Mucinous Ovarian Carcinoma Research Articles

Infiltrative versus expansile invasion: Clinical correlates in mucinous ovarian carcinoma

Infiltrative versus expansile invasion: Clinical correlates in mucinous ovarian carcinoma

TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas

TP53 and KRAS co-mutations are associated with worse outcomes in mucinous ovarian carcinomas

Evaluation of Selected MRI Parameters in the Differentiation of Mucinous Ovarian Carcinomas and Metastatic Ovarian Tumors

Introduction: Analysis of selected MRI parameters in initial MRI for the characterization of ovarian masses enables differentiation between mucinous ovarian carcinoma and metastatic ovarian tumors. Material and Methods: A prospective analysis of contrast-enhanced MRI of patients with suspected ovarian masses diagnosed in ultrasound and CT examination. Morphological criteria, such as the size of lesion, bilateral location, presence of “mille-feuille sign”, so-called Seidman criteria, as well as the diffusion weighted imaging and dynamic contrast enhancement of each lesion, were evaluated. Patients were allocated into two groups; the first group contained patients with mucinous ovarian cancer, and the second group contained patients with metastatic ovarian tumors. Results: A total of 35 patients were enrolled into the study. Median age was 49 in the first group and 59 in the second group of patients (p = 0.04). In the first group, all patients (100%) had unilateral lesions, and in the second group, 94% had bilateral tumors (p < 0.000001). In the first group, a tumor size equal or greater than 10 cm was present in 80% of patients, and the same was true for 21% of patients in the second group. The mille-feuille sign was present in 30% of patients from the first group and in 64% of patients from the second group. In the first group of patients, TTP was 410 and Perf.Max Enhancement was 141; in the second group, they were, respectively, 154 and 167 (p = 0.0001 and p = 0.5). Median ADC values in the first group were significantly higher in the first group than in the second group (p < 0.01). Conclusions: Significant differences in TTP and ADC values as well as in Seidman criteria enable reliable differentiation between the analyzed groups of tumors.

Expression of Trefoil Factor 1 (TFF1) in Cancer: A Tissue Microarray Study Involving 18,878 Tumors.

Background/Objectives: Trefoil factor 1 (TFF1) plays a role in the mucus barrier. Methods: To evaluate the prevalence of TFF1 expression in cancer, a tissue microarray containing 18,878 samples from 149 tumor types and 608 samples of 76 normal tissue types was analyzed through immunohistochemistry (IHC). Results: TFF1 staining was detectable in 65 of 149 tumor categories. The highest rates of TFF1 positivity were found in mucinous ovarian carcinomas (76.2%), colorectal adenomas and adenocarcinomas (47.1-75%), breast neoplasms (up to 72.9%), bilio-pancreatic adenocarcinomas (42.1-62.5%), gastro-esophageal adenocarcinomas (40.4-50.0%), neuroendocrine neoplasms (up to 45.5%), cervical adenocarcinomas (39.1%), and urothelial neoplasms (up to 24.3%). High TFF1 expression was related to a low grade of malignancy in non-invasive urothelial carcinomas of the bladder (p = 0.0225), low grade of malignancy (p = 0.0003), estrogen and progesterone receptor expression (p < 0.0001), non-triple negativity (p = 0.0005) in invasive breast cancer of no special type, and right-sided tumor location (p = 0.0021) in colorectal adenocarcinomas. Conclusions: TFF1 IHC has only limited utility for the discrimination of different tumor entities given its expression in many tumor entities. The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types.

A Rare Case of Primary Ovarian Mucinous Carcinoma with Signet-Ring Cells and Literature Review.

The presence of signet-ring cells in the ovary is almost always associated with metastatic mucinous carcinomas known as Krukenberg tumors. Here we report a primary ovarian mucinous carcinoma with signet-ring cells, which is scarcely encountered, and a review of the literature to summarize the clinical and morphological features of these tumors. The patient was a 26-year-old female who had a large multicystic lesion in the right ovary. Macroscopic examination of the cyst revealed a 30 cm-sized multicystic lesion filled with mucinous material. The capsule was intact, and there was no surface involvement. Microscopically, a multicystic mucinous tumor with a predominantly borderline background and three well-demarcated nodules composed of signet ring cells without desmoplastic stroma were noted in the cyst wall. There was only one invasive focus seen. Immunohistochemically, conventional mucinous areas were diffusely positive for Keratin 7 and Keratin 20, and focally positive for PAX8, while negative for CDX2. Signet ring cells were positive for Keratin 20, CDX2, and Keratin 7, while negative for PAX8. In the systemic examinations, no potential primary site was found. The patient has not received any adjuvant treatment and has been followed for six years without disease, which is the longest follow-up time among previously reported cases. Signet ring cells can be present in primary ovarian mucinous carcinomas. The distinction from the more frequently seen metastatic carcinomas needs a complete evaluation of clinicopathological findings. Early-stage primary mucinous carcinomas having localized signet-ring cell nodules seem to have favorable prognosis without adjuvant treatment.

A new method for network bioinformatics identifies novel drug targets for mucinous ovarian carcinoma.

Mucinous ovarian carcinoma (MOC) is a subtype of ovarian cancer that is distinct from all other ovarian cancer subtypes and currently has no targeted therapies. To identify novel therapeutic targets, we developed and applied a new method of differential network analysis comparing MOC to benign mucinous tumours (in the absence of a known normal tissue of origin). This method mapped the protein-protein network in MOC and then utilised structural bioinformatics to prioritise the proteins identified as upregulated in the MOC network for their likelihood of being successfully drugged. Using this protein-protein interaction modelling, we identified the strongest 5 candidates, CDK1, CDC20, PRC1, CCNA2 and TRIP13, as structurally tractable to therapeutic targeting by small molecules. siRNA knockdown of these candidates performed in MOC and control normal fibroblast cell lines identified CDK1, CCNA2, PRC1 and CDC20, as potential drug targets in MOC. Three targets (TRIP13, CDC20, CDK1) were validated using known small molecule inhibitors. Our findings demonstrate the utility of our pipeline for identifying new targets and highlight potential new therapeutic options for MOC patients.

Investigating age and ethnicity as novel high-risk phenotypes in mucinous ovarian cancer: retrospective study in a multi-ethnic population

ObjectivesPrimary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age...

Mucinous Carcinoma of Ovary in a 15-Year-Old Girl, A Rare Case Report and Literature Review.

Ovarian epithelial tumors are common in adults, and the median patient age at presentation is 55 years. In children, epithelial tumors are rare and mostly benign. Mucinous cystadenocarcinoma is reported in only 11 cases less than 15 years old. This report describes the case of a 15-year-old postmenarchal Omani girl with ovarian mucinous carcinoma. She was admitted with severe epigastric pain and abdomen distension. CT scan showed a huge cystic lesion arising from the left adnexa filling the entire abdominal and pelvic cavity. The patient underwent laparotomy with left ovarian cystectomy and omental biopsy which revealed a 35 x 30 cm left ovarian cyst filled with turbid straw color fluid. Histopathology was reported as mucinous carcinoma. The patient later underwent cytoreductive surgery with left salpingo-oophorectomy, omentectomy, appendicectomy, and lymph node dissection that were negative for malignancy or metastatic disease. During follow-up, she developed a lymphocele in the pelvic cavity that was drained. There were no other significant issues during follow-up, as well as no evidence of recurrence or metastasis. Epithelial tumors of the ovary are rare in young girls, with malignant tumors being exceedingly rare. Fertility-sparing surgery is adopted over radical surgery in these patients, even though the recurrence rates with this treatment protocol are high. All cases should be under follow-up to look for recurrence and timely management.

Immunohistochemical expression of SATB2 and PAX8 in differentiating primary from metastatic ovarian mucinous neoplasms.

Accurate stratification of an ovarian mucinous neoplasm as primary or secondary is always challenging as they show overlapping histomorphological and immunohistochemical features. Immunohistochemical staining for SATB2 and PAX8 was performed on 80 cases of mucinous ovarian neoplasms subdivided into 53 primary [25 primary ovarian mucinous carcinomas (POMCs) and 28 mucinous borderline tumors (MBTs)] and 27 secondary (12 of colonic origin, 7 of appendiceal origin, and 8 of gastric origin). Expression was correlated with different clinicopathologic parameters. PAX8-positive immunostaining was detected in 38 out of 53 cases (71.69%) of primary ovarian mucinous neoplasms (POMNs) with null positivity in the secondary ovarian mucinous tumors (0/27). SATB2-positive expression was detected in 16 out of 27 cases (59.26%) of the secondary ovarian mucinous tumors. None of the studied POMNs showed any positive immunostaining for SATB2 (0/53). A profile of SATB2-/PAX8+ and SATB2+/PAX8- can be used to differentiate POMNCs from secondary ovarian mucinous tumors of GI origin, respectively, with 100% specificity. PAX8 expression is associated with some clinicopathologic parameters providing the basis for the possible usage of PAX8 as prognostic marker.

Multimodal diagnostic strategies and precision medicine in mucinous ovarian carcinoma: a comprehensive approach.

Mucinous ovarian carcinoma (MOC) represents a distinct entity within ovarian malignancies, characterized by diagnostic challenges due to its rarity and the potential overlap with other tumor types. The determination of tumor origin is important for precise postsurgical treatment. This article highlights the accurate diagnosis and management of MOC, including the use of imaging modalities, serological tumor markers, immunohistochemistry, and genomic analyses. Transabdominal and transvaginal ultrasonography, complemented by MRI and CT, plays a pivotal role in differentiating MOC from other mucinous tumors and in surgical planning, particularly for fertility preservation. Serological markers like CA19-9, CA-125, and CEA, though not definitive, provide valuable preoperative insights. Immunohistochemistry aids in distinguishing primary MOC from metastatic mucinous carcinomas, while genomic profiling offers the potential for precision medicine through the identification of specific molecular signatures and treatment susceptibilities. Despite advancements in diagnostic techniques, no single method conclusively differentiates between primary and metastatic tumors intraoperatively. The paper reviews the origins, diagnosis, and differential diagnosis of primary mucinous ovarian carcinoma highlights the need for a multimodal diagnostic approach and advocates for the inclusion of MOC patients in clinical trials for personalized therapies, recognizing the heterogeneity of the disease at the molecular level.

The survival benefit associated with complete macroscopic resection in epithelial ovarian cancer is histotype-specific.

Complete macroscopic resection (CMR) is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high grade serous ovarian carcinoma (HGSOC), and the benefit of CMR in other histotypes is poorly characterised. We sought to determine which histotypes derive the greatest benefit from CMR to better inform future decisions on radical cytoreductive efforts. We performed multivariable analysis of disease-specific survival (DSS) across two independent patient cohorts to determine the magnitude of benefit associated with CMR within each histotype. Across both cohorts (Scottish, n = 1622; SEER, n = 18947), CMR was associated with prolonged DSS; this was more marked in the Scottish cohort (multivariable HR 0.44, 95%CI 0.37-0.52 vs 0.59, 95%CI 0.57-0.62 in SEER). In both cohorts, clear cell ovarian carcinoma (CCOC) was among the histotypes to benefit most from CMR (multivariable HR 0.23 and 0.50 in Scottish and SEER cohorts); HGSOC cases demonstrated highly significant and clinically meaningful survival benefit, but this was of lower magnitude than in CCOC and endometrioid ovarian carcinoma (EnOC) across both cohorts. The benefit derived in low grade serous ovarian carcinoma is also high (multivariable HR 0.27 in Scottish cohort). CMR was associated with prolonged survival in mucinous ovarian carcinoma (MOC) patients in the SEER cohort (multivariable HR 0.65), but the associated failed to reach statistical significance in the Scottish cohort. The overall ovarian cancer patient population demonstrates significant survival benefit associated with CMR; however, the magnitude of benefit differs between histotypes.

GATA4 is diagnostically useful for distinguishing primary ovarian mucinous carcinomas from metastatic colorectal adenocarcinomas to the ovary.

Determining the primary origin of an ovarian mucin-producing carcinoma can be challenging at times because some metastases of primary colorectal origin may exhibit gross, microscopic, and/or immunohistochemical features that overlap with those of primary ovarian mucinous carcinomas (OMCs). We hypothesized that GATA binding protein 4 (GATA4) might be a novel, useful marker for differentiating primary OMCs from metastatic colorectal adenocarcinomas to the ovary. For comparison with the usefulness of other markers (special AT-rich sequence-binding protein 2 (SATB2) and caudal type homeobox 2 (CDX2)), we elucidated the expression profiles of GATA4 in OMCs, colorectal non-mucinous adenocarcinomas (CNMACs), and colorectal mucinous adenocarcinomas (CMACs) using immunohistochemistry. We confirmed GATA4 expression (H-score ≥50 points) in 93%, SATB2 in 0%, and CDX2 in 64% of 14 OMCs. GATA4 was expressed in 13%, SATB2 in 90%, and CDX2 in 93% of 30 CNMACs. GATA4 was expressed in 20%, SATB2 in 73%, and CDX2 in 100% of 30 CMACs. The expression of GATA4 in a mucus-producing ovarian tumor strongly supports it being a primary OMC rather than a metastatic colorectal carcinoma: GATA4 expression indicates OMC and SATB2 expression indicates colorectal adenocarcinoma. However, three cases of colorectal adenocarcinoma were GATA4-positive and SATB2-negative, so the GATA4/SATB2 marker combination is not absolute for determining the primary site. Further research for more markers is necessary to find the ideal combination.

A rare case of synchronous bilateral ovarian cancer with combined clear cell and mucinous carcinomas and brain metastases.

Although ovarian cancer is generally unilateral, a few cases of bilateral ovarian cancer have been reported, most of which originate from metastases of unilateral ovarian cancer. However, synchronous primary bilateral ovarian cancer (SBOC), comprising two different histological types of ovarian cancer, is extremely rare, with limited reports on its clinical course and prognosis. Herein, we report the case of a 56-year-old postmenopausal Japanese woman with stage IVB SBOC with combined left ovarian clear cell and right ovarian mucinous carcinomas. The patient underwent surgery and received postoperative taxane/platinum-based chemotherapy, which temporarily reduced the tumor size. However, an increase in tumor size and brain metastases were subsequently identified. Treatment was accordingly discontinued, and the patient died of the disease 12months after diagnosis. In this case report, we detail the clinical course of a case of SBOC. To the best of our knowledge, this is the first report of SBOC with combined histological types of clear cell and mucinous carcinomas, and it is also the first report of SBOC with the eventual discovery of brain metastases.

Ovarian carcinosarcoma is highly aggressive compared to other ovarian cancer histotypes

BackgroundOvarian carcinosarcoma (OCS) is an unusual ovarian cancer type characterized by distinct carcinomatous and sarcomatous components. OCS has been excluded from many of the pan-histotype studies of ovarian carcinoma, limiting our understanding of its behavior.MethodsWe performed a multi-cohort cross-sectional study of characteristics and outcomes in ovarian cancer patients from Scotland (n=2082) and the Surveillance, Epidemiology and End Results Program (SEER, n=44946) diagnosed with OCS or one of the other major histotypes: high grade serous (HGSOC), endometrioid (EnOC), clear cell (CCOC), mucinous (MOC) or low grade serous ovarian carcinoma (LGSOC). Differences in overall survival were quantified using Cox regression models to calculate hazard ratios (HR).ResultsAcross both cohorts, OCS patients were significantly older at diagnosis compared to all other histotypes (median age at diagnosis 69 and 67 in Scottish and SEER cohorts) and demonstrated the shortest survival time upon univariable analysis. Within the Scottish cohort, 59.3% and 16.9% of OCS patients presented with FIGO stage III and IV disease, respectively; this was significantly higher than in EnOC, CCOC or MOC (P&amp;lt;0.0001 for all), but lower than in HGSOC (P=0.004). Multivariable analysis accounting for other prognostic factors identified OCS as independently associated with significantly shorter survival time compared to HGSOC, EnOC, LGSOC and MOC in both the Scottish (multivariable HR vs OCS: HGSOC 0.45, EnOC 0.39, LGSOC 0.26, MOC 0.43) and SEER cohorts (multivariable HR vs OCS: HGSOC 0.59, EnOC 0.34, LGSOC 0.30, MOC 0.81). Within the SEER cohort, OCS also demonstrated shorter survival compared to CCOC (multivariable HR 0.63, 95% CI 0.58-0.68), but this was not replicated within the Scottish cohort (multivariable HR for CCOC: 1.05, 95% CI 0.74-1.51). Within early-stage disease specifically (FIGO I-II or SEER localized stage), OCS was associated with the poorest survival of all histotypes across both cohorts. In the context of late-stage disease (FIGO III-IV or SEER distant stage), OCS, MOC and CCOC represented the histotypes with poorest survival.ConclusionOCS is a unique ovarian cancer type that affects older women and is associated with exceptionally poor outcome, even when diagnosed at earlier stage. New therapeutic options are urgently required to improve outcomes.

The frequency and prognostic role of P53 and P16 immunoexpression in primary ovarian mucinous tumors

BackgroundPrimary ovarian mucinous tumors are uncommon. Factors leading to invasive progression and metastatic disease have not been fully delineated yet. The aim of this study is to determine the rates of p53 and p16 immunoexpressions in primary ovarian mucinous tumors, to investigate their relationship with clinicopathologic factors and their impact on prognosis and survival. MethodsSeventy-eight primary ovarian mucinous tumors (30 mucinous cystadenomas, 30 mucinous borderline tumors (MBOT), 18 mucinous carcinomas (MOC)) were evaluated immunohistochemically with p53 and p16 staining. The demographic, clinicopathological data, and postoperative follow-up findings of the patients were analyzed. ResultsMutation-type p53 staining was present in 1/30 (3.3 %) cystadenoma, 10/30 (33.3 %) MBOT and 9/18 (50 %) MOC (p = 0.001). p16 overexpression was detected in 3/30 (10.0 %) MBOT and 5/18 (27.8 %) MOC, but not in any cystadenoma (p = 0.04). The frequency of mutation-type p53 staining in MBOTs with microinvasion was higher (71.4 %) than in those without (28.6 %, p = 0.026). The frequencies of p16 or p53 mutations were similar in MBOTs with and without intraepithelial carcinoma, or mural nodule (p > 0.05). In MOCs with ovarian surface involvement, mutation-type p53 staining was detected in 66.7 % (6/9) and p16 overexpression in 55.6 % (5/9) of the cases. A significant difference was found between MOCs with or without ovarian surface involvement regarding the frequency of p16 overexpression (p = 0.029). Any relationship was not detected between survival and p53 and p16 expression in MOCs (p > 0.05). Conclusionp53 and p16 mutation rates were higher in MOCs compared to mucinous cystadenomas and MBOTs and suggest a relevant role in the development of primary ovarian mucinous carcinoma, however further studies are needed in this regard.

Immunohistochemistry as an adjunct for challenging histological patterns of borderline Brenner tumors: An illustrative study of 4 cases

Borderline Brenner tumors (BBT) have a range of morphology that shows considerable overlap with that of malignant Brenner tumors (MBT). In particular, two histological patterns of BBT can be particularly challenging: 1) BBT with intraepithelial carcinoma (BBT-IEC) and 2) BBT with a small nested pattern (BBT-SNP). BBT-IEC is characterized by a tumor with the low-power non-infiltrative silhouette of a conventional BBT, but with increased cytological atypia and mitotic activity similar to that of MBT. Conversely, BBT-SNP is characterized by a complex proliferation of small tumor nests that closely resemble the infiltrative growth pattern of MBT, but without the obligate cytologic atypia and mitotic activity of MBT.We suggest that the combination of p16, p53 and Ki-67 may be helpful in distinguishing these 2 patterns of BBT from both conventional BBT and from MBT. While both conventional BBT and BBT-IEC show a null pattern of p16 expression, our case of BBT-IEC showed aberrant p53 overexpression, albeit with a maturation pattern similar to that described for TP53 mutant mucinous ovarian carcinoma and differentiated vulvar intraepithelial neoplasia (dVIN). Similarly, while BBT-SNP shows an infiltrative-like growth pattern similar to that of MBT, our case also showed a wild-type pattern of p53 expression and a Ki-67 proliferative index similar to areas with conventional BBT histology. In conclusion, in our small case series, we show that the use of immunohistochemistry for p53 and Ki-67 may help to distinguish challenging patterns of BBT from MBT. Further studies are needed to validate this finding in a larger case cohort.

Perioperative management of a patient with unexpectedly detected early-stage ovarian mucinous carcinoma combined with progressive bulbar paralysis: a case report and literature review

BackgroundGiant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases.Case presentationIn this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml.ConclusionsGOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.

HER2-low and Overexpression in Mucinous Ovarian Cancer: Analysis of ASCO/CAP and ToGA Immunohistochemical Scoring.

Mucinous ovarian carcinoma is an uncommon malignancy characterized by resistance to chemotherapy and poor survival in the metastatic setting. HER2 amplification is a frequent late event in carcinogenesis, yet the incidence of HER2-low in mucinous ovarian carcinoma is unknown. Further, the optimal method for determining overexpression in these tumors is not established. We sought to assess the ASCO/CAP and ToGA trial scoring methods for HER2 IHC with correlation to FISH, p53, and mismatch repair protein status and to determine the incidence of HER2-low in mucinous ovarian carcinoma. A total of 29 tumors from 23 patients were included. Immunohistochemistry for HER2, p53, MLH1, PMS2, MSH2, and MSH6 was performed. Scoring was performed according to the ASCO/CAP and ToGA trial criteria. HER2 FISH was performed and scored according to the ASCO/CAP criteria. The proportion of HER2-low, defined as 1+ or 2+ staining with negative FISH, was determined. Using ASCO/CAP, 26% demonstrated 3+ while 35% demonstrated 2+ staining. Using ToGA, 30% demonstrated 3+ while 57% demonstrated 2+ staining. By FISH, 26% were positive for HER2 amplification. Both systems captured all FISH-positive cases; the use of ASCO/CAP resulted in fewer equivocal and false-positive cases. Among HER2-negative cases, 88% were HER2-low. Aberrant p53 expression was detected in 55% of cases; mismatch repair deficiency was not identified in any cases. ASCO/CAP guidelines are accurate and resource-effective in determining HER2 overexpression in mucinous ovarian carcinoma. HER2-low is common in these tumors; further studies to determine the role of HER2-targeted therapy including antibody-drug conjugates are indicated.

Outcomes of patients with early stage mucinous ovarian carcinoma: a Dutch population-based cohort study comparing expansile and infiltrative subtypes

ObjectiveThis study aimed to assess the outcomes of patients with early stage mucinous ovarian carcinoma based on subtype (expansile vs infiltrative).MethodsWe retrospectively analyzed all surgically treated patients with mucinous ovarian...

Abstract 4685: The identification of new therapeutic targets in mucinous ovarian carcinoma

Abstract Background: Epithelial ovarian cancer (EOC) is the second cause of death among gynaecological cancersworldwide. Mucinous ovarian carcinoma (mEOC) accounts for 3-5% of all EOCs, and when diagnosed at anadvanced stage its prognosis is very poor mainly for its limited chemosensitivity. PLK1 is a member of thewell-conserved serine/threonine kinase family, that plays a key role in the progression of mitosis, in the G2/Mcheckpoint regulation, DNA damage replication, stress response, and cell death pathways. mEOC has beenshown to be sensitive to PLK1 inhibition both with siRNA and small molecule inhibitor (onvansertib). Giventhis background and the need for new therapeutic approaches in mEOC, the purposes of this work were toidentify new therapeutic targets in mEOC using CRISPR/Cas9 lentivirus libraries and to find synthetic lethalpartners with the PLK1 inhibitor onvansertib. Methods: We used three different mucinous cell lines: MCAS,EFO27, TOV2414, overexpressing Cas9 gene. We evaluated the Cas9 expression through Western Blotanalysis, and the Cas9 activity through a Fluorescent Activated Cell Sorter- based-GFP assay. We used twodifferent lentiviral gRNAs Libraries (Bassik Library Human CRISPR Deletion Library - Apoptosis and cancer(Addgene #101926)/Drug targets, kinases, and phosphatases (Addgene #101927)). The EFO27 Cas9 cells wereused for the screening experiment. Cells were infected with the lentiviral libraries at MOI of 0.3 and put inpuromycin selection. Six days after puromycin addition (Time point 0) 30x10^6 cells were collected forsequencing. The remaining 30x10^6 cells were split in two: control cells and cells treated with a subtoxic doseof onvansertib (IC30). After 7 days (Time point 1) 30x10^6 cells for each condition were collected forsequencing. The infection of libraries was performed alone and in combination with sub-toxic onvansertibtreatment, to identify genes important for mucinous carcinoma cell survival, and those genes in syntheticlethality with onvansertib. Results: Bioinformatic analyses comparing control cells (time 1 vs time 0) andPLK1 treated and non -treated cells (time 1) allowed the generation of a gene ranking list, including genesinvolved in survival of EFO27 cells like ZC2HC1C, RPA2, POLE3, KIN, TUBG1, SMC2, CDC26, CDC42, HOXA9,TAF10, DCLRE1C, SENP1, MRPS31, COPS2; and genes in synthetic lethality with PLK1 treatment, like JUND,CARD9, BCL2L2. Validation experiments are ongoing and will be presented and discussed. Conclusion: Using a CRISPR-based approach, we identified genes that either alone or in combination with PLK inhibitioncould have therapeutic value in mEOC. Citation Format: Serena Petrella, Marika Colombo, Mirko Marabese, Chiara Grasselli, Andrea Panfili, Ilaria Craparotta, Maria Chiara Barbera, Giada Andrea Cassanmagnago, Marco Bolis, Giovanna Damia. The identification of new therapeutic targets in mucinous ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4685.