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[Bromocriptine and prostatic carcinoma: testosterone metabolism in relation to tumor grading (author's transl)].

Since Prolactin has intra- and extrapostatic effects on growth and function of the prostate, the influence of the anti-prolactin bromocriptine (PRAVIDEL) was investigated in 15 patients with untreated prostatic carcinoma of various grades of differentiation in vivo. A five-days treatment with 15 mg Pravidel daily significantly suppressed prostatic androgen uptake, unrelated to tumor grading. 5 alpha-Reductase was favored in poorly differentiated lesions with a decreased testosterone/dihydrotestosterone ratio. The pretherapeutic accumulation of 5 alpha-androstanediol was diminished after Pravidel and the tissue/plasma ratio decreased. The 17 beta-hydroxy-pathway of testosterone is predominant as compared to the 17-keto pathway; both pathways are favored after Pravidel in poorly differentiated tumors. Intraprostatic metabolic effects of Pravidel are not related to peripheral androgen levels nor are they dependent on altered prostatic hormone uptake. In the poorly differentiated prostatic tumors Pravidel initiates a metabolic situation as observed in prostate cancer responding to androgen depletion or estrogen therapy.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Diffusion MRI radiomics in meningiomas: imaging correlates of tumor grade and intraoperative consistency.

OBJECTIVE: Despite advancements in imaging studies, the preoperative prediction of the biological behavior and intraoperative consistency of intracranial meningiomas remains limited. This study evaluated the association of volumetric diffusion-based and texture-derived radiomic features extracted from routine MRI with histopathological aggressiveness and intraoperative tumor consistency. METHODS: Ninety-seven intracranial meningiomas resected at two tertiary centers were retrospectively analyzed. Volumetric segmentation was performed on contrast-enhanced T1-weighted MRI and coregistered to apparent diffusion coefficient (ADC) maps. Data on first-order diffusion metrics and selected texture features were collected. The associations between World Health Organization (WHO) grade and Ki-67 index were assessed using nonparametric tests and Spearman correlation analysis. Independent factors associated with intraoperative tumor consistency (Zada grades 1-5) were evaluated via multivariate ordinal logistic regression analysis that adjusted for tumor volume, skull base location, calcification status, and WHO grade. Secondary receiver operating characteristic (ROC) curve analyses were performed to differentiate solid (Zada grades 4-5) from soft (Zada grades 1-2) tumors. ROC analyses were performed within the study cohort and were intended as exploratory assessments of discriminative performance. RESULTS: The mean ADC (ADCmean) and the 10th percentile of the ADC decreased significantly with increasing WHO grade (p < 0.001). ADCmean had a moderate inverse correlation with the Ki-67 index (r = -0.42, p < 0.001) and intraoperative tumor consistency (r = -0.45, p < 0.001). In the multivariate analysis, the ADCmean remained independently associated with increasing tumor firmness. Each 0.1 &#xd7; 10-3 mm2/sec increase corresponded to a 38% reduction in the odds of belonging to a higher consistency category (OR 0.62, 95% CI 0.51-0.74, p < 0.001). The ROC analysis showed good discrimination for solid tumors (area under the curve 0.847, 95% CI 0.742-0.953) and soft tumors (area under the curve 0.824, 95% CI 0.714-0.935). Texture features had weaker associations with intraoperative tumor consistency. CONCLUSIONS: Volumetric diffusion-derived metrics, particularly ADCmean, are associated with both histopathological aggressiveness and intraoperative tumor firmness in meningiomas. Diffusion imaging may reflect a graded microstructural continuum rather than a purely dichotomous property, providing complementary preoperative insights into surgical complexity.

Humans

Ploidy and proliferation in human bladder tumors as measured by flow-cytofluorometric DNA-analysis and its relations to histopathology and cytology.

Biopsies from bladder tumors of 41 patients were investigated by flow-cytofluorometric DNA analysis and compared with exfoliated cells. The degrees of ploidy and proliferation were determined. Good agreement was found between the degrees of ploidy and proliferation in the biopsies and the exfoliated cell material. Tumors Grade I-II were either euploid or aneuploid. All Grade III tumors were aneuploid. The S-phase fractions were about 6% in the diploid tumors and 17% with large variations in the aneuploid tumors. The histological grading was well correlated to the number of S-phase cells and the occurrence of aneuploidy. When the Grade II tumors were divided into two groups having lesser and more pronounced atypia, the two groups differed significantly with regard to their degrees of proliferation. In addition to aneuploidy as an important criterium for malignancy, the degree of proliferation appears to be of major biological significance.

Aneuploidy

Long-term epidemiological trends in (primary) pediatric central nervous system tumors: a 25-year cohort analysis in Western Mexico.

BACKGROUND: Central nervous system tumors (CNSTs) represent a significant oncological challenge in pediatric populations, particularly in developing regions where access to diagnostic and therapeutic resources is limited. METHODS: This research investigates the epidemiology, histological classifications, and survival outcomes of CNST in a cohort of pediatric patients aged 0 to 19&#xa0;years within a 25-year retrospective study at the Civil Hospital of Guadalajara, Mexico, from 1999 to 2024. RESULTS: Data was analyzed from 273 patients who met inclusion criteria, revealing a higher incidence in males (51.6%) with a mean age at diagnosis of 8.2&#xa0;years. Histological analysis revealed gliomas as the most common type (52.7%), followed by embryonal tumors (28.6%). High-grade tumors (WHO grade 4) comprised 49.8% of cases, demonstrating significantly poorer survival outcomes (median overall survival of 13.5&#xa0;months) compared to lower-grade tumors (up to 57&#xa0;months). The predominance of tumors in the supratentorial region and the notable differences in survival outcomes by tumor type underscore the varied impact of geographical and socioeconomic factors on pediatric oncology in Mexico. CONCLUSION: This study highlights the critical need for improved healthcare infrastructure and early diagnosis initiatives, as well as the importance of targeted research to address disparities in treatment and outcomes for pediatric CNST in this region.

Humans

Spinal meningiomas: histopathological grading using a benchmark radiomics model with notes on disease control.

OBJECTIVE: Spinal meningiomas (SMs) are common primary spinal tumors for which surgery is considered the first-line treatment when safe and feasible. The ability to extrapolate the tumor grade from preoperative imaging may significantly inform early patient expectation-setting regarding recurrence. Building on radiomics studies in cranial meningiomas, the authors aimed to construct a benchmark radiomics model to preoperatively identify the histological grade of SMs. METHODS: Institutional surgical records from May 2012 to November 2025 were queried for pathology-confirmed meningiomas below the foramen magnum, with preoperative contrast-enhanced imaging available for segmentation. SMs were classified as low-grade (WHO grade 1) and high-grade (WHO grade 2 tumors and grade 1 tumors with atypia). Tumors were manually segmented, and features were extracted using the PyRadiomics software package. An ensemble model of k-nearest neighbors, random forest, and support vector machine classifiers was trained using nested cross-validation on a subset of 10 features to differentiate tumor grades. Clinical data for the cohort were also extracted, and disease control in an adjunctive clinical series was assessed. RESULTS: Seventy-four patients were included in radiomics analysis, with an area under the receiver operating characteristic curve of 0.879 and a mean F1 score of 0.748. The model's top 5 features were all texture features that differed significantly (p < 0.05) across low- and high-grade SMs. These included measures of tumor textural and contrast-enhancement heterogeneity, with overlap with features reported in radiomics models for histological grading of intracranial meningiomas. Fifty-five patients with a median radiographic follow-up of 22.2 (range 1.9-86.4) months remained for clinical analysis after exclusion of patients with less than 1 month of follow-up and syndromic meningiomas. Four recurrences occurred at a median of 20.8 (range 1.8-41.8) months. High-grade tumor pathology did not significantly impact progression-free survival (p = 0.682, log-rank test; Cox regression high vs low grade hazard ratio [HR] 0.62, 95% CI 0.06-6.11, p = 0.685). Subtotal resection was associated with poorer progression-free survival than gross-total resection (p = 0.004, log-rank test; Cox regression subtotal vs gross-total resection HR 10.62, 95% CI 1.46-77.05, p = 0.019). These findings remain contextualized within a relatively limited follow-up window and small recurrence event count, suggesting a need to characterize the interplay between tumor grade and extent of resection as drivers of local disease control in SMs. CONCLUSIONS: A preoperative radiomics model can stratify high-grade SMs using open-source tools applied to single-institution data.

Humans

The management of clinical stage I endometrial carcinoma.

A retrospective analyses of 307 cases with clinical Stage I endometrial carcinoma was done in an attempt to determine the role of radiation therapy in the optimal treatment of this disease. A review of the modern literature with over 9000 cases served as a useful tool to corroborate inferences and conclusions. The present series has 155 patients (51%) treated with preoperative megavoltage external pelvic radiation with a variation in doses of less than 6%. Five-year survival estimates (79%-83%) in clinical Stage I endometrial carcinoma are similar among the several main treatment combination that are employed; they become a useless parameter for any comparison. The pelvic failure rate constitutes a more useful guideline in assessing the most adequate therapy. The pathologic grade of the tumor is the main prognosticator in endometrial carcinoma. Intimately related to the tumor grade is the depth of myometrial invasion of the carcinoma. The size of the uterus and/or its cavity carry less prognostic significance than traditionally thought. For grade I lesions, there is little error in diagnosis, few pelvic failures and excellent survival (96%); they could be approached with initial surgery and postoperative radiation reserved for selected patients. For grade 2 tumors, the error in diagnosis and the failure rate increases with an overall survival of 87%. For grade 3 tumors, the error in diagnosis and failure rates are quite high with a 5 year survival of only 70%. Preoperative radiation, especially external beam therapy, is suggested for grades 2 and 3 Stage I tumors. The use of this treatment modality yields only 3% pelvic failure and an overall 5 year survival of almost 90%.

Carcinoma

Mucoepidermoid carcinoma of the bronchus: an electron microscopic study of the low grade and the high grade variants.

Two cases of mucoepidermoid carcinoma of the bronchus--one a low grade tumor and the other a high grade tumor--are presented with findings by light and electron microscopy. This represents the first report of the ultrastructure of mucoepidermoid carcinoma of the bronchus and demonstrates the ultrastructural similarities between the low grade exophytic tumor confined to the bronchus and the high grade infiltrating tumor with lymph node and pulmonary metastases. The ultrastructural features are similar to those described for mucoepidermoid carcinoma of the salivary gland and are consistent with the proposed origin of the tumor from the submucosal bronchial gland duct. These two cases and a review of previously reported cases indicate that, analogous to mucoepidermoid carcinoma of the salivary glands, mucoepidermoid carcinoma of the bronchus may occur as either a low grade or high grade variant which can be identified on the basis of growth characteristics and histologic features.

Adult

Spatial analysis reveals the evolving organization of IDH-mutant glioma.

Adult diffuse gliomas are composed of malignant cell states interwoven with the non-malignant brain microenvironment. Here, we combine spatial transcriptomics and spatial proteomics of isocitrate dehydrogenase (IDH)-mutant gliomas to define organizational principles across histological grades. In low-grade tumors, spatial organization is shaped by underlying brain anatomy. We identify a functional white-gray matter junction that restricts cortical invasion and is associated with marked changes in tumor composition and cellular phenotypes. This junction is preferentially traversed by oligodendrocyte progenitor (OPC)-like malignant cells, suggesting a role in tumor expansion. In contrast, tumors with intermediate histological features are largely disorganized, with few recurring interactions between cancer cell states and microenvironmental cell types. In high-grade tumors, hypoxia-associated structure emerges, resembling IDH-wild-type glioblastoma. Together, these findings reveal two independent axes of spatial organization-from anatomy-driven structure in low-grade tumors to hypoxia-driven organization in high-grade tumors-and establish a framework linking tumor grade to recurrent spatial interactions.

Isocitrate Dehydrogenase

Spinal low-grade ependymal tumors harboring telomerase reverse transcriptase promoter mutation and chromosome 7 gain with methylation profile of spinal subependymoma.

Spinal intramedullary tumors comprise a heterogeneous group of entities with diverse histopathological features, making their diagnosis particularly challenging. With the introduction of DNA methylation profiling, the underlying biological diversity of these tumors has been increasingly clarified and systematized; however, owing to the rarity of these tumors, case accumulation remains limited, and significant challenges persist. In this study, we identified two cases of spinal ependymal tumors exhibiting a methylation profile of spinal (SP-) subependymoma (SEPN). Both cases occurred in elderly patients and demonstrated circumscribed growth consistent with low-grade ependymal tumors; however, these tumors did not exhibit the typical histopathological features required for a diagnosis of SEPN in the 2021 WHO classification of central nervous system (CNS) tumors, showing indistinct cluster formation, an astrocytic immunohistochemical profile suggested by Olig2 expression, and relatively elevated Ki-67 labeling indices of 4.5% and 3.1%. At the molecular level, both cases harbored telomerase reverse transcriptase promoter mutations and whole chromosome 7 gain. On two-dimensional t-distributed stochastic neighbor embedding analysis, both clustered within the SP-SEPN methylation class at its periphery, with low classifier calibration scores (0.70 and 0.69). According to the current WHO classification, these cases are designated as low-grade ependymal tumors (CNS WHO grade 2) with methylation profile of SP-SEPN because they do not meet the essential WHO histopathological criteria. Ependymal tumors exhibiting a methylation profile consistent with SEPN, but discordant histopathological features have been increasingly recognized, and the appropriate classification of such tumors remains a subject of ongoing debate. These cases provide important insights into the histopathological diversity of ependymal tumors and contribute to establishing a more comprehensive and systematic classification of ependymal tumors.

Aged

A prognostic study of urothelial renal pelvic tumors: comparison between the prognosis of patients treated with intrafascial nephrectomy and perifascial nephroureterectomy.

A comparison of the prognosis between 2 series of patients with urothelial renal pelvic tumors is presented. One series comprising 70 patients was operated with intrafascial nephrectomy with extirpation of varying length of the ureter. The other series comprising 38 patients was operated with transabdominal perifascial nephrectomy with homolateral adrenalectomy, total ureterectomy and in 28 patients retroperitoneal lymphadenectomy. The 5-year survival was 51% in the patients operated with intrafascial nephrectomy and 84% in the patients operated with perifascial nephrectomy. The difference in prognosis is statistically significant (p less than or equal to 0.01) and cannot be explained by differences in extent of tumor infiltration, tumor grade or tumor size. The main difference in prognosis between the two series was in patients with high stage tumors (Grabstald stage 3 and 4). The 5-year survival was 74% in patients with stage 3 and 4 tumors in the patients operated with perifascial nephrectomy compared with 37% in the patients operated with intrafascial nephrectomy. Since it is not possible with absolute certainty to determine tumor stage before the operation, an aggressive attitude against urothelial renal pelvic tumors is recommended. Thus the patients should undergo transabdominal perifascial nephroureterectomy including a cuff of the bladder wall and homolateral adrenalectomy. In patient with bilateral tumors, renal insufficiency of tumor in a single kidney parenchyma saving partial resection must be performed.

Adult

Biopsy of apparently normal urothelium in patients with bladder carcinoma.

We obtained 246 cold cup biopsies from pre-selected sites of apparently non-tumor-bearing bladder urothelium from 82 patients who presented with bladder cancer for the first time. Of 75 patients with transitional cell carcinoma 32 (43 per cent) suffered coincidental urothelial abnormalities, the most common being atypia. Significant abnormalities occurred more commonly (77 per cent) in association with high grade tumors than with low grade tumors (15 per cent).

Adenocarcinoma

Radiotherapy of intracranial astrocytomas: analysis of 417 cases treated from 1960 through 1969.

In a review of 417 intracranial astrocytomas treated radiotherapeutically at the Mayo Clinic from 1960 through 1969, the well-known correlation of tumor grade with survival was verified. Totally unexpected was the finding that age was fully as important a discriminant as tumor grade. Another unexpected finding was that patients treated with biopsy only followed by radiation therapy did as well as or slightly better than those subjected to resection followed by postoperative radiotherapy. We could not verify the importance to survival of either large dose or large volume radiotherapy, which has been emphasized by some. Patients receiving less than 1400 rets did just as well as or slightly better than those receiving more than 1400 rets. With low grade astrocytomas, survival beyond 4 years was significantly worse (higher death rates) in the group receiving more than 1400 rets. This suggested the possibility of radiation damage with delayed manifestations. We also could not verify an increased effectiveness for the generally accepted use of total brain irradiation for high grade gliomas.

Adolescent

Histologic grading of Wilms' tumor as potential prognostic factor: results of a retrospective study of 26 patients.

A histologic grading system based on tumor differentiation was applied in a retrospective study of 26 patients with Wilms' tumor to determine if it might provide an index to prognosis. The results were compared to those obtained by applying a histologic classification based on the presence or absence of individual histologic structures to the same tumors. Low grade tumors with predominance of differentiated structures--glomeruli and tubules--were associated with a better cure rate than high grade tumors composed mainly of undifferentiated spindle elements. The presence of undifferentiated large cells correlated with poor cure rate. The findings suggest that histologic grading may be valid as a prognostic factor in Wilms' tumor.

Adolescent

Inhibition of leukocyte migration by extracts of malignant prostatic tissue and correlation of degree of in vitro sensitization to clinical responsiveness in prostatic cancer patients.

In an attempt to evaluate the degree of in vitro cellular sensitization to tumor and its relationship to clinical responsiveness, direct leukocyte migration tests were carried out in patients with varying degrees of adenocarcinoma of the prostate employing pooled allogeneic extracts of normal, benign, and malignant prostatic tissue as a source of antigen. Cell-mediated immunity to presumably common prostatic tumor associated antigens was observed. The degree of sensitization of clinically significant specific reactivity of the patients' leukocytes to malignant prostatic tissue was greatest in patients with localized disease, low-grade tumor, and clinically inactive disease than in patients with advanced disease, high-grade tumor, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43 per cent) of 7 patients. Correlation in 4 patients was questionable because of observations of "stimulation" of migration rather than inhibition, suggested by some to be reflective of weak sensitization to tumor. Evaluation of a larger patient population as well as a prospective study of the relationship of the degree of sensitization and clinical responsiveness will be necessary before any definitive conclusions may be drawn regarding the present observations.

Adenocarcinoma

PLK1/FOXM1-associated tumor-cell state and macrophage-related immune features in endometrial cancer.

BACKGROUND: Polo-like kinase 1 (PLK1) and forkhead box M1 (FOXM1) have been widely studied in various cancers; however, their expression characteristics in endometrial cancer (EC) and their potential association with tumor microenvironment remodeling remain insufficiently characterized. METHODS: This study integrated The Cancer Genome Atlas uterine corpus endometrial carcinoma cohort, Gene Expression Omnibus, pan-cancer transcriptomic data, Human Protein Atlas/Clinical Proteomic Tumor Analysis Consortium, and local immunohistochemistry data to evaluate PLK1 expression and clinicopathological relevance across transcriptomic, proteomic, and histopathological data. Differential expression, survival, gene-set enrichment, transcription-factor enrichment, and immune-infiltration analyses characterized PLK1-associated features. In vitro experiments combined EC cell lines AN3CA and HEC-1A with co-immunoprecipitation, Western blotting, Transwell assays, and a THP-1 conditioned-medium model. Drug-response prediction and structure-based analysis prioritized candidate therapeutic hypotheses. RESULTS: PLK1 was consistently upregulated at both mRNA and protein levels in EC and was associated with higher tumor grade and International Federation of Gynecology and Obstetrics (FIGO) stage. In survival analysis, higher PLK1 expression was associated with poorer overall survival in univariable models but not after adjustment for age, tumor grade, and FIGO stage. Functional enrichment analysis showed that PLK1-associated genes were mainly involved in cell-cycle and mitotic processes. FOXM1 was identified as a potential candidate component of the PLK1-associated transcriptional program and was positively correlated with PLK1 expression and cell-cycle-related features. In vitro experiments supported an interaction between PLK1 and FOXM1 and suggested that FOXM1 Thr600 phosphorylation-related alterations were associated with migration and invasion phenotypes. Furthermore, the PLK1/FOXM1-associated tumor-cell state was linked to macrophage-related immune features and changes in the M2-like marker profile of THP-1-derived macrophage-like cells. Drug response analyses suggested differential predicted sensitivity patterns in PLK1-high tumors, providing candidate therapeutic hypotheses for further validation. CONCLUSION: The PLK1/FOXM1-associated tumor-cell state may represent a distinct molecular feature associated with proliferative activity, invasive phenotypes, and macrophage-related immune features in EC. This study provides preliminary evidence supporting the biological relevance of this molecular feature and highlights potential therapeutic directions for future investigation.

FoxM1

Comprehensive In Silico Analysis Identifies MSTO1 and LIG1 as Candidate Biomarkers With Diagnostic and Prognostic Relevance in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a major cause of cancer-related mortality worldwide. Its poor clinical outcomes are largely attributed to late-stage diagnosis and the limited accuracy of currently available diagnostic and prognostic biomarkers. Therefore, identifying novel molecular markers with improved sensitivity, specificity, and therapeutic relevance is essential for enhancing early detection and guiding personalized treatment strategies. AIMS: To identify and prioritize novel candidate HCC biomarkers with diagnostic and prognostic value and potential therapeutic vulnerability using integrated multi-omics, survival, functional dependency, and tumor microenvironment analyses. METHODS AND RESULTS: We examined the mRNA and protein expression levels of 8 DEGs in HCC tissues in the TCGA and CPTAC datasets using UALCAN, which showed that MSTO1 and LIG1 were overexpressed consistently in HCC relative to normal liver tissues. Moreover, elevated expression levels of these genes were significantly associated with higher tumor grade and advanced stage. Kaplan-Meier plotter survival data confirmed that increased expression of MSTO1 and LIG1 was associated with poorer overall survival. The DepMap CRISPR knockout data confirmed a functional dependency of both genes in HCC cell lines. CBioPortal analyses provided characterization of genomic alterations and enabled enrichment analysis of co-expressed genes, and the TCGA-UALCAN pan-cancer analyses supported the assessment of tissue specificity across tumor types. TIMER3 analyses linked candidate gene expression with immune cell infiltration patterns. Diagnostic performance by ROC analysis showed excellent discrimination for MSTO1 (AUC&#x2009;=&#x2009;0.987) and good discrimination for LIG1 (AUC&#x2009;=&#x2009;0.897). Multivariate Cox regression with Benjamini-Hochberg FDR correction across the eight genes supported MSTO1 as a candidate independent prognostic factor after adjustment for tumor stage, grade, etiology, age, and sex (HR&#x2009;=&#x2009;1.29, p&#x2009;=&#x2009;0.035), whilst LIG1 showed no independent prognostic value. Promoter methylation of MSTO1 and ADH4, assessed via UALCAN, showed that both genes were significantly differentially methylated in the promoter region of primary HCC tissues compared with normal liver tissues. Our study also confirmed the biological and clinical relevance of established HCC biomarkers: TERT, IRAK1, and ADH4. CONCLUSION: MSTO1 and LIG1 emerged as candidate diagnostic biomarkers in HCC. Additionally, MSTO1 showed a candidate prognostic association with overall survival that remained significant after adjusting for tumor stage, grade, and etiology, as well as patients' age, but not after further adjustment for AFP status. Functional data also highlighted MSTO1 as a candidate therapeutic dependency. On the other hand, LIG1 showed no independent prognostic association in either multivariate model. Their differential expression and functional essentiality in HCC cell lines highlighted their value for further experimental and independent-cohort validation before potential integration into biomarker development pipelines aimed at improving early detection and targeted therapy in HCC.

Humans

Surgical treatment of submucosal tumors of the hard palate.

Two cases have been presented to illustrated to illustrate the principles of total excisional biopsy for palatal tumors and the postoperative management of the resulting defect with the use of palatal splints. Total excisional biopsy is curative for benign tumors and for some malignant-grade tumors, and is the preferred method of treatment when possible. Total excision of the lesion with adequate margins negates the possibility of seeding the tumor into surrounding tissue or of leaving behind residual tumor.

Adenoma, Pleomorphic