Prognostic Implications of CD24, SOX2, and Nanog Expression in Invasive Urothelial Carcinoma.

BACKGROUND: Urinary bladder cancer (BC) is the seventh most common cancer worldwide with the highest incidence rates in Western Europe, North America, and Australia. The most common type of BC is urothelial carcinoma (UC), which represents a significant cause of morbidity and mortality. OBJECTIVE: The aim of the study was to evaluate the prognostic value of CD24, SOX2, and Nanog in UC cases and the correlation with recurrence and survival. MATERIALS AND METHODS: In this study, the authors investigated the expression of CD24, SOX2, and Nanog in 80 patients with urinary BC. The clinical significance of the markers was evaluated by assessing the correlation with the clinicopathologic parameters and prognosis. RESULTS: The CD24 expression was positive in 62.5% of the BC patients, there was a significant association between CD24 expression and high grade and stage and lymphovascular invasion (LVI), P (0.002, 0.0010, and 0.001). SOX2 was expressed in 60 patients (75%), the expression was significantly associated with age, stage, grade, LVI, lymph node, and smoking, P (0.016, 0.01, <0.001, 0.003, 0.036, and 0.002), respectively. Nanog expression was positive in 60% of the BC patients. There was a significant association between Nanog expression and age, high grade, high stage, and LVI ( P =0.016, <0.001, and 0.003), respectively. CONCLUSIONS: A significant relation between CD24, SOX2, and Nanog with the invasive potential of UC. This increase in expression of the 3 markers with the grades and stages of UC suggests that they can play a role in the development of UC, so they can be used in targeted therapy in the future.

The Value of Immunohistochemical Expression of TOX, ICOS, and GATA-3 in the Diagnosis of Mycosis Fungoides.

BACKGROUND: Mycosis fungoides (MF) is considered the commonest type of cutaneous T-cell lymphoma representing about 50% of all primary cutaneous lymphomas. Differentiation between MF and another inflammatory dermatitis (BIDs) is important to ensure proper management. AIM: We aimed to evaluate the immunohistochemical expression of T OX, ICOS, and GATA binding protein 3 (GATA-3) in early stages MF (stage IA and IB) to establish their diagnostic value and to guide the use of inhibitors in the treatment of cutaneous T-cell lymphomas. MATERIALS AND METHODS: A retrospective study of 75 skin paraffin blocks (punch biopsy) 40 cases of MF and 35 cases of eczematous dermatitis as a group representing other inflammatory dermatitis were retrieved from archives of the pathology department of our University, during the period from October 2017 to May 2021. RESULTS: About 98% and 90% of patients in the MF group had positive T OX and ICOS, while 70% of them had positive GATA-3. High expression of T OX, ICOS, and GATA-3 was associated with higher stages. CONCLUSIONS: T OX is considered a diagnostic marker for early MF. The importance of identifying novel markers in MF expressed by immunohistochemistry, such as ICOS, has been established. According to our results, GATA-3 could be used as an accessory marker in the diagnosis of MF when combined with T OX and ICOS in a panel.

Expression of HnRNP A1, ZEB1, and E-cadherin in Hepatocellular carcinoma and their impact on patients' prognosis and survival.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in Egypt. HCCs usually have a poor prognosis because of late diagnosis, aggressive metastasis, and early invasion. Heterogeneous ribonucleoproteins (HnRNPs) are nuclear proteins that play a variety of roles in telomere formation, DNA repair, cell signaling, and gene regulation. .: Zincfinger Eboxbinding homeoboxes (ZEBs) are transcription factors that have a consistent inverse correlation with Ecadherin in numerous types of cancer and associated with poor prognosis. Aim: This study aimed to verify the prognostic expression of HnRNP A1, ZEB1, and E-cadherin in HCC. Settings and Design: The retrospective study consisted of 54 formalin-fixed paraffin-embedded tissue blocks of hepatocellular carcinoma. Methods and Material: Immunohistochemical staining was performed using antibodies against HnRNP A1, ZEB1, and E-cadherin. The patients were followed at the Clinical Oncology Department from May 2018 to July 2021. Statistical Analysis: SPSS version 20 using the Chi-square test to compare data and the Kaplan-Meier plot for comparing survival. Results: HnRNP A1 high positivity was detected in 59.3% of the cases, whereas negative E-cadherin and ZEB 1 expression presented in 37% and 70.4% of the patients, respectively. A statistically significant relation was present between HnRNP A1, ZEB1, E-cadherin, and various clinicopathological variables. The mean progression-free survival and overall survival in low HnRNP A1 and negative ZEB1 expressions were longer than those exhibited in high HnRNP A1 and positive ZEB1 expressions. Conclusion: HnRNP A1 and ZEB1 expressions are poor prognostic factors of HCC. E-cadherin has an important role in the development of differentiated HCCs and favorable outcome.

Clinicopathological implications of genetic and immunohistochemical expression of S100A8, S100A9 and TLR5 in breast carcinoma / Implicaciones clinicopatológicas de la expresión genética e inmunohistoquímica de las expresiones S100A8, S100A9 y TLR5 en el carcinoma de mama

Introduction: Breast carcinoma (BC) is one of the most common cancer-related mortality among women worldwide. S100A9 and S100A8 are calcium-binding proteins involved in BC metastasis. Toll-like receptors (TLRs) are membrane-bound proteins that play a vital role in immune systems and carcinogenesis through inflammatory cytokines.Objectives: We aimed to evaluate of S100A8, S100A9 and TLR5 in breast carcinoma by IHC, their gene expression by PCR and investigate their correlation with clinicopathological characters and hormone status.Materials and methods: This study was done in Biochemistry & Molecular Biology and Pathology Departments, Zagazig University, Egypt. Biopsy was taken from 72 patients with invasive breast carcinoma cases admitted to Surgery Department, Zagazig University, between January 2018 and January 2021. 72 breast biopsies were obtained from adjacent normal breast (as a control). IHC, gene expression by q real-time PCR using S100A8, S100A9 and TRL5.Results: Positive S100A8, S100A9, TLR5 were 81.9%, 76.4%, 86.1% respectively with statistically significant association between advanced stage, presence of lymph node metastasis, ER.PR status and HER2 negative expression.Conclusiones: Based on our findings, we postulated that S100A8, S100A9, TLR5 play an important role in progression of BC and can be used as novel molecular targets for earlier BC detection and prediction for future therapies in breast carcinoma. (AU)

Introducción: El carcinoma de mama (BC, por sus siglas en inglés) es una de las muertes relacionadas con el cáncer más comunes entre las mujeres en todo el mundo. S100A9 y S100A8 son proteínas de unión al calcio implicadas en la metástasis del BC. Los receptores tipo peaje (TLR, por sus siglas en inglés) son proteínas unidas por membrana que juegan un papel vital en los sistemas inmunitarios y carcinogénesis a través de citocinas inflamatorias.Objetivos: Evaluar S100A8, S100A9 y TLR5 en el BC por IHC, su expresión génica por PCR e investigar su correlación con los caracteres clínico patológicos y el estado hormonal.Material y métodos: Este estudio se realizó en los Departamentos de Bioquímica y Biología Molecular y Patología de la Universidad de Zagazig, Egipto. Se tomó biopsia de 72 pacientes con carcinoma de mama invasivo ingresados en el Departamento de Cirugía de la Universidad de Zagazig, entre enero de 2018 y enero de 2021. Setenta y dos biopsias de mama se obtuvieron de mama normal adyacente (como control). IHC, expresión génica por q PCR en tiempo real usando S100A8, S100A9 y TRL5.Resultados: Positivo S100A8, S100A9 y TLR5 fueron del 81,9, 76,4 y 86,1%, respectivamente, con asociación estadísticamente significativa entre el estadio avanzado, la presencia de metástasis en los ganglios linfáticos, el estado de ER.PR−, expresión negativa de HER2.Conclusiones:Sobre la base de nuestros hallazgos, postulamos que S100A8, S100A9 y TLR5 juegan un papel importante en la progresión del BC y pueden utilizarse como nuevas dianas moleculares para la detección temprana del BC y la predicción para futuras terapias en el BC. (AU)

Immunohistochemical expression of Neurogenic Locus Notch Homolog 4 (Notch4) in invasive breast carcinoma: Correlation with clinicopathological parameters and immunohistochemical-based subtypes / Expresión inmunohistoquímica del homólogo 4 del Notch del locus neurogénico (Notch4) en el cáncer de mama invasivo: correlación con los parámetros clínico-patológicos y los subtipos con base inmunohistoquímica

Introduction Starting out with its discovery as small notches on fly wings, Neurogenic Locus Notch Homolog 4 (Notch4) signaling has been sparked as unique pathway implicated in cellular multiplication, differentiation, and regulation of stem cells. Its aberrant activation causes arrays of cancers including breast cancer. Objectives The aim of the present study was to evaluate the immunohistochemical expression level of Notch4 and its subcellular localization in invasive breast carcinoma. The correlation between Notch4 expression and both of clinicopathological parameters and immunohistochemical-based subtypes of studied cases was also assessed. Methods and materials Immunohistochemical expression of Notch4 receptor was examined in 60 specimens of paraffin-embedded sections of invasive breast cancer. Normal and hyperplastic breast tissue adjacent to carcinoma cells was also included in the study. Results There was a significant increase in the expression level of Notch4 protein in breast cancer, compared to that of normal breast tissue and hyperplastic breast lesions. Also, there was a statistical significant correlation between Notch4 expression level and tumor size, tumor grade, nodal metastasis, lymphovascular invasion, human epidermal growth factor receptor 2 (her2) status, Her2-enriched and triple negative subtypes, and Ki67. Furthermore, an inverse significant correlation was found between Notch4 expression and both of age and estrogen receptor (ER). No statistical significant correlation was found between Notch4 expression and tumor histological subtypes, Tumor infiltrating lymphocytes (TILs), and fibrosis. Conclusion Notch4 overexpression has been implicated in breast cancer development, progression and emergence of aggressive biological phenotypes. (AU)

Introducción Empezando por su descubrimiento como pequeños surcos en las alas de la mosca, la vía de señalización del homólogo 4 del Notch del locus neurogénico (Notch4) se ha revelado como la única vía implicada en la multiplicación y diferenciación celular, y regulación de las células madre. Su activación aberrante causa una serie de cánceres, incluyendo el cáncer de mama. Objetivos El objetivo del presente estudio fue evaluar el nivel de expresión inmunohistoquímica de Notch4, así como su localización subcelular en el cáncer de mama invasivo. También se evaluaron la correlación entre la expresión de Notch4 y los parámetros clínico-patológicos y subtipos con base inmunohistoquímica de los casos estudiados. Métodos y materiales Se examinó la expresión inmunohistoquímica del receptor de Notch4 en 60 muestras de secciones parafinadas de cáncer de mama. También se incluyeron en el estudio células hiperplásicas de tejido de mama, adyacentes al carcinoma. Resultados Se produjo un incremento significativo del nivel de expresión de la proteína Notch4 en el cáncer de mama, en comparación con el tejido normal de la mama y las lesiones de mama hiperplásicas. De igual modo, se produjo una correlación estadísticamente significativa entre el nivel de expresión de Notch4 y el tamaño y el grado tumoral, el desarrollo de nódulos metastásicos, la invasión linfovascular, el estatus de Her2 (receptor 2 del factor de crecimiento epidérmico humano), los subtipos Her2 enriquecido y triple negativo, y Ki-67. Además, se encontró una correlación significativa inversa entre la expresión de Notch4 y la edad, y el receptor de estrógenos (ER). No se encontró correlación estadísticamente significativa entre la expresión de Notch4 y los subtipos histológicos del tumor, linfocitos infiltrantes tumorales (TIL) y fibrosis. Conclusión... (AU)