Introduction: Endometrial carcinoma is the most common invasive cancer of the female genital tract. Serous carcinoma of endometrium is highly aggressive and has a predilection for deep myometrial and lymphovascular invasion, peritoneal and distant metastatic spread. HER2/neu is an important prognostic protein in high-grade and higher-stage endometrial serous carcinomas Aim: To study the expression of HER2/neu in relation to tumour grade in endometrial carcinoma. Materials and Methods: The present cross-sectional study was conducted in the Department of Pathology, Government medical college, Thrissur, Kerala, India, over a period of 18 months from 1st January 2018 to 30th June 2019. A total of 63 cases of both hysterectomy specimens and endometrial biopsies whose histopathologic diagnosis was endometrial adenocarcinoma were included. Four micrometer thick sections were obtained for Haematoxylin and Eosin (H&E) and immunohistochemical staining with rabbit monoclonal HER2 antibody following antigen retrieval was done. H&E staining was done to assess the tumour grade. HER2/neu staining was evaluated using regular light microscope at the magnification of 40x. The Immunohistochemistry (IHC) score was determined by evaluating subcellular localisation, circumferential versus incomplete staining, intensity and the percentage of cells positive. Intensity of HER2 expression was graded according to the 2014 American Society of Clinical Oncology/College of American Pathologist (ASCO/CAP) guidelines for HER2 reporting. Data thus obtained was analysed using software Statistical Package for Social Sciences (SPSS) version 20.0. The statistical test used is the Fisher’s-exact test and p-value<0.05 was considered statistically significant. Results: Most of the patients were in the age group of 51-60 years (23 out of 63 patients, 36.50%). Among the 63 patients seven were nulliparous and 56 were post menopausal women. Most of the patients presented with complaints of post menopausal bleeding which was noted in 85.71% of patients (54 out of 63). More than half of myometrial invasion was noted in 33 cases of hysterectomy specimens. HER2 positivity (score 2 and score 3) was observed in 7 (11.11%) cases. None of the grade 1 endometrial carcinoma showed HER2 positivity. Grade 2 endometrial carcinoma showed HER2 positivity in 1 (6.67%) case. Grade 3 tumours showed HER2 positivity in 6 (28.57%) cases. Compared to grade 1 and grade 2 endometrial carcinoma, grade 3 endometrial carcinoma showed increased HER2 expresssion. A statisticaly significant association between HER2 expression and tumour grade was obtained (p-value=0.004). Conclusion: As tumour grade in endometrial adenocarcinoma increases expression of HER2/neu also increases. A statistically significant association between HER2 expression and tumour grade was obtained (p-value=0.004). The study suggests that endometrial carcinoma shows HER2/neu expression in significant proportion of cases and its expression is more in highgrade endometrial carcinoma. Patients with HER2/neu positive endometrial carcinoma may benefit from adjuvant HER2/neu targeted therapies like trastuzumab. Further clinical studies are necessary to establish the prognostic and therapeutic significance of HER2/neu in endometrial adenocarcinoma.

Progestin and vitamin D synergistically inhibit fallopian tube carcinogenesis.

Peritoneal cancer risk after risk reducing salpingo-oophorectomy, impact of mutational status and STIC lesions.

A 57-year-old woman presented with fever was incidentally found to have a large hepatogastric space mass with coarse calcifications on CT, accompanied by a markedly elevated serum CA-125 level (3082U/mL). 18F-FDG PET/MR revealed intense metabolic activity (SUVmax= 10.82) and restricted diffusion without ascites, while both ovaries appeared unremarkable. Pathology confirmed primary peritoneal high-grade serous carcinoma (PPHGSC). This case illustrates atypical imaging features of this rare malignancy, including lesion localization, coarse calcification, and absence of ascites.

Ovarian Cancer Screening and Ovarian-Adnexal Reporting and Data System.

The nuclear pore complex (NPC) component TPR has emerged as a multifunctional scaffold implicated in mitosis, chromatin organization, mRNA export, and genome stability. However, TPR's role in mitogenic signal transduction remains largely unexplored. Here, we investigate whether nucleoporin TPR functions as a MAPK-regulated nuclear component that modulates mitogenic signals initiated at the plasma membrane-including EGFR activation-and their transcriptional output. Transcriptomic profiling reveals that TPR depletion reshapes EGF-induced, MAPK-responsive gene expression, including altered expression of MAPK pathway components and enhanced induction of the immediate-early gene FOS. Functionally, TPR-depleted cells exhibit increased FOS induction upon EGF stimulation and altered EGF-driven cell-cycle progression. Using a novel phospho-specific monoclonal antibody, we show that TPR is phosphorylated at Ser2155 following EGFR activation via the canonical RAS-RAF-MEK-ERK MAPK cascade, placing TPR downstream of MAPK pathway activation. This phosphorylation is suppressed by clinically used EGFR and BRAF inhibitors and, conversely, is constitutively induced by oncogenic RAS and BRAF, indicating that Ser2155 phosphorylation reflects MAPK pathway activity. In vivo, CRISPR/Cas9-engineered Tpr haploinsufficient mice show changes in MAPK pathway regulatory gene expression in bulk spleen RNA-seq, consistent with findings in human cells, and enhanced Fos induction in splenocytes upon CD3/CD28 stimulation, together suggesting a conserved association between TPR levels and altered MAPK-related transcriptomic profiles. Finally, immunohistochemical analysis reveals elevated TPR phosphorylation in serous ovarian carcinoma and heterogeneous phosphorylation patterns in triple-negative breast cancer, two tumor types frequently characterized by MAPK pathway hyperactivation. Together, these findings uncover a previously unappreciated role for TPR as a MAPK-responsive nuclear factor and support a model in which NPC-associated components fine-tune mitogen-induced transcriptional responses.

Purpose Uterine serous carcinoma (USC) is known for its aggressive behavior, high recurrence rate, and poor prognosis. Despite its clinical importance, personalized prognostic tools for USC are limited. This study aimed to develop and externally validate a nomogram to help gynecologic oncologists accurately predict patient survival and create personalized treatment regimens. Methods A retrospective cohort study was conducted using clinical records of USC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2000–2022). Patients were randomly split into training and internal validation cohorts in a 7:3 ratio. An independent external validation cohort was also used from Fujian Cancer Hospital. Prognostic factors affecting overall survival (OS) were identified using univariate and multivariate Cox regression. Model performance was evaluated using time-dependent ROC curves, calibration plots, and decision curve analysis (DCA). Results The study included 8,204 USC patients from both SEER and Fujian Provincial Cancer Hospital cohorts. Multivariate Cox regression showed that age, FIGO stage, T stage, N stage, radiotherapy, chemotherapy, and surgery were significant independent prognostic factors for OS (all P < 0.05). The nomogram incorporating these variables displayed robust discriminatory capacity, yielding 5-year OS prediction AUC values of 0.79, 0.78, and 0.72 across the three distinct patient cohorts. Calibration plots demonstrated good agreement between predicted and observed outcomes. DCA indicated substantial clinical benefit. Survival analysis revealed significant differences in OS between the high-risk and low-risk groups (P < 0.05). Conclusions A reliable and well−validated nomogram was established for predicting OS in USC patients. This predictive tool supports clinicians in performing individualized risk stratification, guiding patient counseling, and optimizing adjuvant therapeutic decisions.

Detecting chromosomal copy-number alterations together with protein-defined cell states in intact tissue is critical for understanding early clonal evolution and microenvironmental interactions in cancer. We developed ORION-FISH, which integrates high-plex tissue imaging with a morphology-preserving DNA-FISH workflow and single-cell registration, yielding measurements concordant with clinical FISH. In High Grade Serous Ovarian Carcinoma (HGSOC), ORION-FISH recapitulated known chromosomal changes while revealing subclonal heterogeneity missed by targeted sequencing. Applied to serous tubal intraepithelial carcinomas (STICs), precursors of HGSOC, ORION-FISH identified intermixed epithelial cells with MYC or CCNE1 copy-number gains, as well as concurrent alterations associated with distinct immune microenvironments. In addition, epithelial cells with MYC and CCNE1 copy-number gains were detected in morphologically normal fallopian tube epithelium, along with rare MDM4 increases across epithelial lineages. Together, ORION-FISH provides a framework linking chromosomal copy number states to protein-defined phenotypes within preserved tissue architecture, enabling context-aware interrogation of early copy-number diversification at single-cell resolution.

Abstract Background: Platinum-resistant ovarian cancer (PROC) and clear cell gynecologic cancer (CCGC) are associated with poor prognoses and have limited effective treatment options. PROC has a recurrence rate of approximately 70%, while CCGC, a rare histologic subtype, demonstrates resistance to most standard therapies. These unmet clinical needs underscore the importance of developing novel therapeutics to improve patient outcomes. Immune checkpoint inhibitors have shown promising preliminary antitumor activity in PROC and CCGC, although they are not currently approved for either indication. Lorigerlimab is an investigational bispecific (PD-1 x CTLA-4), tetravalent DART® molecule. It is engineered to enhance CTLA-4 blockade in a PD-1-binding-dependent manner, intended to improve activity in the tumor microenvironment while minimizing off-tumor toxicity. Preclinical and early-phase clinical data support lorigerlimab immunomodulatory activity and tolerability. This study investigates the efficacy and safety of lorigerlimab monotherapy in patients with PROC and CCGC. Methods: This open-label, multicohort, multi-institutional, phase 2 study (NCT06730347) evaluates lorigerlimab monotherapy in participants with PROC (cohort A) or CCGC (cohort B). Cohort A utilizes a Simon’s two-stage design to enroll up to 40 participants and cohort B will enroll up to 20 participants. Participants receive lorigerlimab intravenously every 3 weeks for up to 35 cycles or until disease progression, unacceptable toxicity, or withdrawal. The primary objective is to evaluate the antitumor activity as measured by objective tumor response. Secondary objectives include characterization of safety, tolerability, and evaluation of efficacy by duration of response, disease control rate, progression-free survival, and change in tumor size from baseline. Eligible participants must have persistent or recurrent high-grade serous ovarian carcinoma or clear cell gynecologic cancers with at least 50% clear cell histomorphology. Participants with PROC must have received at least one and up to three prior lines of systemic therapy, which may include prior bevacizumab. Individuals with a germline or somatic BRCA mutation must have received PARP inhibitor therapy. Participants with CCGC must have received at least one prior line. All participants must have good functional status, measurable disease, adequate organ function, and no contraindications to immunotherapy. Individuals with primary platinum-refractory disease are excluded. Prior use of checkpoint inhibitor therapy is permitted for participants with clear cell endometrial or clear cell cervical cancer. Tumor assessments occur every 9 weeks for the first 54 weeks, then every 12 weeks until treatment discontinuation. Enrollment commenced in May 2025 and is ongoing. Citation Format: Helen D. Clark, Kelly M. Rangel, Shawana N. Richard, Jichao Sun, Pepi Pencheva, Chad Hamilton, Amir A. Jazaeri. A phase 2 multicohort study to evaluate lorigerlimab (PD-1 x CTLA-4) in participants with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT279.

Natural killer (NK) cells contribute to tumor immunosurveillance, yet their heterogeneity across cancer types remains incompletely understood. Transcriptomic, spatial, and functional assays reveal that non-small cell lung carcinoma (NSCLC) is enriched in NK cells that mediate clinically relevant effector functions, whereas high-grade serous ovarian carcinoma (HGSOC) contains dysfunctional NK cells that express co-inhibitory receptors including NKG2A. Analysis of HGSOC patient samples and syngeneic mouse models indicates a crosstalk between NK cells and CD8⁺ T cells critical for effective antitumor immunity. Depletion of either population leads to phenotypic impairment of the reciprocal one. Blocking NKG2A restores NK cell cytotoxicity and promotes CD8⁺ T cell responses, significantly improving the efficacy of PD-1 blockade in murine HGSOC models. Thus, NK cells and CD8⁺ T cells engage in a functional interplay of immunological relevance. Moreover, the NKG2A-HLA-E axis represents a clinically actionable immunological checkpoint in tumors with impaired NK cell functions.

Background: High-grade serous ovarian carcinoma (HGSOC) is the most common and lethal subtype of epithelial ovarian cancer and is frequently diagnosed at advanced stages. Because currently available blood-based biomarkers have limited performance in early-stage disease, there is a need to identify circulating biomarker candidates associated with early-stage HGSOC. In this retrospective multi-institutional case-control study, we evaluated whether serum extracellular vesicle (EV)-associated protein signatures distinguish early-stage HGSOC from healthy controls. Methods: Serum samples (n = 252) were obtained retrospectively from multiple institutions and included healthy controls and patients with early- and advanced-stage HGSOC. EV-associated proteins were profiled using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and proximity extension assay (PEA) to identify candidate proteins enriched in early-stage HGSOC. Selected candidates were evaluated by enzyme-linked immunosorbent assay (ELISA), and tissue-level expression was examined in early-stage HGSOC specimens. A multimarker combination model was generated using a smoothed empirical estimate of hyper-volume under the manifold (SHUM) approach and internally assessed by leave-one-out cross-validation. Results: Ten EV-associated serum proteins were prioritized on the basis of differential expression and fold change and were confirmed to be expressed in early-stage HGSOC tissues. In ELISA-based analyses, the combined 10-protein EV panel distinguished early-stage HGSOC from healthy controls with an area under the curve (AUC) of 0.99 in the study dataset, whereas MUC16 (CA-125) showed substantially lower performance in this comparison. The SHUM-based model yielded a true-positive rate of 0.971, a false-positive rate of 0.057, and a Matthews correlation coefficient of 0.915 in the analyzed cohort. Several candidate proteins were differentially enriched in EV fractions but not in matched whole serum. Conclusions: Serum EV-associated proteins are altered in early-stage HGSOC and define a multi-protein signature associated with this disease state in a retrospective case-control setting. These findings support further evaluation of EV-based biomarker candidates in clinically representative and prospectively collected cohorts that include benign gynecologic conditions, symptomatic patients, and pre-diagnostic samples.

High-grade serous ovarian carcinoma (HGSC) is the sixth leading cause of cancer-related death among women. Most tumors arise from the Fallopian tubal epithelium (TE), exhibit numerous mutations, and present heterogenous pathological features. However, the contribution of specific mutation combinations to cellular transformation, pathological phenotype and chemotherapeutic responses remains unclear. We used a mouse TE organoid platform for combinatorial CRISPR mutagenesis of 20 candidate HGSC driver genes. Besides Trp53, mutations in Nf1, Cdkn2a and Map2k4 were the most prevalent in phenotypically transformed organoids. Map2k4 mutant organoids transplanted into mice predominantly yielded papillary-glandular carcinomas, whereas those with Nf1 mutations were more mesenchymal-like. Map2k4 mutant cells were particularly sensitive to paclitaxel, and Rho kinase inhibitor (ROCKi) increased trametinib sensitivity in both Map2k4- and Nf1-mutant organoids. This organoid mutagenesis strategy is powerful for unraveling the genetic and phenotypic complexity of HGSC, and identified Map2k4 as a potential therapeutic target in select HGSC cases.

Patients with advanced or recurrent endometrial cancer (EC) have limited treatment options. The development of antibody-drug conjugates (ADCs) offers new treatment strategies by targeted delivery of cytotoxic payloads, including conventional chemotherapy, to cancer cells. An ADC targeting Claudin-6 is currently in clinical testing however expression patterns of Claudin-6 has not been thoroughly explored in EC. Membrane expression of Claudin-6 was evaluated by immunohistochemistry in a large, prospectively collected EC cohort with 1106 primary tumours and 187 metastatic lesions. Claudin-6 expression was scored according to the Gastric criteria and correlated with clinicopathological characteristics and follow-up data. Claudin-6 expression was detected in 18% of ECs and was highly expressed in 10% of all samples. High expression was observed in 49% of serous tumours and 22% of carcinosarcomas. High Claudin-6 independently predicted poor disease-specific survival in multivariate analysis (HR: 1.7, CI: 1.2-2.4, p = 0.002). In the paired primary-metastasis cohort, Claudin-6 was highly expressed in 19% of primary tumours and, of these, 77% maintained high expression in at least one corresponding metastatic lesion. Our study identified Claudin-6 as an independent prognostic marker in EC and as a potential target for ADCs, particularly in serous and carcinosarcoma subtypes.

Approximately 80% of deaths from ovarian cancer are due to high-grade serous carcinoma (HGSC), which has the highest proportion of BRCA1 or BRCA2 (BRCA1/BRCA2) mutations of any cancer type and is a highly chromosomally unstable disease. Despite the introduction of targeted therapies benefitting some patients with HGSC as well as surgical advances, only 50% of patients will survive more than 5 years, and just 30% of patients who present with advanced disease without BRCA1/BRCA2 mutations will survive this long. This Expert Recommendation is based on discussions among emerging and leading ovarian cancer researchers at the 15th Helene Harris Memorial Trust International Forum on ovarian cancer hosted by Ovarian Cancer Action in October 2024. The meeting considered advances in HGSC research and treatment made over the last decade, current challenges, emerging technologies in prevention, early detection, and treatment, and research priorities for the years ahead.

Objective: To determine the frequency and clinicopathological features of incidental premalignant and malignant gynecological lesions detected after hysterectomies performed for benign indications, and to identify associated risk factors. Methodology: This retrospective study reviewed 1,047 hysterectomies performed for benign conditions at a tertiary center in Ankara, Turkiye, over a ten years period (January 2006-December 2015). Demographic characteristics, preoperative assessments, surgical indications, and histopathological outcomes were analyzed. Incidental lesions were defined as pre-malignant or malignant pathologies identified postoperatively without prior clinical suspicion. Statistical analyses were performed using chi-square and t-tests. Results: Incidental pre-malignant or malignant lesions were identified in 6% (n=63) of cases, including cervical dysplasia/HSIL (0.9%), borderline ovarian tumors (1.1%), endometrial adenocarcinoma (0.5%), leiomyosarcoma (0.5%), and high-grade serous ovarian carcinoma (0.6%). Postmenopausal women had a significantly higher incidence than premenopausal women (9.2% vs. 3.8%, p<0.001). Patients with incidental findings were older than those with benign pathology (55.4 ± 11.2 vs. 52.7 ± 9.6 years, p=0.034). Larger myomas were associated with uterine sarcoma (172 ± 92 mm vs. 71 ± 39 mm, p<0.001). Ovarian malignancies were detected in 2.4% of cases without suspicious ultrasound features and in 14.8% of cases with ≥2 malignancy criteria (p=0.013). Serous tubal intraepithelial carcinoma (STIC) was identified in 0.28% (n=3). Conclusion: Incidental pre-malignant or malignant lesions were present in 6% of hysterectomies performed for benign indications. Age, menopausal status, myoma size, and suspicious imaging features were significant predictors. Preoperative evaluation may not completely exclude the possibility of occult pathology; therefore, this risk should be discussed during preoperative counseling.

This study reports a rare case of mixed ovarian carcinoma composed of squamous cell carcinoma (SCC) and high-grade serous carcinoma (HGSC) arising from endometriosis, and provides a systematic review of the relevant literature. A 59-year-old female presented with bilateral ovarian cystic lesions (4.6cm on the left, 9.6cm on the right) and a mural nodule in the right ovarian cyst. Serum tumor markers were CA125 57.50 U/mL and CA19-9 6.74 U/mL. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and appendectomy. Histopathological examination revealed a mixed carcinoma of the right ovary composed of SCC and HGSC, with adjacent serous borderline tumor and endometriotic cyst. The left ovary showed a serous borderline tumor with endometriosis. Next-generation sequencing (NGS) identified two distinct TP53 mutations: a missense mutation in the HGSC component and a splice-site mutation in the SCC component. The patient received six cycles of paclitaxel and carboplatin chemotherapy. Within two months after completing the treatment, tumor markers had normalized and no recurrence was detected. We describe a 59-year-old woman diagnosed with stage IA mixed ovarian carcinoma (SCC and HGSC), in which two distinct TP53 gene mutations were identified. A systematic literature review was conducted using PubMed, Embase, and Web of Science databases. A total of eight published cases of ovarian mixed carcinoma containing a squamous component were identified. Of these, five originated from endometriosis and one from a mature cystic teratoma. Histologically, five cases were endometrioid adenocarcinoma with squamous differentiation, while others included clear cell carcinoma, mucoepidermoid carcinoma, and HGSC (the present case), each admixed with SCC components. This is the first reported case of ovarian HGSC coexisting with SCC. Given its extreme rarity, standardized treatment strategies have not yet been established.

This study evaluated the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system in Chinese uterine serous carcinoma (USC) patients and defined the disease's molecular landscape. Retrospective analysis classified USC patients by both 2009 and 2023 FIGO systems; staging migration was analyzed via cross-tabulation and Sankey diagrams. Molecular classification used the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) algorithm, with human epidermal growth factor receptor 2 (HER2) expression assessed by immunohistochemistry (IHC). Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and log-rank tests; the 2023 system's prognostic ability was validated via time-dependent receiver operating characteristic (ROC) curves, Harrell's C-index, and Akaike's Information Criterion (AIC). The 2023 system induced significant staging migration, mainly from IA/IB to IC (endometrium-confined tumors) or IIC (myometrial invasion). This reclassification achieved better prognostic stratification, shown by higher C-index and lower AIC than the 2009 system. Molecular profiling clarified subtype distribution, and HER2 overexpression was confirmed in substantial subsets, highlighting therapeutic relevance. The 2023 FIGO staging system provides superior prognostic stratification for Chinese USC patients compared to the 2009 version.

Folate receptor 1 (FOLR1) has recently become a well-accepted therapeutic target in advanced-stage cancers. In this study, the prevalence of FOLR1 expression across all types of gynecologic tumors was investigated and correlated with selected clinicopathologic features. A total of 306 gynecologic tumors from 304 patients were evaluated for FOLR1 expression by immunohistochemistry (IHC). A positive FOLR1 is defined as ≥75% of viable tumor cells with moderate to strong membrane staining. Of 306 tumors, 31 (10.1%) had positive FOLR1 tests; a large majority of these FOLR1-positive tumors were HGSCs (64.5%), followed by uterine serous carcinoma, poorly differentiated/high-grade carcinoma, ovarian endometrioid carcinoma, ovarian mixed carcinoma, ovarian low-grade serous carcinoma, and serous borderline tumor with cribriform and micropapillary features. FOLR1 overexpression correlated with positive PD-L1 expression (P=0.012), intact mismatch repair protein (MMR) expression (P=0.024), and positive ER expression (P=0.040). In endometrial tumors, positive FOLR1 expression was associated with poor histologic grade (P=0.019), larger tumor size (P=0.048), mutant p53 expression (P<0.001), and lower PR expression (P=0.015). Endometrial tumors with FOLR1 overexpression had a significantly higher rate of TP53 mutations (P=0.013), while all endometrial tumors with PTEN alterations were negative for FOLR1 (P=0.037). Overall, FOLR1 overexpression was associated with poor prognostic factors, such as advanced clinical stage, increased recurrence rate, higher pathologic T and N stage, poor histologic grade, larger tumor size, lymphovascular invasion, uterine serosa involvement, and shorter progression-free survival.

The current classification of ovarian seromucinous tumors is somewhat complex and may present challenges in routine diagnostic practice. In the fifth edition of the WHO classification, seromucinous carcinoma (SMC) is generally regarded as a subtype of endometrioid carcinoma (EC) because of its limited diagnostic reproducibility and evidence that most tumors meeting the morphologic criteria for SMC can be reassigned to EC or low-grade serous carcinoma (LGSC) with mucinous differentiation based on integrated morphologic, immunophenotypic, and genotypic analyses. However, SMC-like tumors reassigned to LGSC remain unaddressed in the current classification systems. Although seromucinous borderline tumor (SMBT) is generally regarded as a reproducible entity, diagnostic difficulties may arise in certain cases. We report the case of an 80-yr-old woman with a large multicystic ovarian tumor predominantly composed of serous cells with micropapillary architecture characteristic of a serous borderline tumor (SBT), admixed with Müllerian-type mucinous cells. The serous component showed diffuse and strong WT1 positivity, whereas the mucinous cells exhibited variable WT1 expression. Under the current WHO classification, this tumor is diagnosed as an SMBT because it fulfills the morphology-based criteria. However, the predominance of the serous component showing diffuse WT1 expression is unusual for this entity and raises the possibility that the tumor represents SBT with mucinous differentiation, a potential borderline malignant counterpart of LGSC with mucinous differentiation. This case suggests a potential diagnostic overlap between SMBT and SBT, underscoring the need for further accumulation of similar cases and integrated analyses to clarify whether such tumors may warrant distinction from typical SMBT.

Kinesin family member 15 (KIF15) is a molecular motor protein that participates in bipolar spindle assembly and centrosome separation during metaphase in normal cells. However, accumulating evidence has shown that KIF15 is aberrantly regulated in the state of malignancy and is associated with the progression of cancers. We analyzed the mRNA expression, protein expression, single-cell gene expression, prognoses, and immune reactivities of KIF15 using the data from various sources, including the Cancer Cell Line Encyclopedia, The Cancer Genome Atlas database, the Clinical Proteomic Tumor Analysis Consortium Confirmatory/Discovery database, and Cancer Single-cell Expression Map. Additionally, immunohistochemistry was performed to validate KIF15 protein expression in human tumor samples. The data from the present pan-cancer analysis elucidated that KIF15 expression was increased in more than 25 human tumors. Furthermore, it was found to be highly corre-lated with biological pathways, immune cell infiltration, and poor prognoses across multiple cancers. Additionally, tissue microarray analysis confirmed abundant cytoplasmic KIF15 expression in ovarian serous carcinoma and colorectal adenocarcinoma, with significantly higher levels compared to adjacent normal tissues. Consistent patterns of high KIF15 expression were also evident across various cancer cell lines in the CCLE dataset. Collectively, these observations suggest KIF15 is in-timately involved in the progression of multiple human cancers. By analyzing both the pro-teins that interact with KIF15 and the genes that show correlation with its expression, KEGG pathway enrichment indicated that processes such as cell cycle regulation, gap and tight junction dynamics, involvement of microRNAs in cancer, and the p53 signaling pathway may underlie the role of KIF15 in cancer development. KIF15 may serve as a potential biomarker and oncogenic factor in multiple cancer types.