Iman Gouda

Detection of Hepatocellular Carcinoma Using Glycomic Analysis

Purpose: Hepatocellular carcinoma (HCC) represents an increasing health problem in the United States. Serum α-fetoprotein, the currently used clinical marker, is elevated in only ∼60% of HCC patients; therefore, the identification of additional markers is expected to have significant public health impact. The objective of our study was to quantitatively assess N-glycans originating from serum glycoproteins as alternative markers for the detection of HCC. Experimental Design: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for quantitative comparison of 83 N-glycans in serum samples of 202 participants (73 HCC cases, 77 age- and gender-matched cancer-free controls, and 52 patients with chronic liver disease). N-glycans were enzymatically released from serum glycoproteins and permethylated before mass spectrometric quantification. Results: The abundance of 57 N-glycans was significantly altered in HCC patients compared with controls. The sensitivity of six individual glycans evaluated for separation of HCC cases from population controls ranged from 73% to 90%, and the specificity ranged from 36% to 91%. A combination of three selected N-glycans was sufficient to classify HCC with 90% sensitivity and 89% specificity in an independent validation set of patients with chronic liver disease. The three N-glycans remained associated with HCC after adjustment for chronic viral infection and other known covariates, whereas the other glycans increased significantly at earlier stages of the progression of chronic viral infection to HCC. Conclusion: A set of three identified N-glycans is sufficient for the detection of HCC with 90% prediction accuracy in a population with high rates of hepatitis C viral infection. Further evaluation of a wider clinical utility of these candidate markers is warranted.

Urinary Bladder Cancer Risk Factors in Egypt: A Multicenter Case–Control Study

Background: We investigated associations between tobacco exposure, history of schistosomiasis, and bladder cancer risk in Egypt. Methods: We analyzed data from a case–control study (1,886 newly diagnosed and histologically confirmed cases and 2,716 age-, gender-, and residence-matched, population-based controls). Using logistic regression, we estimated the covariate-adjusted ORs and 95% confidence interval (CI) of the associations. Results: Among men, cigarette smoking was associated with an increased risk of urothelial carcinoma (OR = 1.8; 95% CI, 1.4–2.2) but not squamous cell carcinoma (SCC); smoking both water pipes and cigarettes was associated with an even greater risk for urothelial carcinoma (OR = 2.9; 95% CI, 2.1–3.9) and a statistically significant risk for SCC (OR = 1.8; 95% CI, 1.2–2.6). Among nonsmoking men and women, environmental tobacco smoke exposure was associated with an increased risk of urothelial carcinoma. History of schistosomiasis was associated with increased risk of both urothelial carcinoma (OR = 1.9; 95% CI, 1.2–2.9) and SCC (OR = 1.9; 95% CI, 1.2–3.0) in women and to a lesser extent (OR = 1.4; 95% CI, 1.2–1.7 and OR = 1.4; 95% CI, 1.1–1.7, for urothelial carcinoma and SCC, respectively) in men. Conclusions: The results suggest that schistosomiasis and tobacco smoking increase the risk of both SCC and urothelial carcinoma. Impact: This study provides new evidence for associations between bladder cancer subtypes and schistosomiasis and suggests that smoking both cigarettes and water pipes increases the risk for SCC and urothelial carcinoma in Egyptian men. Cancer Epidemiol Biomarkers Prev; 21(3); 537–46. ©2011 AACR.

Estrogen exposure and bladder cancer risk in Egyptian women

OBJECTIVE To examine associations between reproductive history and urinary bladder cancer in Egyptian women. METHODS We used questionnaire data from an ongoing, multicenter case-control study in Egypt. Controls were matched on age and residence area. This analysis focused on female cases with confirmed urothelial (UC) and squamous cell (SCC) carcinoma of the bladder. RESULTS We recruited 779 women (540 controls, 239 cases; >98.0% nonsmokers). Younger age at menopause (<45 y) and older age at first pregnancy (>18 y) were factors significantly associated with increased risk of bladder cancer, even after adjusting for schistosomiasis history and other covariates in the multivariable logistic model; adjusted odds ratio and 95% confidence intervals were 1.98 (1.41, 2.77) and 6.26 (3.46, 11.34), respectively. On the other hand, multiple pregnancies or use of oral contraceptives were associated with decreased odds of having bladder cancer. Similar associations were observed with UC and SCC when analyzed separately; however, the magnitude of association with SCC was lower than with UC. CONCLUSION Our data suggest that early estrogen exposure, or the relative lack of it, plays a role in urinary bladder carcinoma development among Egyptian women.

Schistosomiasis and bladder cancer: similarities and differences from urothelial cancer

Through the years, schistosoma-associated bladder cancer was believed to be a unique entity of disease, different from urothelial cancer. As carcinogenesis is a highly complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation and regulation process, confirmation of their minute differences or similarities are extremely difficult. In bladder cancer, many of these carcinogenic cascades were not fully documented in spite of the efforts undertaken. The control of schistosomiasis and the subsequent decrease in the intensity of infestation showed feature changes approaching that of urothelial tumors. However, schistosoma-associated bladder cancer still presents in more advanced stages than schistosoma-non-associated urothelial cancer. Furthermore, many data were collected proving that, upon applying the same treatment protocol and management care, stage-by-stage comparison of the treatment end results were found to be similar in bladder cancer patients with the different etiologies.

Immunohistochemical Detection of Hepatitis C Virus (Genotype 4) in B-cell NHL in an Egyptian Population: Correlation With Serum HCV-RNA

Background and AimRetrospective evaluation of hepatitis C virus (HCV) prevalence in lymphoma tissues has important applications in clarifying the contribution of viral factors to the pathogenesis. Trials for detection of HCV at the cellular level in lymphoma tissues are, so far, minimal with unsatisfactory results. We aimed to study the detection and localization of HCV in the tissues of B-cell non-Hodgkin lymphoma (NHL) patients. DesignWe performed immunohistochemistry to detect the HCV nonstructural 3 protein in paraffin-embedded tissue specimens of B-cell NHL patients, in 39 serum HCV-RNA positive samples and 35 serum HCV-RNA negative samples as controls. The serum analysis was carried out for HCV antibodies using enzyme-linked immunoassay and for HCV-RNA using reverse transcription-polymerase chain reaction. Reverse transcription-polymerase chain reaction was used to detect the HCV-RNA in tissues in immunohistochemically positive cases. We correlated the results with the clinicopathologic characteristics of the patients. ResultsA diffuse cytoplasmic immunohistochemical staining for HCV in the lymphoid cells was detected in 8 of 39 serum positive cases (20.5%), all of which were genotype 4, which is the most prevalent HCV genotype in Egypt. Only 2 out of 35 serum negative control samples showed positive staining and in 1 of them HCV-RNA was detected in tissue. No significant correlation was detected between HCV positive cases and the clinicopathologic features of the patients. ConclusionsImmunohistochemical detection of HCV proteins in lymphoma tissues supports a potential role of viral replication in lymphomagenesis. The low number of cases showing expression of viral proteins may represent a low viral load in lymphoid tissue and/or restriction of HCV protein expression to certain subtypes of B-cell NHL. Immunohistochemistry can be used as a complementary tool for specific HCV detection in the paraffin-embedded material of lymphoma tissues not suitable for RNA analysis.

Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt.

OBJECTIVES To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men. MATERIALS AND METHODS We used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively. RESULTS The study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n = 169), and 527 controls. The odds of having either type of bladder cancer were lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0.34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women. CONCLUSIONS These findings suggest that even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared with women in South Egypt.

Epidemiology and management of breast carcinoma in Egyptian males: experience of a single Cancer Institute.

OBJECTIVE To assess the epidemiological and clinico-pathological features, surgical and reconstructive techniques, adjuvant treatments and clinical outcome of breast carcinoma in males (BCM) at the Egyptian National Cancer Institute (NCI). PATIENTS AND METHODS Thirty-two males with breast carcinoma presented to NCI between January 2000 and December 2002. They were evaluated by complete history, physical examination, laboratory and radiological investigations. RESULTS Median age was 59 years. Left sided and retroareolar breast lumps were the commonest presentations. Grade II tumors positive for hormone receptors were very common. Stages I, II, III and IV of the disease were encountered in 6.2%, 34.4%, 34.4% and 25.0% of patients, respectively. Curative surgery was done in 22 patients; they received adjuvant hormonal therapy, chemotherapy and radiotherapy in 22, 16 and 10 patients, respectively. Eight metastatic patients were treated with palliative measures. Surgery was done in 25 patients; the most common procedure was modified radical mastectomy (40.6%). Primary closure was feasible in 17 patients (68%), local flaps were needed in 4 cases (16%), while myocutaneous flap was done in 3 cases (12%). The commonest complication was the development of seroma (9 cases). The overall survival (OS) at 5 years was 65.4%. The disease free survival (DFS) at 5 years was 53.9%. Stage and curative surgery significantly affected OS, while type of surgery was the only variable significantly affecting DFS. CONCLUSION Male breast carcinoma occurs at older ages than females, usually in advanced stage. This necessitates directing attention of males and awareness on the prevalence and risk factors for this disease.

Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian

Although it is widely recognized that telomere dysfunction plays an important role in cancer, the relationship between telomere function and bladder cancer risk is not well defined. In a case-control study of bladder cancer in Egypt, we examined relationships between two telomere features and bladder cancer risk. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and the risk of urothelial carcinoma of the bladder. High telomere length variation (TLV) across all chromosomal ends was significantly associated with an increased risk of bladder cancer [adjusted odds ratios (OR) = 2.22, 95% confidence interval (CI) = 1.48-3.35], as was long average telomere length (OR = 3.19, 95% CI = 2.07, 4.91). Further, TLV and average telomere length jointly affected bladder cancer risk: when comparing individuals with long telomere length and high TLV to those with short telomere length and low TLV, the adjusted OR was 14.68 (95% CI: 6.74-31.98). These associations were stronger among individuals who are 60 years of age or younger. In summary, long and heterogeneous telomere length in blood lymphocytes was strongly associated with an increased bladder cancer risk in Egyptian and the association was modulated by age.

Bladder Cancer and Schistosomiasis: Is There a Difference for the Association?

Bladder cancer represents a significant worldwide health problem with an estimated 386,300 new cases and 150,200 deaths in 2008 worldwide. The majority of bladder cancer occurs in males and there is a 14-fold variation in incidence internationally. The highest incidence rates are found in the countries of Europe, North America, and Northern Africa (Jemal et al.2011). Smoking and occupational exposures are the major risk factors in Western countries, whereas chronic infection with Schistosoma hematobium (SH) in developing countries, particularly in Africa and the Middle East, accounts for about 50% of the total burden. The majority of bladder cancers associated with schistosomiasis are squamous cell carcinoma (Figure 1). Although the majority of bladder cancers, present with disease confined to the superficial layer of the bladder wall, approximately 20–40% of the patients will present with or subsequently develop invasive cancer. Bladder cancer is morphologically heterogeneous; more than 90 % of bladder cancer cases are urothelial (UC, transitional cell, TCC) carcinoma, whereas primary squamous cell carcinoma (SCC), adenocarcinoma, small cell carcinoma and other rare tumors are less common (Lopez-Beltran and Cheng, 2006). Urothelial cell carcinoma can present mixed with other malignant components (figure 2). These mixed forms of bladder histologies include squamous differentiation (present in 20 60% of bladder cancer cases), adenocarcinoma or glandular differentiation (10%), sarcomatoid (7%), micropapillary (3.7%) and lymphoepitelioma-like carcinoma. About 1 in 25 Western men and 1 in 80 women will be diagnosed with bladder cancer (BC) sometime in their life. In many developing countries, life expectancy is much lower than Westerns, which is one of the reasons why overall BC incidence (not age-specific incidence) is lower in these developing countries (Albertson and Pinkel, 2003). It is associated with substantial morbidity and mortality. History of Tobacco smoking not only increases the incidence of BC, but also it can increase the tumor grade, its size and the number of tumor lesions (Muscheck et al, 2000). Chronic schistosomal cystitis was related for a long period to the development of BC in areas endemic for schistosomiasis like Egypt. In these areas, risk factors are many, including exposure to schistosomiasis, increased smoking rate and exposure to carcinogenic chemicals (Kallioniemi et al, 1992).