PARP1, BRCA1 and androgen receptor expression in triple-negative breast cancer patients treated with neoadjuvant chemotherapy / Expresión de receptores de PARP1, BRCA1 y andrógenos en pacientes de cáncer de mama triple negativo tratados con quimioterapia neoadyuvante

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype, where no effective therapies have been established for it. Searching for therapeutic targets for TNBC patients is the aim of the current research. Poly adenosine diphosphate ribose polymerase (PARP1) inhibitors are promising antitumor therapy that have a high potency in BRCA1-deficient breast cancers. Materials and methods: Forty TNBC patients who received neoadjuvant chemotherapy (NAC) were enrolled in this study, and evaluated for PARP1, BRCA1, and Androgen receptor (AR) immunohistochemical expression before and after receiving NAC. Data of patients' clinical and pathological responses to the chemotherapy were collected and finally analyzed. Results: The immunohistochemical results revealed 10 cases (25%) positive for AR, while 18 cases (45%) and 22 cases (55%) expressed PARP1 at low and high levels, respectively. Twelve cases (30%) and 28 cases (70%) expressed BRCA1 at low and high levels, respectively. There was a significant difference between PARP1 expression in normal and malignant tissues (P < 0.001). Higher PARP1 expression was correlated with a better overall clinical response (OAR) and pathological complete response (pCR) (P = 0.018, 0.01 respectively). Co-expression of both PARP1 & BRCA1 was correlated with OAR and pCR. Chemotherapy decreases PARP1 protein levels in matched patient samples (P = 0.015). Positive AR expression was correlated with BRCA1 overexpression. Conclusion: PARP1 is highly expressed in TNBC with a better OAR and pCR especially in cases with high BRCA1, so it might be considered as a therapeutic target for this risky group. (AU)

Introducción: El cáncer de mama triple negativo (TNBC) es un subtipo agresivo, donde no se han establecido terapias efectivas para este cáncer. La búsqueda de dianas terapéuticas para pacientes con TNBC es el objetivo de la investigación actual. Los inhibidores de la poli adenosina difosfato ribosa polimerasa (PARP1) son prometedores terapia antitumoral que tienen una alta potencia en los cánceres de mama deficientes de BRCA1. Materiales y métodos: Cuarenta pacientes de TNBC que recibieron quimioterapia neoadyuvante (NAC) se inscribieron en este estudio y se evaluaron para la expresión inmunohistoquímica de PARP1, BRCA1 y receptores de andrógenos (AR) antes y después de recibir NAC. Se recogieron y finalmente se analizaron los datos de las respuestas clínicas y patológicas de los pacientes a la quimioterapia. Resultados: Los resultados inmunohistoquímicos revelaron 10 casos (25%) positivos para AR, mientras que 18 casos (45%) y 22 casos (55%) expresaron PARP1 en niveles bajos y altos, respectivamente. Doce casos (30%) y 28 casos (70%) expresaron BRCA1 en niveles bajos y altos, respectivamente. Hubo una diferencia significativa entre la expresión de PARP1 en tejidos normales y malignos (P 0.001). Una mayor expresión de PARP1 se correlacionó con una mejor respuesta clínica global (OAR) y una respuesta patológica completa (pCR) (P = 0,018, 0,01 respectivamente). La co-expresión de ambos PARP1 y BRCA1 se correlacionó con OAR y pCR. La quimioterapia disminuye los niveles de proteína PARP1 en muestras de pacientes emparejadas (P = 0,015). La expresión positivos de AR se correlacionó con la expresión de BRCA1. Conclusión: El PARP1 está muy expresado en TNBC con una mejor OAR y pCR especialmente en casos con BRCA1 alto, por lo que podría ser considerado como una diana terapéutica para este grupo de riesgo. (AU)

RON, ROR1 and SUSD2 expression in tissues of endometrial carcinoma patients. Clinicopathological and prognostic implications.

Introduction: Endometrial carcinoma is now considered a common female gynecologic cancer with increasing incidence, with 13-25% of patients being still liable to recurrence and metastasis, which needs further studies to detect novel targets and new therapies. The aim of the study was evaluate tissue expression of RON, ROR1 and SUSD2 in endometrial carcinoma and atypical endometrial hyperplasia using immunohistochemistry and correlate their expression with clinical, pathological and prognostic parameters of patients. Material and methods: We included samples from 100 patients with endometrial carcinoma. Sections from paraffin blocks were stained with RON, ROR1 and SUSD2 using immunohistochemistry. Correlations between marker expression, clinicopathological features and prognostic samples were evaluated. Results: Upregulation of RON and ROR1 and downregulation of SUSD2 expression were found in endometrial carcinoma more than atypical endometrial hyperplasia (p < 0.001). High RON and ROR1 expression levels were significantly associated with high grade (p < 0.001), presence of lymph node metastases (p = 0.003), distant metastases (p = 0.009), advanced International Federation of Gynecology and Obstetrics stage (p = 0.002), poor response to therapy (p = 0.046), and lower recurrence-free survival (RFS) rate (p = 0.002), progression-free survival (PFS) rate (p = 0.008), distant metastasis-free survival (DMFS) rate (p = 0.019) and overall survival rate (p < 0.001). Low SUSD2 expression was significantly associated with older patient age (p = 0.002), large tumor size (p = 0.003), high grade (p = 0.005), presence of adnexal invasion (p = 0.023), presence of lympho-vascular invasion (p = 0.021), extent of myometrial invasion (p = 0.002), lower RFS rate (p = 0.008), lower PFS rate (p = 0.023), and lower DMFS rate (p < 0.001). Conclusions: Upregulation of RON and ROR1 and downregulation of SUSD2 lead to promotion of endometrial cancer cell proliferation, migration, epithelial-mesenchymal transition, and invasion.

A comparison between different management surgical approaches in the treatment of splenic flexure colon cancer

Background: There are many surgical approaches which described extent of resection of the colon for adequate surgicalmanagement of splenic flexure cancer, but up till now there is no established surgical procedure, this is because the presence of double lymphatic drainage of themesenteric vessels. Segmental resection of the colon for the management of splenic flexure cancer was a recently accepted surgical procedure. Objective: In the present study, we aimed to compare three surgical management techniques to clarify the best management approach of Egyptian patients with splenic flexure cancer regarding operative, clinical, and oncological outcomes: segmental resection, and extended left or right hemicolectomy,. Materials and Methods In the present study, we included 90 patients with splenic flexure cancer. Cases were divided into 3 groups. Each group included 30 patients in order to compare three surgical techniques: segmental resection, extended left hemicolectomy, and extended right hemicolectomy. Results: We have found no statistically significant differences between the three included groups regarding operative findings, postoperative complications, local recurrence, distant recurrence, disease progression, recurrence-free survival rate, progression-free survival rate, and overall survival rate. The operative time was longer, and the number of lymph nodes was higher in the extended right hemicolectomy group (p<0.001). Conclusion: We have shown that segmental resection of the splenic flexure is surgically and clinically suitable for the adequate management of operable cases of carcinoma of the splenic flexure. (AU)

RNA-binding proteins RBM-HuR, RBM3 and PODXL expression in urothelial carcinoma of the urinary bladder. Prognostic and clinical implications.

AIM OF THE STUDY: The clinical significance and predictive and prognostic value of HuR, RBM3, and PODXL expression in patients with urothelial bladder cancer (UBC) are not clear yet. The aim of this study was to assess HuR, RBM3 and PODXL expression in muscle invasive and non-muscle invasive UBC tissues, and to investigate the clinicopathological correlations and their predictive and prognostic impact in patients with such type of cancer. MATERIAL AND METHODS: RBM-HuR, RBM3 and PODXL expression levels were evaluated in 70 patients with urothelial carcinoma by immunohistochemistry. The relationships between their expression, clinicopathological findings and prognostic data were analyzed. RESULTS: High RBM-HuR expression was related to muscle invasion (p = 0.008), metastasis to lymph nodes (p = 0.007), and presence of blood spread (p = 0.049). High RBM3 expression was associated with lower grade (p = 0.044), absence of distant metastasis (p = 0.025), and absence of lymph node metastasis (p = 0.018). High PODXL expression was significantly associated with advanced tumor stage (p < 0.001), larger tumor size (p = 0.050), lymphovascular invasion (p = 0.006), lymph node metastasis (p = 0.008), higher grade (p = 0.043) and distant metastasis (p = 0.002).Three-year overall survival rate was negatively associated with high expression of both RBM-HuR and PODXL while it was directly correlated with high expression of RBM3 (p = 0.008, 0.009 and 0.015 respectively). High RBM-HuR and PODXL expression and low expression of RBM3 were related to tumor recurrence (p = 0.022, 0.011 and 0.015). CONCLUSIONS: RBM-HuR and PODXL expressions are markers of poor prognosis while RBM3 is a good prognostic marker for urothelial carcinoma of the bladder.

Clinico-pathological and prognostic implications of Srx, Nrf2, and PROX1 expression in gastric cancer and adjacent non-neoplastic mucosa - an immunohistochemical study.

INTRODUCTION: Sulfiredoxin (Srx), which is an endogenous antioxidant substance which could, regulate the signaling pathways of reactive oxygen species. Nuclear factor erythroid 2-related factor 2 (Nrf2) is Cap-N-collar (CNC) transcription factors family member that have essential roles in regulation of antioxidant response. The transcription factor PROX1 is a transcription factor and a key regulatory protein in cancer development. AIM OF THE STUDY: To analyze levels of tissue expression of Srx, Nrf2, and PROX1 in gastric cancer and adjacent non-neoplastic gastric mucosa to clarify the relationship between their expression levels, clinical, pathological parameters and patients' outcome. The results might lead to discovering novel targeted therapies to gastric cancers. MATERIAL AND METHODS: We included 70 paraffin-embedded samples: 50 specimens from gastric carcinomas and 20 specimens from adjacent non-neoplastic gastric mucosa. All samples are stained with Srx, Nrf2, and PROX1 using immunohistochemistry, correlated their expression with clinicopathological and prognostic parameters of patients. RESULTS: High levels of Srx and Nrf2 expression were positively associated with higher cancer grade (p = 0.006, 0.031 respectively), advanced stage (p < 0.001, 0.02 respectively), higher incidence of distant metastases (p = 0.029, 0.03 respectively) and dismal outcome (p < 0.001). High levels of PROX1 expression were associated with lower cancer grade (p = 0.005), absence of lymph nodes metastases (p = 0.023), early stage (p = 0.003), absence of relapse (p = 0.004), and favorable outcome (p < 0.001). CONCLUSIONS: Srx and Nrf2 expression increase gastric cancer invasiveness, suggesting their utility as poor prognostic markers, but PROX1 serves as a favorable prognostic marker of gastric cancer patients.