The prognostic values of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms in Egyptian patients with acute lymphoblastic leukemia: A single-center study.

Background: Interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) genes contribute to oncogenesis. We evaluated the influence of the IL-10 (G1082A) and TNF-α (G308A) polymorphisms on the prognosis and outcomes of Egyptian patients with acute lymphoblastic leukemia (ALL). Materials and Methods: We investigated 64 children and 76 adults with ALL, between 2016 and 2019, for the IL-10 (G1082A) and TNF-α (G308A) polymorphisms using allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. Survival analyses were performed using the Kaplan-Meier estimator and the log-rank test. Results: In children with ALL, the A allele of TNF-α and IL-10 polymorphisms was associated with older age (P = 0.04 and 0.03), more extramedullary disease (P = 0.02 and 0.001), positive breakpoint cluster region-Abelson (BCR-ABL) rearrangement (p190; P = 0.04 and 0.001), and more relapse (P = 0.002). The IL-10 GG genotype was associated with higher overall survival in children (P = 0.026). Adults carrying the TNF-α A allele showed more extramedullary disease (P = 0.009) and relapse (P = 0.003). We also found a higher frequency of IL-10 A allele in adults with older age (P = 0.03), lower hemoglobin level (P = 0.04), positive BCR-ABL rearrangement (P = 0.001), more extramedullary disease (P = 0.001), more relapse (P = 0.002), and a longer time for the first complete remission (P = 0.003). Conclusion: A possible association exists between the A allele of IL-10 and TNF-α polymorphisms and poor prognosis in Egyptian patients with ALL, while the IL-10 GG genotype may be associated with better survival in children with ALL.

Expression of CD10 and CD15 in colorectal mucinous and signet ring adenocarcinomas and its relation to clinicopathological features and prognosis.

BACKGROUND: CD10 and CD15 expression has been reported in several tumors. Whether CD10 and CD15 have a role in colorectal mucinous and signet ring adenocarcinoma (MSA) tumorigenesis is not yet known. OBJECTIVE: We aimed to investigate the role of CD10 and CD15 expression in mucinous colorectal adenoma-carcinoma sequence (ACS) and determine if there is any clinical and prognostic significance associated with their expression. METHODS: Seventy-five cases of colorectal MSA, and 9 cases of adenoma samples were collected. Manual TMA blocks were constructed and immunohistochemistry for CD10 and CD15 was done. RESULTS: Compared to adenomas, CD15 expression was significantly higher in MSA (p= 0.002), in contrast to CD10 expression. CD15 positivity was significantly associated with microsatellite stable (MSS) tumors (p= 0.018). The association between CD10 positivity and fungating tumor growth showed marginal significance. Unlike CD10, CD15 positivity showed significant association with overall survival of colorectal MSA patients. CONCLUSIONS: CD15 expression seems to have a role in mucinous colorectal ACS, with significant impact on the survival of MSA patients. Further studies are suggested to identify any genetic alterations that may underlie a potential association with disease progression.

Prognostic significance of transforming growth factor ß receptor II in clinical stage III breast cancer patients - a pilot study.

BACKGROUND: Transforming growth factor-ß (TGFß) has a dual function in breast cancer, having a tumor suppressor activity in early carcinomas while enhancing tumor metastasis in advanced breast carcinoma. Consequently, the prognostic role of TGFß and its signaling cascade in breast cancer remain unclear. OBJECTIVE: To investigate the relationship between TßRII expression, clinic-pathological characteristics, and prognostic significance of TßRII expression in clinical stage III breast cancer. METHODS: Biopsy from the primary tumor was obtained from 30 newly diagnosed clinical stage III breast cancer patients before receiving any therapy. Expression of TßRII, ER, PR, Her2 and Ki-67 was assessed by immunohistochemistry. RESULTS: TßRII expression was positive in 66.7% of cases and was significantly associated with advanced nodal stage and distant metastases. After a median follow up of 42.3 months, TßRII was associated with poor disease-free survival and it was an independent factor for predicting the poor outcome for breast cancer patients, especially in node positive tumors, ER/PR positive and Her2-negative tumors. CONCLUSIONS: These findings suggest the usage of therapeutic drugs that target TGFß in advanced breast cancer patients may be effective. Nevertheless, blockage of the tumor promoting and sparing of the tumor suppressor effect of TGFß pathway should be taken into consideration. We suggest that these therapies might have more benefit in ER and PR positive tumors.

Clinical Impact of Breast Cancer Stem Cells in Metastatic Breast Cancer Patients.

BACKGROUND: Breast tumors are composed of phenotypically diverse groups of cells; however, it is unclear which of these cells contribute to tumor development. Breast cancer management usually targets proliferating cells, but as breast cancer stem cells are slowly cycling, they may escape these targets whenever they are not actively proliferating. This may explain the occurrence of recurrences and failure of the treatment. AIM: To assess the impact of the BCSC expression on progression-free survival (PFS), overall survival (OS), and tumor response in metastatic breast cancer patients and to correlate the BCSC expression with different clinicopathological parameters. MATERIAL: This prospective study enrolled 76 de novo metastatic breast cancer patients recruited from the Oncology Center, Mansoura University, Egypt, with a minimum age 31 years and a maximum of 70 years. Pretreatment BCSC markers (CD44 and CD24) were assessed by immunohistochemistry on formalin-fixed paraffin-embedded tumor tissues from a primary or metastatic site. Patients received different lines of treatment, hormonal or chemotherapy, according to their biological subtypes. Anti-Her2 was added for Her2-positive patients. RESULTS: Thirty-three patients (43.4%) were premenopausal and 43 patients (56.6%) were postmenopausal. Bone-only metastasis was seen in 12 patients (15.7%), however, visceral ± bone metastasis was seen in 64 patients (84.3%). BCSC markers (CD44+ve and CD24-ve) were expressed in 32 patients (42.1%), while 44 patients (57.9%) were not expressing BCSC markers. Out of 32 patients expressing BCSC, 22 patients (68%) were premenopausal and 28 patients (87.5%) were with high-grade (GIII) disease. BCSC was significantly presented in triple negative subtype breast cancer as there were 32 patients with the BCSC expression, and out of them, 15 patients (46.9%) had triple negative disease, 10 patients (31.3%) had luminal subtype, and seven patients (21.9%) were Her2-amplified, while there were 44 patients without BCSC expression, and out of them, 30 patients (68.2%) were of the luminal subtype, no patient (20.5%) had triple negative disease, and five patients (11.4%) were Her2-amplified (P 0.006). Twenty-four patients (31.5%) presented with visceral crisis; out of them, 17 patients (70.1%) were expressing BCSC which also denoted more aggressive disease. Seventy-four patients were candidates for the response assessment. BCSC-expressing patients showed poor response compared to non-BCSC (16.1% responsive versus 51.2%, respectively), with a significance relation (P 0.003). The BCSC expression was associated with both significant short PFS (median, 18 months vs. 35 months; P=0.001) and short OS (median, 26 months vs. 43 months; P=0.003). In multivariate analysis; BCSC expression was an independent prognostic factor for poor OS (P=0.055) along with the molecular subtype (P=0.012), Her2 status (P=0.011), and histologic grade (P=0.037). CONCLUSION: This study further validates the BCSC expression as a poor prognostic biomarker correlated with poor response, short PFS and OS. So, it could be used as a marker for tailoring treatment with different lines of therapies in further studies. The BCSC expression was highly presented in the triple negative subtype which is an aggressive disease that lacks different targets. So, targeting BCSC may carry a hope in future for this group of patients.

Prognostic Impact of Lymphoid Enhancer Factor 1 Expression and Serum Galectin.3 in Egyptian AML Patients.

BACKGROUND: Deregulation of the Wnt signaling pathway had a role in haematological malignancies. Previous studies reported that lymphoid enhancer factor 1 (LEF1) expression and serum Galectin-3 level could affect clinical parameters and outcome in acute myeloid leukemia patients, but as far as we know, no study has addressed their combined effect on AML patients. AIM: We studied the expression of LEF1 by real-time qPCR and measured serum level of Gal.3 by ELISA technique in peripheral blood of 69 AML patients and correlated it with different clinicopathological criteria of patients, response, PFS and OS. RESULTS: We found high expression (LEF1high) was associated with better OS (p = 0.02) and EFS (p = 0.019) compared to LEF1low, low serum Gal.3 level had better OS (p = 0.014) and EFS (p = 0.02) compared to high serum Gal.3 level. LEF1high less likely to carry a FLT3-ITD (p = 0.047) compared to LEF1low patient, also LEF1high characterized by favorable risk (p = 0.02) than LEF1low patients. While patients with higher Gal-3 levels characterized by poor risk (p = 0.02) than lower Gal.3 lels, also more likely to carry a FLT3-ITD with borderline significance (p = 0.054). Combined LEF1high/Gal.3 low patients had lower baseline blast percentages (p = 0.02), favorable risk (p = 0.01), less likely to carry FLT3-ITD (p = 0.02), higher CR rate (p = 0.055), shorter time to CR (0.001) than other groups. Among high Gal.3 level group, LEF1highexpression improved OS and EFS (20 and 15 months respectively) vs LEF1low expression (13 and 8 months respectively). CONCLUSION: We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level.