Magdy M. Saber

Protumorigenic role of Timeless in hepatocellular carcinoma

The mammalian timeless (TIM) protein interacts with proteins of the endogenous clock and essentially contributes to the circadian rhythm. In addition, TIM is involved in maintenance of chromosome integrity, growth control and development. Thus, we hypothesized that TIM may exert a potential protumorigenic function in human hepatocarcinogenesis. TIM was overexpressed in a subset of human HCCs both at the mRNA and the protein level. siRNA-mediated knockdown of TIM reduced cell viability due to the induction of apoptosis and G2 arrest. The latter was mediated via CHEK2 phosphorylation. In addition, siRNA-treated cells showed a significantly reduced migratory capacity and reduced expression levels of various proteins. Mechanistically, TIM directly interacts with the eukaryotic elongation factor 1A2 (EEF1A2), which binds to actin filaments to promote tumor cell migration. siRNA-mediated knockdown of TIM reduced EEF1A2 protein levels thereby affecting ribosomal protein biosynthesis. Thus, overexpression of TIM exerts oncogenic function in human HCCs, which is mediated via CHEK2 and EEF1A2.

Gastric carcinoma at Tanta Cancer Center: A comparative retrospective clinico-pathological study of the elderly versus the non-elderly

BACKGROUND AND AIMS To study the clinico-pathological features, treatments and outcomes of gastric carcinoma (GC) in the elderly (⩾65 years) and the non-elderly Egyptian patients. METHODS This retrospective cohort study included 168 patients with histologically confirmed GC treated at Tanta Cancer Center between 2003 and 2007. RESULTS Compared to the non-elderly, elderly patients had significantly higher proportion of tumors involving the cardia (p=0.034) and of adenocarcinoma NOS histology (p=0.032). Treatments were largely comparable in the two groups. Response to palliative chemotherapy was achieved in 44.4% of the elderly and 25.5% of the non-elderly patients (p=0.417). The median overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 6, 17 and 3 months, respectively. The median OS was 4 months in the elderly compared to 9 months in the non-elderly (p=0.005). The median DFS was 4 months in the elderly compared to 20 months in the non-elderly (p=0.004). The median PFS was 2 months in the elderly compared to 3 months in the non-elderly (p=0.685). In multivariate analysis, poor performance status was an independent predictor of poor OS, DFS and PFS. Non-curative or no surgery and lack of chemotherapy use were independent predictors of poor OS. Age was an independent predictor of poor DFS. CONCLUSIONS Compared to the non-elderly, GC in the elderly has similar clinico-pathological characteristics and exhibits comparable outcomes with the same treatment options. Treatments should be tailored to each patient.

Primary gastrointestinal lymphoma in an Egyptian district: a study using a population-based cancer registry.

INTRODUCTION Gastrointestinal lymphoma (GIL) is the most common extranodal form of non-Hodgkins lymphoma (NHL) with geographical and age variation of its various subtypes. AIM To study GIL in Gharbiah, Egypt and to recognize the treatments employed and their outcomes including survival. METHODS This is a retrospective study. Between 2000 and 2002, 40 adult patients with GIL were identified in the Gharbiah population based cancer registry (GPBCR); 26 cases of whom were treated at Tanta Cancer Center (TCC). RESULTS GIL in Gharbiah, Egypt represented 6.2% of all GIT cancers. The median age was 47 years with slight male predominance. The commonest primary site was the stomach followed by the colon/rectum then the small intestine (67.5%, 25% and 7.5%, respectively). The commonest histological subtypes were the diffuse large B-cell (41.5%) followed by marginal zone B-cell (39%). The commonest symptoms were abdominal pains followed by vomiting. Only 18% of GILs were surgically resected. Most patients (77%) received chemotherapy with a 60% complete response (CR) rate. Once in CR, relapses are occasional. The median overall survival (OS) and progression free survival (PFS) were 31 and 14 months (95% CI, 13.2-48.7 and 6.4-21.6 months, respectively). Gastric primary site and diffuse large B cell subtype carry a non-significant worse OS and PFS than those of other sites and subtypes. CONCLUSIONS GILs in Gharbiah, Egypt are characterized by predominance of male gender, gastric site and marginal zone histology. Survival is worse for gastric and diffuse large B-cell GILs compared to other sites and histologies.

Treatment outcomes of female germ cell tumors: The Egyptian National Cancer Institute experience

INTRODUCTION Female germ cell tumors (GCTS) are rare tumors that carry a good prognosis. AIM To report the experience of the Egyptian National Cancer Institute (ENCI) in managing female GCTs. METHODS This retrospective study included 19 females with ovarian GCTs presenting to the ENCI between 2006 and 2010. RESULTS The median age was 23years. Ovaries were the primary site in all patients. Dysgerminoma and teratoma were the predominant pathologies followed by mixed GCT in females. Unilateral ovariectomy or ovarian tumorectomy were the classic surgical procedures with R0 resection being feasible in most cases. Surveillance was adopted in six patients with stage I disease. Chemotherapy was administered in 63% of ovarian GCTs with BEP being the commonest regimen with reasonable tolerability and good response rates. The median OS and EFS were not reached. The projected 5-year OS rate was 93.8%. Both OS and EFS were better in patients responding to chemotherapy than non-responders (p<0.002). Stage of disease did not significantly affect OS or EFS. CONCLUSIONS Female GCTs rarely affect Egyptian females. They have good prognosis.

Role of Ki67 in predicting resistance to adjuvant tamoxifen in postmenopausal breast cancer patients.

INTRODUCTION Breast cancer (BC) is a major health problem in Egypt and worldwide. Its prognosis depends not only on tumor stage but also on tumor biology. AIM To correlate the expression of Ki67 with the clinical outcomes of early hormone-receptor positive postmenopausal BC patients who are receiving tamoxifen. METHODS This cohort study included 70 patients. They were followed up for a minimum of 2 years. Ki67 was assessed on paraffin-embedded blocks using immunohistochemistry methods. RESULTS The median Ki67 value was 22.5% (IQR, 10%-50%). Ki67 was significantly higher in patients with HER2 positive tumors compared to HER2 negative tumors. After a median follow up period of 53 months, 22 patients (31%) developed disease recurrence either loco-regional or distant in 5.7% and 30%, respectively. Recurrent patients had significantly higher tumor stage, nodal stage and Ki67 values compared to non-recurrent cases. The 2-, 3- and 5-year overall survival (OS) and disease-free survival (DFS) rates were 100% & 91%, 98% & 84% and 77% & 59%, respectively. DFS was significantly worse with higher TNM stage, lower ER expression and higher Ki67 values. OS was significantly worse in patients with Ki67 values ≥ 30%. Ki67 ≥ 30% was an independent predictor of recurrence, poor DFS and OS. CONCLUSION High Ki67 expression is predictive of poor prognosis and of resistance to adjuvant tamoxifen therapy in postmenopausal BC. We recommend considering Ki67 as one of the risk factors that guide adjuvant treatment decisions.

Small intestinal cancers among adults in an Egyptian district: A clinicopathological study using a population-based cancer registry☆

BACKGROUND Small intestinal cancers (SICs) are very rare all over the world and little is known about them in Egypt. METHODS This a retrospective study. Between 2000 and 2002, 30 cases with SICs were identified in the Gharbiah population based cancer registry (GPBCR); 17 cases of whom were treated at Tanta Cancer Center (TCC). RESULTS The median age was 51 years with female predominance. The duodenum was the commonest site (43%) followed by the ileum then the jejunum. Adenocarcinoma (AC), carcinoids, gastrointestinal stromal tumors (GISTs), lymphoma and sarcoma represented 50%, 10%, 17%, 13% and 10% respectively. Abdominal pain was the commonest symptom and localized disease was the commonest presentation. Surgery, chemotherapy and radiotherapy were employed in 65%, 35% and 0% of patients, respectively. The median overall survival and progression free survival (OS, PFS) were 18 and 15 months (95% CI: 10.4-25.6 and 3.6-26.4), respectively. AC had inferior OS and PFS to other histologies (p = 0.08 and 0.12, respectively). Also, duodenum subsite was inferior in OS and PFS to other sites (p = 0.25 and 0.35, respectively). CONCLUSIONS SICs in Gharbiah, Egypt are characterized by predominance of female gender and adenocarcinoma histology. One year survival is 64% with a poor outcome for adenocarcinoma and duodenal subsite.