The Role of Epithelial Cell Adhesion Molecule Cancer Stem Cell Marker in Evaluation of Hepatocellular Carcinoma.

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher's exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann-Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM's role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.

Primary Tuberculosis of Tonsils: Interesting Case Detected During the Histopathological Examination.

Despite being a preventable and curable disease, tuberculosis, which mainly affects the lungs, is still a major cause of illness and death worldwide, with more than one million people dying from it each year. The affliction of the tonsils is uncommon, and isolated tonsillar tuberculosis in the absence of active pulmonary disease is an extremely rare condition that requires early and accurate diagnosis to provide proper management. Microscopic examination is one of the gold-standard tools for diagnosing tuberculosis. However, routine histopathological investigation for tonsillectomy specimens is not justified except in cases of unusual clinical or postoperative presentations. A 20-year-old female patient who experienced recurrent episodes of infections with enlarged tonsils and adenoids and showed a slightly unusual presentation was sent for a histopathology examination. Upon microscopic examination, a caseating granulomatous reaction was found, and staining for acid-fast bacilli tested positive. The patient was treated for tuberculosis of the tonsils, and their condition improved.

Expression of p16 protein in breast cancer.

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

High-Grade Spindle Cell Sarcoma of the Scalp With an MGA::NUTM1 Gene Fusion in a Pediatric Patient.

ABSTRACT: NUT carcinoma (NC) is a rare and aggressive neoplasm associated with a poor prognosis. NC is characterized by a NUTM1- rearrangement on chromosome 15q14, commonly fused with the BRD4 or BRD3 gene . A rare subset of NC defined by fusion of NUTM1 with the MGA gene has been identified, showing mesenchymal differentiation on histology. Few cases of spindle cell sarcomas harboring MGA::NUTM1 gene fusions have been reported in the literature. We describe a case of spindle cell sarcoma harboring an MGA::NUTM1 fusion in a 6-year-old male patient. In contrast to typical cases of spindle cell carcinomas or NC, NUTM1 fusion-positive sarcomas are associated with a better prognosis. This report highlights the importance of diagnostic workup of undifferentiated neoplasms, as identification of the MGA::NUTM1 fusion in spindle cell sarcoma could be used in treatment algorithms and lead to better outcomes, to the benefit of patients.

Prognostic value of glucose transporter proteins-1 (GLUT1) in breast carcinoma.

Several studies have reported increased glucose transporters (GLUT) expression in different cancer types, including breast cancer. The primary purpose of this study is to examine GLUT1 immunoexpression in breast cancer patients in Saudi Arabia and to determine its significance. The study examined the association between GLUT1 immunophenotype and the clinicopathological characteristics in breast cancer. GLUT1 expression was analyzed in retrospectively collected tissue samples (n = 578) from breast cancer patients using immunohistochemistry. A total of 311 (54%) of the cases expressed GLUT1 cytoplasmic immunohistochemical staining. In univariate analysis, we found a significant association between GLUT1 expression and high-grade tumors (p < 0.0001). Positive estrogen and progesterone receptor results predicted lower GLUT1 immunoexpression (p < 0.0001 for both). Vascular invasion showed a significant association with GLUT1 immunoexpression (p = 0.045). Our findings support that GLUT1 immunohistochemistry can be used as a marker to determine the grade and hormonal receptor status in breast cancer.

The Expression of Stem Cell Marker LGR5 and Its Coexpression with Β-Catenin in Sporadic Colorectal Carcinoma and Adenoma: A Comparative Immunohistochemical Study.

Background: LGR5 is one of the most important stem cell markers for colorectal cancer (CRC), as it potentiates Wnt/Β-catenin signaling. The well-characterized deregulation of Wnt/Β-catenin signaling that occurs during adenoma/carcinoma sequence in CRC renders LGR5 a hopeful therapeutic target. We assessed the immunohistochemical expression of LGR5 and Β-catenin in normal colonic and tumorous lesions with a clinicopathological correlation. Methods: Tissue blocks and clinical data of 50 selected cases were included: 8 from normal mucosa, 12 cases of adenoma, and 30 cases of CRC, where sections were cut and re-examined and the immunohistochemical technique was conducted using anti-LGR5 and anti-Β-catenin to measure the staining density. Results: There was no expression of LGR5 in normal mucosa compared to samples of adenoma and CRC samples. The association analysis showed that CRC specimens were more likely to have strong LGR5 and Β-catenin expressions than the other two groups (p = 0.048 and p < 0.001, respectively). Specimens with high-grade dysplastic adenoma were more likely to express moderate-to-strong expression of LGR5 and Β-catenin (p = 0.013 and p = 0.036, respectively). In contrast, there were no statistically significant associations between LGR5 and Β-catenin expression with grade and stage. Conclusion: These results suggest and support the possible role of LGR5 as a potential marker of cancer stem cells in sporadic colorectal carcinogenesis in addition to a prognostic value for LGR5 and Β-catenin in adenomatous lesions according to immunohistochemical expression density. A potential therapeutic role of LGR5 in CRC is suggested for future studies based on its role in pathogenesis.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

INTRODUCTION: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. METHODS: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. RESULTS AND CONCLUSION: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Identification of Novel Mutations in Colorectal Cancer Patients Using AmpliSeq Comprehensive Cancer Panel.

Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. Discovery of novel variants in local population provides confident targets for developing biomarkers for personalized medicine. We identified the need to generate high-quality sequencing data from local colorectal cancer patients and understand the pattern of occurrence of variants. In this report, we used archived samples from Saudi Arabia and used the AmpliSeq comprehensive cancer panel to identify novel somatic variants. We report a comprehensive analysis of next-generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity, and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in the large intestine. APC, RET, and EGFR genes were most frequently mutated. A higher number of variants were identified in the left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.

Adenoid cystic carcinoma of the upper airway mimicking a thyroid tumor: A case report.

Adenoid cystic carcinoma (ACC) is a rare malignant tumor, reportedly representing <1% of all head and neck cancers. There have been few reported cases of ACC of the upper airway presenting as a midline mass. This is the case report of a 47-year-old female patient who presented with such a midline neck mass. The mass was approached and investigated as a thyroid mass, but was ultimately found to be a tracheal tumor with thyroid invasion. We herein discuss in detail the patient history, investigation and treatment.