Journal of the Egyptian National Cancer Institute最新文献

Background: Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis, often driven by asbestos exposure. Mutations in the NF2 gene, a key regulator of the Hippo signaling pathway, are frequently observed in PM. However, their impact on tumor biology, immune infiltration, cytokine signaling, and therapeutic response remains poorly understood.

Methods: Using data from The Cancer Genome Atlas, we analyzed 82 PM cases to assess the prevalence and consequences of NF2 mutations. Logistic regression was used to evaluate associations with clinical variables, while transcriptomic differences were examined through differential expression and functional enrichment analyses. Immune and stromal infiltration were inferred via the xCell algorithm, cytokine signaling analyzed with Cytosig, and chemotherapeutic sensitivity predicted using the pRRophetic R package. Single-cell RNA sequencing data provided further insights into transcriptional patterns in NF2-mutated tumors.

Results: NF2 mutations were present in 22% of cases, with no significant correlations to histological subtype, stage, or age. NF2-mutated tumors exhibited increased infiltration of basophils, naïve B cells, and pericytes, along with altered cytokine profiles, including NRG1, TGFB3, and reduced FGF2. Differentially expressed genes, such as MYL7 and HOXA11, were linked to poorer survival. Chemotherapy modeling indicated higher sensitivity to camptothecin and vinblastine in NF2-mutated tumors.

Conclusions: NF2 mutations influence the tumor microenvironment, transcriptional landscape, and predicted therapeutic response in PM, underscoring their potential as prognostic biomarkers. These findings support tailored therapeutic strategies targeting NF2-related pathways, including Hippo signaling and cytokine modulation.

Background: The tumor microenvironment has an important role in the growth and progression of diffuse large B-cell lymphoma (DLBCL). Immune checkpoint molecules, including PD1, LAG3, and CTLA4, are crucial to regulate the T cells function in the tumor microenvironment. Exploring the expression of these molecules in DLBCL microenvironment is crucial for developing targeted therapies enhancing anti-tumor immune responses.

Aim: This study aims to evaluate the immunohistochemical (IHC) expression of PD1, LAG3, and CTLA4 in DLBCL, assess the relation of their expression to different clinicopathological parameters and evaluate their prognostic significance.

Methods: This retrospective study encompassed 103 cases diagnosed as de novo DLBCL. Clinicopathologic and survival data were gathered. IHC for PD1, LAG3, and CTLA4 was performed.

Results: PD1, LAG3, and CTLA4 positive reaction was observed in tumor-infiltrating lymphocytes (TILs) in 68.9% (71/103), 82.5% (85/103), and 92.2% (95/103) of DLBCL cases, respectively. PD1 expression in TILs was significantly associated with hepatitis C virus (HCV) positivity and prolonged overall survival (OS) in univariate analysis. LAG3 expression in TILs was significantly associated with IPI score and tended towards shorter OS (not statistically significant). LAG3 expression in tumor cells was significantly associated with shorter disease-free survival (DFS). CTLA4 expression in TILs was significantly associated with advanced disease stage (III/IV).

Conclusion: PD1 and LAG3 are expressed mainly in TILs. PD1 expression (in TILs and tumor cells) is associated with prolonged OS, while LAG3 expression (in tumor cells) is associated with shorter DFS and its expression in TILs tended towards shorter OS. CTLA4 expression is associated with advanced disease stage but not associated with OS. These findings may suggest that immune checkpoint inhibitors targeting LAG3 may offer therapeutic potential in DLBCL by enhancing the antitumor immune response. Additional research is needed to assess the effectiveness of inhibition of these checkpoint molecules in combination with existing treatment modalities.

Objectives: Following external beam radiation therapy (EBRT) with concurrent chemotherapy, we analyzed the benefits of surgical resection for locally advanced cervical carcinoma in terms of the frequency and severity of complications and disease-free survival, including cases of adjuvant hysterectomy after failure of resolution post-brachytherapy.

Patient and methods: Retrospective analysis was utilized to determine the eligibility of 145 cases treated at the National Cancer Institute between January 2015 and June 2021. Of those, 17 patients did not match the requirements, and 8 patients declined to take part in the study. Depending on the major treatment technique, 120 FIGO stage IB3-FIGO stage IVA cervical cancer patients were split into two equal groups of 60 patients each. Sixty patients (50%) received neo-adjuvant EBRT and concurrent platinum-based chemotherapy followed by hysterectomy (group A) and 60 (50%) received definitive radiotherapy only (group B).

Results: The age at diagnosis of patients was similar, with a mean of 52.5 (range 34-77) and 53.4 (range 25 81) years in group A and group B, respectively (P = 0.675). Majority of the cases in both groups were pathologically squamous cell carcinomas (88.3% in group A and 83.3% in group B) and of grade II differentiation (73.7% in group A and 71.2% in group B). Majority of cases in both groups being FIGO stage II (45% in group A and 40% in group B) and FIGO stage III (40% in group A and 43.3% in group B). Only 17 patients (28.3%) in group A had postoperative complications, while 37 patients (61.7%) in group B suffered from post-treatment complications (P value < 0.001). In group B, 14 patients (23.3%) failed to show complete remission of the disease after completion of treatment, with a mean residual disease of 4.3 cm in diameter (range 2-6 cm), either local or nodal. Salvage hysterectomy post-definitive radiotherapy was done for 8 patients with residual disease (13.3%). In group A, 48 patients had no recurrence during follow-up (80%), while 11 of the patients had either locoregional or metastatic recurrences, or both (18.3%). DFS was comparable between both groups (P = 0.493), excluding 23.3% of group B where failure of complete remission of the disease after completion of treatment barred the patients from the disease-free calculations. The 1-year DFS was 88.1% in group A and 82.6% in group B, while the 3-year DFS was 74.1% in group A and 70.1% in group B.

Conclusion: There was no difference in disease-free survival or the incidence of locoregional and metastatic recurrence between patients with cervical cancer who had surgery and those who received brachytherapy following EBRT and concomitant chemotherapy. In almost 50% of cases, the surgical patients showed full pathological recovery.

Leukemia, a heterogeneous group of hematologic malignancies, poses significant challenges in terms of early diagnosis and effective treatment. Recent advancements in nanotechnology have paved the way for innovative approaches in leukemia management, with a particular focus on IONPs. This review paper explores the diverse designs of IONPs and their multifaceted applications in the diagnosis and treatment of leukemia. Focused discussions on the synergistic combination of IONPs with conventional chemotherapy, targeted drug delivery, and hyperthermia-based approaches provide insights into the evolving landscape of IONP-mediated leukemia therapy. The role of IONPs in overcoming drug resistance mechanisms and minimizing off-target effects is critically evaluated. The later review section provides an overview of the unique physical, chemical, and magnetic properties of IONPs, emphasizing their biocompatibility, tunable magnetic properties, and surface functionalization capabilities. The review finally addresses the challenges and prospects associated with the clinical translation of IONP-based diagnostic approaches. By addressing the challenges and opportunities in this burgeoning field, this paper aims to guide future research endeavors toward the development of effective and personalized nanotherapeutics for leukemia patients.

Purpose: This review assesses the efficacy and safety of EBRT + VBT versus VBT alone in intermediate- to high-risk endometrial cancer.

Methods: A systematic review and meta-analysis were conducted using PubMed, EMBASE, ProQuest, Ovid, and Scopus (until February 18, 2025). Studies comparing EBRT + VBT to VBT alone were included. The primary outcome was pelvic recurrence rate, while secondary outcomes included distant recurrence, overall survival, and toxicity. Data extraction, risk of bias assessment (RoB-2, ROBINS-I), and meta-analysis (random-effects models in RevMan) were performed. Certainty of evidence was evaluated using GRADE. PROSPERO registration: CRD420250654411.

Results: Eight studies comprising 2,672 patients met inclusion criteria (1,347 received EBRT + VBT; 1,325 had VBT alone). EBRT + VBT significantly reduced pelvic recurrence (OR 0.14, p = 0.001) but showed no difference in vaginal recurrence (OR 0.25, p = 0.14), distant metastasis (OR 0.78, p = 0.45) or overall survival (HR 0.82, p = 0.29, I² = 72%). EBRT + VBT was associated with higher gastrointestinal, genitourinary, and hematologic toxicity.

Conclusion: EBRT + VBT improves pelvic control but does not enhance survival and increases toxicity. VBT alone remains a viable option, highlighting the need for individualized treatment strategies.

Background: The role of the complement system and its membrane-bound regulatory proteins (mCRPs) in the pathogenesis of cancer is still a debatable issue. The current study aimed to evaluate the role of the complement regulatory protein, the decay-accelerating factor (CD55), in the pathogenesis of acute leukemia.

Methods: CD55 gene expression was assessed in the peripheral blood of 34 patients with acute myeloid leukemia (AML), 26 patients with acute lymphoblastic leukemia (ALL), and 30 healthy controls by qRT-PCR. Also, CD55 gene knockdown was performed in HSB-2 (ALL cell line) using customized short hairpin RNA (shRNA). Flowcytometric analysis was done to ensure successful transfection, and MTT assay was performed to evaluate the cell viability post-transfection and silencing of CD55.

Results: There was a significant downregulation of CD55 in acute leukemia patients compared to the healthy controls (p < 0.001) with RQ values of AML, and ALL patients were 0.2499 ± 0.07427 and 0.2581 ± 0.09467, respectively. The MTT assay showed a significantly reduced viability of HSB-2 cells following posttranscriptional silencing of CD55 (p < 0.001) by 78.6% as compared to the non-transfected or mock-transfected cells. In the presence of human serum, there was a significant reduction in cell viability by 66.3% as compared to non-transfected controls (p = 0.01). Regarding the cells co-transfected with CD55 and CD46 silencing plasmids, cell viability was significantly decreased by 70.6% compared to non-transfected cells.

Conclusion: CD55 was significantly downregulated in acute leukemia. However, its in vitro silencing showed significant reduction in cell viability, giving it a dual opposing role in cancer.

Background: Microsatellite instability (MSI) and deficiency in the human mismatch repair (MMR) system are critical drivers of genomic instability in various cancers. Tumors exhibiting MSI and MMR deficiency (dMMR) have prognostic implications and are associated with differential responses to immune checkpoint inhibitors. Given their key roles in tumorigenesis, investigating MMR protein expression and MSI in urothelial cancer of the bladder is essential to improve therapeutic strategies and deepen understanding of its molecular features. This study aimed to assess MMR protein expression and MSI in primary urothelial carcinoma of the bladder and to evaluate their associations with clinicopathological characteristics.

Methods: A total of 49 primary urothelial carcinomas were analyzed for MMR expression using immunohistochemistry, and dMMR tumors underwent further analysis for MSI status using the markers of the Bethesda panel (BAT25, BAT26, D2S123, D5S346, and D17S250). The MMR expression and MSI findings were associated with clinicopathological parameters.

Results: dMMR was identified in two high-grade urothelial carcinomas (4.1%), while the remaining cases demonstrated proficient MMR. Both dMMR tumors showed impaired immunoreactivity, with one tumor displaying a simultaneous loss of the MLH1/PMS2 heterodimer and the other showing isolated MSH6 loss. MSI analysis revealed instability in BAT26 in the MLH1/PMS2-deficient tumor and at D17S250 in the MSH6-deficient tumor. Both tumors exhibited low-level MSI (MSI-L). No relevant associations were found between MMR/MSI status and clinicopathological features (p > 0.05).

Conclusions: The identification of MSI-L and MMR deficiency in only two samples underscores the rarity of MSI in urothelial carcinoma among Tunisian patients. These findings emphasize the need for larger, multi-center studies to elucidate the MSI/dMMR molecular and clinical implications in bladder carcinoma.

Colorectal cancer (CRC) is one of the most common tumors in the world. A recent area of study for the treatment of patients with solid tumors is anti-tumor immunity. PD-1/PD-L1 inhibitors were beneficial for cancer patients with multiple tumor types. However, their efficacy for CRC is low. Thus, there is an urgent need to explore additional co-inhibitory tools such as VISTA for CRC treatment.ObjectiveThe current study aimed to evaluate expression of VISTA on T cell subsets in patients with CRC and its correlation with other prognostic markers.Patients and methodsThe study included 31 patients with CRC and 25 healthy controls. All participants were subjected to full history taking, clinical examination, routine laboratory investigations, and flow cytometric detection of VISTA expression on T cell subsets on peripheral blood (PB). In addition to detection of VISTA expression on T cell subsets on tissue samples of both malignant CRC and normal colon tissue of the CRC patients.ResultsIn the peripheral blood, the expression of VISTA on CD4⁺ T helper and CD8⁺ T cytotoxic cells was significantly higher in CRC patients than the normal controls. There was no significant difference in VISTA expression on double positive T cells (CD4⁺CD8⁺) between the CRC patients and normal controls. In tissue samples, expression of VISTA on CD4 + T helper, CD8 + T cytotoxic, and double positive T (CD4 + CD8 +) cells in the malignant tissue of CRC patients was significantly higher than that in normal colonic tissue. Also, in CRC patients, the expression of VISTA on CD4⁺ T helper, CD8⁺ T cytotoxic, and double positive T cells in both malignant CRC tissue and normal colonic tissue was significantly higher than its expression PB.ConclusionThe higher expression of VISTA in CRC patients than the healthy controls and its higher levels in malignant CRC tissue and normal colonic tissue than PB of CRC patients suggest the role VISTA in the pathogenesis of CRC.

Background: The effectiveness of radioiodine therapy (RAI) in reducing recurrence and improving overall survival in differentiated thyroid carcinoma (DTC) remains debated. This systematic review evaluates the impact of RAI on DTC recurrence and survival.

Methods: A comprehensive search was conducted across PubMed, ScienceDirect, Web of Science, CINAHL, and Tripdatabase, including studies from inception to August 2024. Only studies published in English with full-text availability were included. Risk of bias was assessed using the Revised Risk of Bias Assessment Tool for Nonrandomized Studies of Interventions (RoBANS 2).

Results: Nine studies were included, involving 161,703 participants (36,658 men and 125,045 women). The studies were geographically diverse, with four from the American continent, three from Asia, and two from Europe. RAI doses ranged from 30 to 300 mCi, with 30 mCi and 100 mCi being the most common. Five studies found that RAI reduced recurrence, while two found no significant effect. The median time to recurrence ranged from 10 months to 15 years, with most studies indicating a 1-2-year median. Regarding overall survival, two studies reported improvement with successful RAI therapy, while two found no significant impact.

Conclusion: RAI therapy shows potential in reducing recurrence in DTC, particularly within the first 2-year post-treatment, but its effect on overall survival remains unclear. Further high-quality research is necessary to confirm these findings and guide clinical practice.

Background: Fibromas are common ovarian stromal tumors, while steroid cell tumors (SCTs) are rare, accounting for < 0.1% of ovarian neoplasms. Approximately, one-third of SCTs exhibit malignant behavior, but predicting malignancy remains challenging.

Case presentation: A 73-year-old woman presented with nonspecific pelvic pain, and imaging revealed multiple pelvic masses. She underwent a simple hysterectomy and bilateral adnexectomy. Pathological examination revealed a unique colocalization of a fibroma and a SCT in the right ovary. One year later, the SCT recurred with lymph node metastasis. Morphological analysis and whole exome sequencing suggested a shared origin for the fibroma and SCT components. Notably, two missense mutations in MUC4 were identified in the SCT, with immunohistochemistry confirming MUC4 overexpression. Steroidogenesis patterns in the SCT resembled those of adrenocortical carcinoma, indicating disorganized steroidogenesis and potentially explaining the absence of clinical endocrine abnormalities.

Conclusion: This case underscores the rarity and complexity of concomitant ovarian fibroma and malignant SCT. The identification of MUC4 mutations and disorganized steroidogenesis may provide insights into the pathogenesis of malignant SCTs. Further research is needed to understand the mechanisms and clinical implications of malignant SCT.