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Two prostate carcinoma cell lines, DU-145 and PC-3, were examined for abnormalities in the retinoblastoma (Rb) and the p53 putative tumor suppressor genes. We found an abnormal Rb gene product in DU-145 using Western blot analysis. Polymerase chain reaction amplification followed by direct DNA sequencing demonstrated a base substitution mutation that generates a stop codon in exon 21. On Northern, Southern, and Western blot analysis, the p53 gene and its product appear to be normal in DU-145. PC-3, however, failed to demonstrate expression of either the p53 transcript on Northern blot analysis or the p53 protein on Western blot analysis, while the Rb gene products appeared to be normal on both Northern and Western blot analysis. This work extends the correlation between abnormal expression of putative tumor suppressor genes and human malignancies.

Patients with bone metastases may experience debilitating pain, neurological conditions, increased risk of pathological fractures, and death. A deeper understanding of the bone microenvironment, the molecular biology of cancer types prone to metastasis, and how bone physiology promotes cancer growth, may help to uncover targeted treatment options. The purpose of this paper is to outline the current concepts relevant to topics including bone remodeling, angiogenesis, and immunomodulation as it relates to metastatic bone disease.

Background and Objectives: Adoption of molecular classification in endometrial cancer (EC) into clinical practice remains challenging due to complexity in coordination of multiple assays. We aimed to develop a simple molecular technique to classify ECs into four subgroups using our custom-designed targeted sequencing panel., Methods: Patients with newly diagnosed ECs were prospectively recruited from three cancer centres in Ontario, Canada. Using our panel, 181 ECs were sequenced. Variants were analysed for pathogenicity and clinicopathologic information was collected through medical records retrospectively., Results: Of 181, 86 (48%) were mismatch repair deficient (MMRd), of which 62 (72%) harboured MLH1 promoter methylation and 24 (28%) had pathogenic variants in MMR genes. Of single classifiers, three (1.8%) had pathogenic POLE (POLEmut), 15 (9%) had TP53 mutations (p53abn) and 61 (37%) had no specific molecular profile subtype (NSMP). Sixteen (9%) had more than one molecular classifying feature, with eight (4%) MMRd-p53abn, six (3%) POLEmut-MMRd, one (0.5%) POLEmut-MMRd-p53abn and one (0.5%) POLEmut-p53abn. When MMRd group was further subclassified according to mechanism of MMR loss, MLH1 promoter methylated group had worse outcomes than those with somatic MMR pathogenic variants., Conclusions: Our panel can classify ECs into four subgroups through a simplified process and can be implemented reflexively in clinical practice., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Musculoskeletal oncology involves rare diseases. As a result, there is a paucity of literature to guide practitioners. Studies are often clinical experience, retrospective reviews, noncomparative studies, and involve small numbers of patients. However, technological advances consistently arise in this field. This article represents the Musculoskeletal Tumor Society efforts to improve multispecialty collaboration and research credibility. It involves brief systematic reviews of novel ideas and suggests high-quality research needed to provide and standardize best practices within this field., (© 2024 Wiley Periodicals LLC.)

Racial disparities in surgical oncology research funding significantly impact minority researchers and diverse populations. This review explores historical factors contributing to the underrepresentation of minorities in academic medicine. Strategies for addressing these disparities include enhancing diversity in the physician workforce and improving funding opportunities for minority researchers, with the goal of improving patient outcomes and reducing cancer care disparities., (© 2024 Wiley Periodicals LLC.)

Background: Despite the well-known prognostic role of lymph node metastasis (LNM) in pNETs, less is known about the importance of lymphovascular invasion (LVI) among patients with these tumors., Methods: Patients undergoing pancreatectomy for pNET between 2002 and 2020 were identified in the US Neuroendocrine Tumor Study Group database. Cox regression analysis was utilized to identify the impact of LVI on recurrence-free survival (RFS) among patients with node-negative pNET., Results: Among 853 patients who underwent resection for pNET, 214 patients (25.1%) had LNM, while 116 (13.6%) and 523 individuals (61.3%) were LVI + N0 and LVI - N0, respectively. The overall incidence of LVI among patients with N0 pNET was 18.1%; the incidence of LVI increased with increasing tumor size and Ki-67 levels (size < 2 cm and Ki-67 < 3%: 5.5%; size < 2 cm and Ki-67 ≥ 3%: 17.2%; size ≥ 2 cm and Ki-67 < 3%: 22.2%; size ≥ 2 cm and Ki-67 ≥ 3%: 43.1%, p < 0.001). Five-year RFS was highest among patients with LVI - N0 disease followed by individuals with LVI + N0 and N+ pNETs (92.8% vs. 61.6% vs. 58.3%, p < 0.001). On multivariable analysis, the presence of LVI on pathology remained independently associated with almost 2.5 times higher hazards of recurrence (HR 2.47, 05% CI 1.44-4.24) among individuals with N0 pNETs., Conclusion: The incidence of LVI varied according to tumor size and Ki-67. LVI was associated with a higher likelihood of recurrence among individuals who underwent formal pancreatic resection for N0 pNETs. LVI is an important prognostic indicator among patients with node-negative pNETs., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Cytoreductive surgery with HIPEC has definite application to the management of selected patients with peritoneal metastases. Patients who profit most have a complete cytoreductive surgery. Higher-grade tumors such as colorectal cancer, gastric cancer, and ovarian malignancy are benefited by CRS and HIPEC only under limited circumstances. High-grade tumor invades subperitoneal lymphatics where HIPEC is not effective. Options to traditional HIPEC for treatment of invasive intraabdominal malignancies with peritoneal metastases must be explored., (© 2024 Wiley Periodicals LLC.)

Background and Objectives: Hepatic epithelioid hemangioendothelioma (HEHE) is an uncommon vascular neoplasm characterized by variable clinical behavior. Our aim was to describe the therapeutic approach for HEHE at diagnosis and define clinicopathological characteristics associated with tumor progression and long-term survival., Methods: This is a retrospective study that includes patients with HEHE who received treatment at Mayo Clinic Rochester between 1984 and 2023., Results: Eighty patients were included in the study (median age: 44 years; 62.5% female), 24 underwent liver transplantation, 26 underwent liver resection, and 30 were managed medically. The 3-year overall survival rates were 86.7%, 80.9%, and 51.1%, respectively. Notably, 26 patients had extrahepatic metastases at the time of diagnosis, four (16.7%) in the transplantation group, four (15.4%) in the resection group, and 18 (69.2%) in the nonsurgical group. On multivariable modeling, bone metastasis was independently associated with long-term mortality (HR 6.3, p < 0.001) while lung metastasis and surgical intervention were not associated with long-term mortality (HR 0.8, p = 0.8; HR 1.1, p = 0.9, respectively)., Conclusion: Bone metastasis emerged as a strong predictor of poor survival. Hence, aggressive surgical intervention may not be advantageous in patients with skeletal metastases but can still be offered for those with other extrahepatic metastases., (© 2024 Wiley Periodicals LLC.)

Background and Objectives: Not all gastric neuroendocrine tumors (GNETs) may be classified into one of the three described clinicopathologic subtypes. The purpose of this study was to better characterize GNET subtypes and associated outcomes., Methods: Patients treated for GNET at our institution (1995-2021) were identified. Pathologic specimens of tumors that could not be classified as type 1, 2, or 3 were further reviewed. GNETs were categorized as proton pump inhibitor (PPI)-associated based on changes in the background gastric mucosa consistent with PPI use. Distant metastasis at presentation (DM) and disease-specific survival (DSS) were evaluated., Results: Among 246 patients, there were 164 (67%) type 1, 5 (2%) type 2, 52 (21%) type 3, and 18 (7%) PPI-associated GNETs. Seven (3%) tumors remained unclassified. DM was more frequent with type 3 GNETs (38%) than type 1 (1%), type 2 (20%), or PPI-associated tumors (11%, p < 0.001). Ten-year DSS rates were 100% for type 1, 53% (95% confidence interval [CI], 38%-75%) for type 3, and 80% (95% CI, 58%-100%) for PPI-associated tumors (p < 0.001). GNET subtype, race, and DM were independently associated with DSS., Conclusions: PPI-associated tumors may represent a distinct GNET subtype with intermediate outcomes. Other factors should also be considered in overall prognosis., (© 2024 Wiley Periodicals LLC.)

Background: The integration of artificial intelligence (AI), particularly, in oncology, has significantly shifted the paradigms of medical diagnostics and treatment planning. However, the utility of AI, specifically OpenAI's ChatGPT, in soft tissue sarcoma treatment, remains unclear., Methods: We evaluated ChatGPT's alignment with the Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of soft tissue tumors 2020. Twenty-two clinical questions (CQs) were formulated to encompass various aspects of sarcoma diagnosis, treatment, and management. ChatGPT's responses were classified into "Complete Alignment," "Partial Alignment," or "Nonalignment" based on the recommendation and strength of evidence., Results: ChatGPT demonstrated an 86% alignment rate with the JOA guidelines. The AI provided two instances of complete alignment and 17 instances of partial alignment, indicating a strong capability to match guideline criteria for most questions. However, three discrepancies were identified in areas concerning the treatment of atypical lipomatous tumors, perioperative chemotherapy for synovial sarcoma, and treatment strategies for elderly patients with malignant soft tissue tumors. Reassessment with guideline input led to some adjustments, revealing both the potential and limitations of AI in complex sarcoma care., Conclusion: Our study demonstrates that AI, specifically ChatGPT, can align with clinical guidelines for soft tissue sarcoma treatment. It also underscores the need for continuous refinement and cautious integration of AI in medical decision-making, particularly in the context of treatment for soft tissue sarcoma., (© 2024 Wiley Periodicals LLC.)