Background Kinesin family member 20A (KIF20A), a microtubule-dependent motor protein of the Kinesin superfamily, is involved in cell division and organelle transport. Its expression is dysregulated in various cancers and is closely related to tumor metastasis and patient prognosis. However, its specific functions in different tumor types and the potential as an anticancer target have not been fully elucidated, and a systematic pan-cancer analysis is lacking. Methods This study integrated multiple cancer database resources and systematically analyzed the multi-omics alterations of KIF20A in different cancers using R software, including gene expression, genomic variation, methylation status, biological pathways, and clinical value. In addition, we evaluated the regulatory role and immunotherapy potential of KIF20A in the tumor microenvironment through various bioinformatics algorithms. Finally, we explored the impact of KIF20A on the biological behaviors of Kidney Renal Clear Cell Carcinoma (KIRC) cells through in vitro and in vivo experiments. Results KIF20A is localized in the nucleus and participates in the cell cycle process, serving as a core gene for tumor cell growth. It undergoes copy number alterations in various tumors, and its high expression is closely associated with clinical progression, poor prognosis, and activation of classical oncogenic pathways in multiple cancers. Mechanistically, aberrant epigenetic modifications and mutations in hallmark pathways are significant reasons for the dysregulated expression of KIF20A. Furthermore, the expression of KIF20A correlates with immune cell infiltration and the expression of immune checkpoint molecules, impacting the efficacy of immunotherapy in various cancers. In vitro experiments have confirmed that interfering with KIF20A expression can effectively inhibit the proliferation, migration, and invasion of KIRC cells. Furthermore, in vivo experimental results indicate that interfering with KIF20A can inhibit tumor growth in nude mice. Conclusion To our knowledge, this is the first study to reveal the role of KIF20A in tumorigenesis and development from a pan-cancer multi-omics perspective, providing solid theoretical and experimental evidence for KIF20A as a potential anti-cancer therapeutic target.

Penile squamous cell carcinomas (pSCC) are broadly divided into two subgroups based on their etiopathogenesis: Human Papillomavirus (HPV)-associated and HPV-independent. HPV-associated pSCC is driven by high-risk HPV and commonly overexpresses p16 by immunohistochemistry (IHC), making it a widely used surrogate for HPV presence. HPV-associated pSCC encompasses multiple histologic subtypes, including basaloid, warty, mixed (warty-basaloid), clear cell, lymphoepithelioma-like, and medullary carcinomas. Although most of these have a distinct morphology, a "block" or "diffuse" staining pattern of p16 IHC is recommended for categorically classifying them as HPV-associated pSCC. Molecular diagnostics (e.g., HPV DNA or RNA assays) are rarely employed for the classification of pSCC. The prognostic relevance of HPV status and p16 overexpression remains under investigation, but preliminary findings suggest that HPV-associated / p16-positive tumors may have a more favorable prognosis, with better survival outcomes, and may also dictate the choice of therapy in advanced cases. Larger multicentric datasets from regions of higher incidence, harmonized criteria for p16 IHC interpretation, and standardized HPV detection methods are needed to further understand the utility of these biomarkers in pSCC. Finally, the relevance and impact of HPV vaccination on HPV-associated pSCC are not well documented, largely because male vaccination is not yet accepted globally.

Papillary renal neoplasm with reverse polarity (PRNRP) is a new pathological type of renal tumor, and its incidence is low. It is considered to be an indolent renal tumor at present. It is rare for PRNRP to co-occur with other tumors in the same kidney. Like other renal tumors, patients with PRNRP do not have any specific clinical manifestations. During surgery, we resected a solid and a cystic lesion in the left kidney simultaneously, and performed two partial nephrectomy on the ipsilateral kidney at one time, both with good surgical results. The postoperative pathological results were as follows: (1) solid lesions are PRNRP, and (2) cystic lesions are RCCC. Here, we present a case of PRNRP concurrent with RCCC and review the literature.

Pembrolizumab plus lenvatinib in recurrent gynaecological clear cell carcinoma (LARA): a multicentre, single-arm, phase 2 trial.

To investigate the differences fluorodeoxyglucose (FDG) dynamics between clear cell renal cell carcinoma (ccRCC) and non-ccRCC as a potential diagnostic clue, using dynamic whole-body (D-WB) and dual-time-point (DTP) FDG-PET/computed tomography (CT) imaging. D-WB and DTP FDG-PET/CT scans were performed for 26 RCC patients. We obtained Pearson's correlation coefficients between the static [maximum standardized uptake value (SUVmax) and tumor size] and dynamic [metabolic rate (MRFDG) and distribution volume of FDG (DVFDG)] parameters. We compared MRFDG and DVFDG by tumor type and performed receiver operating characteristic (ROC) analyses for each parameter. Nineteen ccRCC and nine non-ccRCC lesions including molecularly defined carcinomas were analyzed. Compared with the ccRCC (r = 0.55-0.81), the MRFDG in the non-ccRCC was more strongly correlated with the early (SUVe) and delayed (SUVd) SUVmax and tumor size (r = 0.72-0.97). The DVFDG in the non-ccRCC was more strongly correlated with SUVe and SUVd (r = 0.93, 0.84) vs. the ccRCC (r = 0.55, 0.66). SUVe and SUVd were significantly higher in the non-ccRCC vs. ccRCC (analyses for all or T3/4 RCC, both P < 0.05). MRFDG was significantly higher in the T3/4 non-ccRCC vs. the T3/4 ccRCC (P = 0.04). In the ROC analysis for differentiating ccRCC and non-ccRCC, SUVd showed the highest area under the curve (0.92-0.93 for all and T3/4 RCC) than other parameters (0.70-0.84). D-WB FDG-PET/CT imaging clearly demonstrated different FDG dynamics between ccRCC and non-ccRCC. Non-ccRCC showed higher MRFDG values than ccRCC, but dynamic images have a limited role in differentiating these lesions. SUVd could be the most suitable parameter for differentiating ccRCC and non-ccRCC.

Dysregulation of atrazine-associated core gene networks and risk prediction in human cancers: Insights from integrated transcriptomics and network toxicology analyses.

Transcriptomic landscape of coexisting ovarian clear cell carcinoma and endometriosis: Insights into malignant transformation.

Despite curative surgery and adjuvant chemotherapy, a significant number of early stage I to II ovarian cancers relapse. The CA125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor intrinsic chemosensitivity in advanced epithelial ovarian cancer. We assessed the prognostic value of KELIM in patients with early-stage ovarian cancer, with respect to 5-year recurrence-free survival and overall survival, using the Meta-Analysis in Ovarian Cancer, which is the Gynecologic Cancer InterGroup individual patient-data meta-analysis of randomized trials evaluating different adjuvant chemotherapy regimens. Individual patient KELIM values were previously estimated in 5884 patients from the Meta-Analysis in Ovarian Cancer. The prognostic value of KELIM was assessed using univariable & multivariable analyses in patients with resected International Federation of Gynecology and Obstetrics stage I and II disease. Overall, 1143 patients were identified, including clear cell (46.7%); serous (23.7%); endometrioid (12.4%); and mucinous carcinomas (3.9%). In multivariable analyses, a favorable KELIM score (≥1.0) was associated with higher 5-year recurrence-free survival (68.3% vs 55.9%; HR 0.61, 95% CI 0.48 to 0.77) and 5-year overall survival (80.7% vs 72.8%; HR 0.50, 95% CI 0.36 to 0.68), as was the histological sub-type. In exploratory analyses, KELIM score was a prognostic factor regarding 5-year recurrence-free survival and overall survival across all sub-types (especially clear cell carcinoma and serous, with HR ranging from 0.45 to 0.63) with baseline CA125 ≥15 IU/L, except for mucinous histology. The pragmatic KELIM score is an independent prognostic factor in patients with a non-mucinous stage I to II ovarian cancer optimally resected and treated with adjuvant chemotherapy. KELIM may help identify the patients at higher risk of relapse and death requiring closer follow-up or treatment intensification.

Sentinel lymph node mapping versus systemic lymphadenectomy in high-risk endometrial cancer patients: A meta-analysis of oncologic outcomes.

HER2 immunoreactivity in advanced non-p53abn endometrial carcinoma: Association with clinical features, prognosis, and molecular characteristics.

Metabolic vulnerabilities in ovarian cancer decoding the nexus between nutrient adaptation and therapy resistance.

Postoperative radiation therapy in women with FIGO stage I clear cell and papillary serous carcinomas of the uterus: an analysis of the SEER database

Background: Systemic inflammation and nutritional status are key determinants of prognosis in metastatic clear-cell renal carcinoma (mccRCC). Composite indices such as the Systemic Immune–Inflammation Index (SII) and the Modified Glasgow Prognostic Score (mGPS) have demonstrated prognostic relevance across cancers, but real-world data in mccRCC remain limited. Methods: This retrospective, single-center cohort included patients with histologically confirmed mccRCC who received first-line tyrosine kinase inhibitor (TKI) monotherapy (sunitinib, pazopanib, or cabozantinib) between November 2022 and November 2024 at Etlik City Hospital (Ankara, Türkiye). Associations between inflammatory–nutritional indices (SII, mGPS) and progression-free survival (PFS) were evaluated using Kaplan–Meier and multivariable logistic regression analyses. Results: A total of 55 patients met eligibility criteria and were included in the analysis. The median age was 62 years (IQR 52–71), and 67% were male. Median PFS was 13.24 months (95% CI 7.75–19.12), while median OS was not reached. High SII (≥ 870) was independently associated with shorter PFS in multivariable analysis (OR 5.05; 95% CI 1.14–15.77; p = 0.039). mGPS (1–2) was significantly associated with inferior PFS in Kaplan–Meier analysis (HR 3.43; 95% CI 1.42–8.30; p = 0.006; log-rank p = 0.001), but lost significance in multivariable modeling. Metformin use (OR 0.12; 95% CI 0.02–0.93; p = 0.044), sunitinib therapy (OR 0.07; 95% CI 0.006–0.74; p = 0.027), and favorable/intermediate IMDC risk group (OR 0.17; 95% CI 0.06–0.96; p = 0.047) were independently associated with a lower progression risk. Patients treated with cabozantinib (n = 15) showed a numerically longer median PFS (18.6 months; 95% CI 13.8–23.3) compared with sunitinib (n = 25, 12.2 months; 95% CI 5.5–19.0) and pazopanib (n = 15, 12.1 months; 95% CI 6.7–17.5), although this difference was not statistically significant (log-rank p = 0.152). Conclusion: In this real-world cohort of patients with mccRCC treated with first-line TKI, host-related inflammatory and nutritional status were closely associated with progression-free survival. Additionally, patients classified within the favorable IMDC risk group exhibited a significantly lower risk of progression, highlighting the importance of integrating clinical risk stratification with systemic inflammatory and nutritional markers. Incorporating such easily measurable biomarkers and clinical risk scores into existing prognostic models may enhance individualized risk assessment and therapeutic decision-making. Future prospective, multicenter, randomized controlled, and artificial intelligence–assisted studies are warranted to validate these findings and refine precision oncology approaches in this population.

Comprehensive analysis and experimental confirmation identify ADRM1 plays an oncogenic and immunosuppression role in KIRC.

Diagnosis and treatment of primary clear cell carcinoma of the female urethra

Possible overestimation of treatment effects of pelvic and para-aortic lymphadenectomy for early-stage ovarian clear cell carcinoma: a retrospective propensity-score weighted multi-center cohort study

Clear cell carcinoma arising in the background of atypical polypoid adenomyoma

ObjectiveThis investigation aimed to assess the applicability of fertility-sparing surgery (FSS) for early-stage ovarian clear cell carcinoma (OCCC) while examining the clinical requirements for lymph node dissection and adjuvant chemotherapy.SubjectsA total of 849 stage I patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were evaluated through Kaplan–Meier methodology for both overall survival (OS) and disease-specific survival (DSS). Prognostic determinants were examined using multivariate regression modeling.ResultsAmong the 849 patients, 84.3% (716 cases) underwent hysterectomy, and 15.7% (133 cases) received FSS. No significant difference was found in OS (90.6% vs. 87.2%, P = 0.257) or DSS (91.6% vs. 87.7%, P = 0.302) between FSS and hysterectomy cohort. Tumor diameter > 10 cm, stage IC and lymphadenectomy were independent prognostic factors for patients with stage I OCCC. Among patients with a tumor diameter ≤ 10 cm, those who underwent FSS had better OS (97.9% vs. 88.3%, P = 0.034) and DSS (97.9% vs. 88.3%, P = 0.044) than those who received hysterectomy. In stage IA patients, there were no significant differences in prognosis between the two operations. Neither lymphadenectomy nor chemotherapy did not demonstrate superior prognosis in the FSS cohort, whereas chemotherapy was associated with inferior OS (93.5% vs. 84.9%, P = 0.007) and DSS (93.5% vs. 85.5%, P = 0.007) in the hysterectomy cohort.ConclusionFor patients with stage IC OCCC and a tumor diameter > 10 cm, the selection of FSS should be approached with caution. Given the limitations of the SEER database, larger-scale prospective cohort studies are required to validate the influence of lymphadenectomy and postoperative adjuvant chemotherapy on the prognosis of patients undergoing FSS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00404-026-08310-9.

Squamous differentiation in head and neck tumors is so common that we sometimes don't think about the diversity of lesions that can show it and how to tease them apart. Accurate molecular subclassification of squamous tumors now directly informs patient diagnosis, prognosis, and treatment. Viral-associated carcinomas remain the largest and most clinically important type. Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) and Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma are defined by distinct oncogenic mechanisms, morphologic features, and clinical behavior, with routine use of p16 and EBER in situ hybridization now standard practice. Testing for viral association also aids in the work-up of metastatic squamous carcinoma of unknown primary. Translocation-associated carcinomas, once considered a non-sequitur, are now recognized as clinically distinct entities in head and neck pathology. DEK::AFF2 fusion nonkeratinizing SCC is typically a papillary sinonasal tumor with deceptively bland morphology while NUT carcinoma represents the opposite extreme, presenting as an aggressive, often midline, poorly differentiated carcinoma, a small subset of which can even be cytokeratin negative. Both can be diagnosed by fluorescence in situ hybridization (FISH) or by fusion specific immunohistochemistry. Finally, hyalinizing clear cell carcinoma (HCCC) is a bland, nested oral cavity and pharyngeal submucosal tumor with squamous immunophenotype and illustrates how EWSR1 fusions blur the boundaries between squamous and salivary neoplasms, with ancillary FISH sometimes needed to confirm the diagnosis. Viral and targeted molecular testing are critical to classification of these tumors. "So it's squamous" is no longer the end of the work up-it is the beginning of a more refined classification.

The identification of novel, molecularly defined neoplasms continue to refine diagnostic precision and illuminate tumor pathogenesis. Assessment of the EWSR1 locus has emerged as a frequently utilized diagnostic tool in the work-up of salivary and craniofacial bone tumors, due to its established perturbations in hyalinizing clear cell carcinomas, myoepithelial carcinomas, rare mucoepidermoid carcinomas, and others. Here, we report a case of a 12-year-old female who presented with a large expansile intraosseous lesion within the left body of the mandible, initially biopsied with negative FISH results for EWSR1, but RNA-sequencing identified an EWSR1::YY1 rearrangement. The subsequent resection is presented here and shows an epithelial immunophenotype tumor without myoepithelial differentiation. To the best of our knowledge, this represents a novel epithelial tumor harboring an EWSR1::YY1 fusion outside the peritoneal/visceral cavity. The EWSR1::YY1 fusion is a recently described genetic event, initially reported in epithelioid peritoneal mesothelioma, and represents the first direct oncogenic involvement of the transcription factor YY1.