaging with CT scan revealed bilateral lung metastasis. Palliative chemotherapy was planned but the patient lost to follow up.

Unexpected early pregnancy during myomectomy followed by successful term delivery: A case report.

Leiomyoma, also known as uterine fibroid, is a non-malignant tumor originating from the uterus's smooth muscles. It is the most common benign tumor in the female genital tract, exhibiting varying size and form that can distort the uterus's shape. Uterine fibroids affect 2.7-10.7% of pregnant women and can lead to increased risks during pregnancy, such as miscarriage, placental abruption, preterm labor, and fetal malpresentation. Myomectomy is a surgical intervention for uterine fibroids, but it has drawbacks, including hemorrhage, fever, infection, ureter ligation, adhesive disorders, and unplanned hysterectomy. In this case report, we present a 32-yr-old woman with a large leiomyoma who underwent laparotomy myomectomy due to abdominal pain and heavy menstrual bleeding. 4 wk after the myomectomy, she was referred to the Obstetric Clinic of Ayatollah Taleghani hospital, Tehran, Iran complaining of delayed menstruation. Her beta-human chorionic gonadotropin test was positive. Ultrasound revealed a fetus with an estimated gestational age of 6 wk and 4 days. The pregnancy continued with no complications. At 38 wk of gestation, she underwent a cesarean section and delivered a healthy newborn. This case report supports previous publications that have demonstrated the safety of myomectomy during pregnancy.

Synchronous Endometrial and Ovarian Cancers: One Case Report

Synchronous ovarian and endometrial cancer (SEOC) is a rare instance butit accounts for 50–70% of all synchronous female genital tract tumors We report a case of a woman that was diagnosed with SEOC and underwent surgical staging. Patients with synchronous cancers have better prognosis than those with single disseminated cancer. Their detection in a relatively early stage suggests diagnosis may be facilitated by early symptoms from the endometrial carcinoma, and that these lesions are biologically of relatively low grade. The first symptoms reported by our patients and the course of the disease were concordant with data from the literature.

Capillary Haemangioma of Fallopian Tube: Usual Tumor at Unusual Site

Fallopian tube neoplasms are uncommon, accounting to approximately 1-2% of all female genital tract neoplasms. Hemangiomas are the most common soft tissue neoplasms. We present an unusual case of capillary hemangioma of fallopian tube which was incidentally detected in a patient who underwent abdominal hysterectomy with salphingo-oophorectomy.

Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix.

Small cell cervical carcinoma (SCCC) is the most common neuroendocrine tumor in the female genital tract, with an unfavorable prognosis and lacking an evidence-based therapeutic approach. Until now, the distinct subtypes and immune characteristics of SCCC combined with genome and transcriptome have not been described. We performed genomic (n = 18), HPV integration (n = 18), and transcriptomic sequencing (n = 19) of SCCC samples. We assessed differences in immune characteristics between SCCC and conventional cervical cancer, and other small cell neuroendocrine carcinomas, through bioinformatics analysis and immunohistochemical assays. We stratified SCCC patients through non-negative matrix factorization and described the characteristics of these distinct types. We further validated it using multiplex immunofluorescence (n = 77) and investigated its clinical prognostic effect. We confirmed a high frequency of PIK3CA and TP53 alterations and HPV18 integrations in SCCC. SCCC and other small cell carcinoma had similar expression signatures and immune cell infiltration patterns. Comparing patients with SCCC to those with conventional cervical cancer, the former presented immune excluded or 'desert' infiltration. The number of CD8+ cells in the invasion margin of SCCC patients predicted favorable clinical outcomes. We identified three transcriptome subtypes: an inflamed phenotype with high-level expression of genes related to the MHC-II complex (CD74) and IFN-α/β (SCCC-I), and two neuroendocrine subtypes with high-level expression of ASCL1 or NEUROD1, respectively. Combined with multiple technologies, we found that the neuroendocrine groups had more TP53 mutations and SCCC-I had more PIK3CA mutations. Multiplex immunofluorescence validated these subtypes and SCCC-I was an independent prognostic factor of overall survival. These results provide insights into SCCC tumor heterogeneity and potential therapies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report

BackgroundThe risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids.Case presentationThis study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge.ConclusionsWhen observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.

Exploring the histogenesis of STK11 adnexal tumour using electron microscopy

STK11 adnexal tumour is a recently described female genital tract tumour, usually identified in a paratubal location, often associated with Peutz-Jeghers syndrome (PJS) and with STK11 gene alterations identified in most of the cases. Morphologically, this tumour is composed of cells arranged in a variety of patterns, including cords, trabeculae, tubules and cystic and acinar structures. The cells are only moderately pleomorphic and mitotic activity is variable. As tumour cells express epithelial, sex cord stromal and mesothelial markers, STK11 adnexal tumour may be of sex cord stromal, epithelial or mesothelial origin; a Wolffian origin has also been suggested. We report the ultrastructural features of two STK11 adnexal tumours and compare their ultrastructural features with those of other sex cord stromal tumours, a granulosa cell tumour cell line, as well as the known ultrastructural features of epithelial, mesothelial and Wolffian cells. On ultrastructural examination, two STK11 adnexal tumours showed an admixture of elongated cells with regular elongated nuclei and polygonal cells with nuclei showing markedly irregular outlines and prominent nucleoli. Extracellular collagen fibres were identified. These are common ultrastructural features of sex cord stromal tumours, principally sex cord tumour with annular tubules; no ultrastructural features of epithelial, mesothelial or Wolffian cells were found. These findings in conjunction with the shared clinical and genetic association with PJS and shared molecular changes in STK11 gene suggest that STK11 adnexal tumour represents a poorly differentiated sex cord tumour.

High-Grade Serous Ovarian Cancer-A Risk Factor Puzzle and Screening Fugitive.

High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients (BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy. Therefore, there is an urgent need to identify the substantial risk factors for both predisposed and low-risk populations of women, as well as to create an economically and clinically justified screening program. This paper reviews the classic and novel risk factors for HGSOC and methods of diagnosis and prediction, including serum biomarkers, the liquid biopsy of circulating tumor cells or circulating tumor DNA, epigenetic markers, exosomes, and genomic and proteomic biomarkers. The novel future complex approach to ovarian cancer diagnosis should be devised based on these findings, and the general outcome of such an approach is proposed and discussed in the paper.

MR Imaging Findings of Uterine Adenomatoid Tumors.

Adenomatoid tumor is a rare benign genital tract neoplasm of mesothelial origin. Uterine adenomatoid tumors occur in the outer myometrium and may mimic leiomyomas. Because hormonal treatment is not applicable to adenomatoid tumors and laparoscopic enucleation is not easy as myomectomy, it is important to differentiate adenomatoid tumors from leiomyomas for the adequate treatment. The purpose of this study is to evaluate the MRI findings of adenomatoid tumor for the differentiation from leiomyoma. MRI findings of surgically proven 10 uterine adenomatoid tumors in 9 women were retrospectively evaluated with correlation to histopathological findings. All 10 tumors appeared as solid myometrial masses and showed heterogeneous signal intensity with admixture of partially ill-defined slight high-intensity areas containing abundant tubular tumor cells and well-defined myoma-like low-intensity areas reflecting smooth muscle hypertrophy on T2WI including 4 lesions with peripheral ring-like high intensity. High-intensity areas on T2WI tended to show high intensity on diffusion-weighted imaging (DWI) with relatively high apparent diffusion coefficient (ADC), suggesting T2 shine-through effect due to abundant tubules. Intra-tumoral hemorrhage revealed on MRI was rare. Early intense contrast-enhanced areas on dynamic contrast-enhanced study were observed dominantly within the high-intensity areas but rarely within the low-intensity areas on T2WI. The outer myometrial mass with the admixture of well-defined low- and ill-defined high-intensity areas on T2WI may be suggestive of adenomatoid tumor. Peripheral ring-like high intensity on T2WI and DWI may also be suggestive. Dynamic contrast-enhanced MR study may be helpful for the differentiation from leiomyoma.

Methylation of the Selected TP53 Introns in Advanced-Stage Ovarian Carcinomas.

Objective: Advanced-stage ovarian cancer (OC) is among the most fatal female genital tract neoplasms worldwide. Although different genetic mechanisms have been shown to be involved in ovarian carcinogenesis, the role of TP53 introns methylation is still unresolved. We performed methylation analysis of introns 1, 3, and 4 of the TP53 to identify patterns in primary stage III OCs, corresponding metastases, and healthy tissues. Methods: The study involved samples of paraffin-embedded tissues obtained from 80 patients with stage III OCs, who underwent surgery at the Department of Gynecology and Gynecologic Oncology of the Military Institute of Medicine in Warsaw, Poland. Altogether, 40 serous-type G2/3 OCs and 40 endometrioid-type G2/3 OCs were included. From the same patient, metastatic and normal tissues were simultaneously analyzed. As a control group, 80 tissue samples were collected from patients after bariatric operations. Human ovarian cancer A2780 cell line was also investigated. Total genomic DNA was isolated from paraffin-embedded tissue blocks and the methylation analysis was performed by bisulfite DNA conversion, DNA amplification with specific primers, cloning, and DNA sequencing. Results: All of the samples of intron 1 of TP53 were un-methylated in OCs, metastatic tissues, and in healthy tissues from the same patient. Also, no methylation of TP53 intron 1 was detected in cells from the human A2780 ovarian cancer cell line and in all samples from control group. In all samples, introns 3 and 4 of the TP53 were methylated in primary tumors, metastatic tissue, and in healthy tissue from the same patient, in human A2780 ovarian cell line, and in DNA samples from healthy patients. None of the clinicopatholocal features was related to the TP53 introns methylation status. Conclusions: Our data on TP53 introns methylation sheds new light on the mechanism of p53 activity for a better understanding of cancer biology. The study suggests the existence of an additional regulation rule of TP53 activity that involves demethylation-methylation mechanisms. Methylation at introns 3 and 4 may also overall help in protecting TP53 against damage by viral restrictases or viral DNA integration.

Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer-The Possibility or the Necessity?

High-grade serous tubo-ovarian cancer (HGSTOC) is the most lethal tumor of the female genital tract. The foregoing therapy consists of cytoreduction followed by standard platinum/taxane chemotherapy; alternatively, for primary unresectable tumors, neo-adjuvant platinum/taxane chemotherapy followed by delayed interval cytoreduction. In patients with suboptimal surgery or advanced disease, different forms of targeted therapy have been accepted or tested in clinical trials. Studies on HGSTOC discovered its genetic and proteomic heterogeneity, epigenetic regulation, and the role of the tumor microenvironment. These findings turned attention to the fact that there are several distinct primary tumor subtypes of HGSTOC and the unique biology of primary, metastatic, and recurrent tumors may result in a differential drug response. This results in both chemo-refractoriness of some primary tumors and, what is significantly more frequent and destructive, secondary chemo-resistance of metastatic and recurrent HGSTOC tumors. Treatment possibilities for platinum-resistant disease include several chemotherapeutics with moderate activity and different targeted drugs with difficult tolerable effects. Therefore, the question appears as to why different subtypes of ovarian cancer are predominantly treated based on the same therapeutic schemes and not in an individualized way, adjusted to the biology of a specific tumor subtype and temporal moment of the disease. The paper reviews the genomic, mutational, and epigenetic signatures of HGSTOC subtypes and the tumor microenvironment. The clinical trials on personalized therapy and the overall results of a new, comprehensive approach to personalized therapy for ovarian cancer have been presented and discussed.

Extensive Vulvectomy and Reconstructive Flaps for Advanced Vulvar Cancer in Young Woman: Case Reports

Introduction: : Vulvar cancer is a rare disease accounting for approximately 5% of female genital tract tumors worldwide. It is a squamous cell cancer that mostly affects older women over the age of 65. In the existing body of literature, no instances of vulvar cancer have been documented in the form of case reports. Therefore, this study aimed to report the challenges and outcomes of vulvectomy with reconstructive flap in vulvar cancer survivors in a 39-year-old woman. Case Presentation: A 39-year-old woman with a palpable lump around the vulva was present and being examined. The anatomic pathology report (APR) features suggested poorly differentiated malignant tumors. A neoadjuvant chemotherapy was then administered to the patient aimed at shrinking the size of the tumor. However, there was no effective response to the chemotherapy, which resulted in a progressive tumor. Extensive vulvectomy and reconstructive flap were carried out to support quality of life, and the outcomes were reported, including flap, survival, complications, and mortality. These outcomes were evaluated between November 2021 and March 2023. No total flap loss was observed, and neither was there any donor site morbidity or mortality during the process. Conclusions: This study showed that vulvar cancer was a rare condition at a young age. Advanced vulvar cancer was found in the patients and extensive vulvectomy surgery was carried out followed by a pedicled ALT flap. This option was currently the best for immediate reconstruction due to the preservation of sensibility and tissue availability in the donor areas. The result showed no wound dehiscence, marginal necrosis, or surgical site infection. After 15 months of follow-up, the flap was observed to have good vascularization. The association of the Gynecologist with the Plastic Surgeon offered palliative care to improve the quality of life of the patient and provide good postoperative results.

Serous Papillary Adenofibroma of Fallopian Tube in a Case of Endometrial Adenocarcinoma: A Rare Case Report

Introduction: Primary fallopian tube neoplasms are usually rare, and they are the rarest of all female genital tract neoplasms. According to the WHO classification, papillomas, adenofibroma, cystadenoma, cystadenofibroma, and metaplastic papillary tumors belong to the group of benign tumor masses that arise from the fallopian tubes. Methods: In our case, during an abdominal hysterectomy in a 45-yearold woman suspicious of endometrial adenocarcinoma, a right tubal mass was incidentally found. Results: Microscopic findings revealed features of serous papillary adenofibroma. Serous papillary adenofibroma is a very rare tumor. Till date, only a few cases have been reported worldwide, more so in the presence of endometrial malignancy. Conclusion: Serous papillary adenofibroma is often an incidental finding; thus, it is important to gross the specimen minutely to look for any such finding in the adnexa to avoid missing out on such rare neoplasm.

Uterine Neurotrophic Tyrosine Receptor Kinase Rearranged Spindle Cell Neoplasms: Three Cases of an Emerging Entity.

Uterine sarcomas are rare; most are either smooth muscle or endometrial stromal in origin. Recent molecular advances have identified several, genetically defined entities with specific morphologic, clinicopathological associations, and therapeutic options. We report 3 cases of uterine neurotrophic tyrosine receptor kinase ( NTRK )-rearranged spindle cell neoplasms," currently classified as "emerging entities" in the WHO Classification of Female Genital Tract Tumors, 2020, Fifth Edition. The affected patients were 32, 34, and 42 years of age. Two patients presented with vaginal bleeding; the third presented with a cervical mass found incidentally during laparoscopy for an ectopic gestation. All 3 tumors were polypoid masses that distorted the cervix. Microscopically, they comprised cellular, fascicular, and storiform, plump spindle cells, with occasional rounded cells, and frequent mitoses (4-48/10 high power fields) in a myxoid stroma. All 3 cases showed entrapment of benign cervical glands. Inflammatory cell infiltrates, including plasma cells, were noted in all 3 tumors. One case had tumor cell necrosis, osteoid-like material, and osteoclast-like giant cells and showed lymphovascular invasion. Immunohistochemically, our cases showed patchy S100 (2/3) and CD34 (3/3) positivity. CD10 was positive in 2/3 cases. 3/3 cases showed pan-tropomyosin receptor kinase positivity (cytoplasmic). The NTRK -translocations demonstrated were: NTRK1::TMP3, NTRK1::TPR, and NTRK3::SPECC1L . Two of the patients had extensive disease and underwent chemotherapy. Larotrectinib was approved for one patient who demonstrated a striking reduction in tumor volume upon initiation of this treatment.

Sarcoma estromal endometrial extrauterino primario de bajo grado

Endometriosis is a common benign lesion whose importance lies in the associated symptomatology and the possibility of malignant transformation. Endometrial stromal sarcoma is a rare tumor, accounting for only 0.2% of all female genital tract tumors. Primary extrauterine endometrial stromal sarcomas are even rarer, are frequently associated with endometriosis, and have been reported in the ovaries, fallopian tubes, pelvic cavity, abdominal cavity, and retroperitoneum in the absence of uterine pathology. We describe a case of a female patient who consulted for dysmenorrhea, dysuria, and dyschezia. Pelvic magnetic resonance showed a heterogeneous tumor in the left adnexa compatible with endometrioma. Histopathological findings and immunohistochemical staining were consistent with the diagnosis of primary low-grade extrauterine endometrial stromal sarcoma. The patient underwent total hysterectomy, bilateral oophorosalpingectomy, total omentectomy, and pelvic and para-aortic lymph node resection.

Evaluation of Accuracy of Intraoperative Frozen Section and Imprint Cytology in Gynecological Neoplasms-A Descriptive Cross-Sectional Study of 50 Cases in Tertiary Care Center.

Aims and Objectives Gynecological neoplasms are among the most common cancers in female population of India and worldwide. Various new advances have been made to diagnose gynecological pathologies which include imprint cytology and frozen sections in addition to the histopathological techniques. The aim of the study was to assess the diagnostic accuracy of intraoperative diagnostic procedure with gold standard histopathology. Method The study included 50 patients who had suspected gynecological neoplasm in a time period of 12 months. Their intraoperative diagnosis was made on frozen section and imprint cytology to rule out benign or malignant lesions and compared with gold standard histopathology. Results Our study concludes that maximum cases of female genital tract neoplasms belonged to the age group of 19 to 76 years, with 60% cases in postmenopausal age group. Overall diagnosis of 62, 52, and 76% malignancies were made on imprint cytology, frozen section, and histopathological examination, respectively. Conclusion The study concludes that diagnostic accuracy by intraoperative imprint cytology is higher (80%) than frozen section (76%). True positive cases were maximally reported by histopathology. True negative and false positive cases were equally reported by both frozen and imprint cytology. False negative cases were reported by frozen section more than by imprint cytology. The kappa statistical value was lesser in frozen versus histopathology and more in imprint versus histopathology. The sensitivity, specificity, positive predictive value, and negative predictive value for imprint cytology were 77.5, 90.0, 96.9, and 50%, respectively, whereas for frozen section, it was 72.5, 90.0, 96.7, and 45.0%, respectively.

The Role of Peroxisome Proliferator-Activated Receptors in Endometrial Cancer.

Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins which regulate gene expression. In order to investigate the role of PPARs in endometrial cancer, we conducted a literature review using the MEDLINE and LIVIVO databases and were able to identify 27 relevant studies published between 2000 and 2023. The PPARα and PPARβ/δ isoforms seemed to be upregulated, whereas PPARγ levels were reported to be significantly lower in endometrial cancer cells. Interestingly, PPAR agonists were found to represent potent anti-cancer therapeutic alternatives. In conclusion, PPARs seem to play a significant role in endometrial cancer.

Abstract 5554: Mammaglobin-A expression in highly specific for tumors derived from the breast, the female genital tract and salivary gland tumors

Abstract Background: Human mammaglobin-A (SCGB2A2) is a small epithelial secretory protein with unknown function. Because of its frequent expression in breast epithelial cells, it is used as a diagnostic marker for breast cancer and represents an attractive target for novel therapies involving adaptive T cell transfer and antitumor vaccines for breast cancer patients. However, there is growing evidence that mammaglobin-A expression is not limited to breast cancers. Methods: In order to comprehensively determine mammaglobin-A expression in normal and neoplastic tissues, a tissue microarray containing 16,328 samples from 128 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: Mammaglobin-A positivity was found in 37 of 128 tumor categories, 32 of which were derived of one of four organs: breast (6 tumor categories), endometrium (5 tumor categories), ovary (5 tumor categories), and salivary glands (16 tumor categories). Only 5 additional tumor types showed occasional mammaglobin positivity. These tumors mostly exhibited a weak mammaglobin-A staining and included medullary thyroid cancer, teratoma of the testis, squamous cell carcinoma of skin and the pharynx, and prostatic adenocarcinoma (Gleason 5+5=10). Among 1,139 evaluable invasive breast carcinomas of no special type (NST), low mammaglobin-A immunostaining was linked to high BRE grade (p=0.0011), a loss of estrogen and progesterone receptor expression (p<0.0001 each), and triple negative status (p<0.0001) but not to patient survival. In endometrial cancer, low mammaglobin-A immunostaining was linked to advanced tumor stage (p=0.0198). Although a similar trend was seen for endometrioid and serous high-grade carcinomas of the ovary, these associations did not reach statistical significance. Conclusions: Our data characterize mammaglobin-A as a highly specific marker for tumors derived from either female organs or the salivary gland. The potential use of anti-Mammaglobin therapies should be studied also in other mammaglobin-positive tumor types. Citation Format: Natalia Gorbokon, Patrick Timm, David Dum, Anne Menz, Franziska Büscheck, Cosima Völkel, Andrea Hinsch, Maximilian Lennartz, Andreas Luebke, Claudia Hube-Magg, Christoph Fraune, Christian Bernreuther, Patrick Lebok, Till Clauditz, Frank Jacobsen, Guido Sauter, Ria Uhlig, Stefan Steurer, Sarah Minner, Andreas Marx, Ronald Simon, Eike Burandt, Till Krech. Mammaglobin-A expression in highly specific for tumors derived from the breast, the female genital tract and salivary gland tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5554.

Immunothrombosis in cancer patients: contribution of neutrophil extracellular traps, ADAMTS-13 and von Willebrand factor

Introduction. Neutrophil extracellular traps (NETs) and von Willebrand factor (vWF) are integral players in thrombosis and inflammation in cancer patients. It has been increasingly evident that an active interplay exists between NETs and vWF. Some studies suggest that NETs cause decrease in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity, being an arm in the pathogenesis of both thrombotic microangiopathies (TMA) and other thrombotic complications during oncological process.Aim: to assess a crosstalk between NETs, vWF, and ADAMTS-13 in uterine, ovarian, breast malignant neoplasms as well as cervical canal adenocarcinoma.Materials and Methods. From September 2019 to July 2022, a prospective controlled interventional non-randomized study was carried out with 106 patients hospitalized for planned surgical treatment aged 30 to 72 years. The main group included 73 patients with malignant neoplasms of the female genital organs and mammary glands, stage I–III: uterine cancer (subgroup 1; n = 18), ovarian cancer (subgroup 2; n = 21), cervical cancer – adenocarcinoma of cervical canal (subgroup 3; n = 9) and breast cancer (subgroup 4; n = 25). The control group consisted of 33 women with female genital tract and breast benign neoplasms. In all patients, serum levels of vWF, citrullinated histone H3 (citH3), MPO (myeloperoxidase) antigen, ADAMTS-13 activity, ADAMTS-13 antigen, and D-dimer were evaluated.Results. The study revealed significant differences in the concentration of NETosis markers between the main and control groups. Patients with uterine cancer and adenocarcinoma of the cervical canal peaked at NETosis markers. At the same time, there were significant differences in citH3 concentration among patients with «early» (stage I) and «not early» (stage II–III) disease forms. While assessing level of von Willebrand factor (vWF:Ag), antigen (ADAMTS-13:Ag), and ADAMTS-13 activity (ADAMTS-13:Ac), significant differences were found between the main and control groups (p < 0.0001). The vWF in the main groups was sharply increasedwhereas ADAMTS-13 antigen concentration and activity were decreased. A сorrelation analysis among oncological patients in main group showed that while citH3 level increased, it was also paralleled with rise in vWF:Ag (ρ = 0.80; p < 0.01) and MPO:Ag (ρ = 0.87; p < 0.01); increase in MPO:Ag level was coupled to rise in vWF:Ag (ρ = 0.70; p< 0.01), but increase in vWF:Ag occurred along with decline in ADAMTS-13:Ac (ρ = –0.43; p < 0.01) and ADAMTS-13:Ag (ρ= –0.42; p < 0.01).Conclusion. The interplay between NET, vWF, and ADAMTS-13 leads to a vicious circle, reduces ADAMTS-13 activity by increasing serum vWF concentration, which positively correlates with severity and mortality in TMA, acute ischemic infarction, and COVID-19. Targeting the NETs-vWF axis may pave the way for therapeutic strategies for immunothrombosis in various diseases, including cancer.