Prognostic significance of cyclooxygenase-2, epidermal growth factor receptor 1, and microvascular density in gastric cancer.

Gastric cancer remains a significant global health burden with poor treatment outcome. New treatment modalities that target inflammation, proliferation, and angiogenesis have been used in various cancers, including gastric cancer. We sought to study the pattern of expression of two important proteins, cyclooxygenase-2 and epidermal growth factor receptor, and their association with microvascular density, clinicopathological features, and survival in Arab Omani patients with gastric cancer. Formalin-fixed, paraffin-embedded tumors were studied by immunohistochemistry using monoclonal antibodies to cyclooxygenase-2, epidermal growth factor receptor, and CD34. The immunohistochemical results were correlated with clinicopathological features and survival. In our study population, we found a male/female ratio of 72:43, a median age of 59 years, stage III and IV incidence of 66.9%, and a median follow-up of 96 months. Positive expression rates of cyclooxygenase-2 and epidermal growth factor receptor were 89.6 and 23.5%, respectively. The median microvascular density value was 52.5. When this value was determined as the cut-off point, 50% of patients were found to have high microvascular density. Epidermal growth factor receptor over-expression correlated with high microvascular density values, advanced lymph node involvement (N3), and TNM stage presentation (III and IV). Similarly, lymph node involvement was associated with cyclooxygenase-2 over-expression and high microvascular density. Univariate analysis showed that epidermal growth factor receptor over-expression, pathological T3 and T4 disease, and overall stage III and IV disease were adverse prognostic factors. On multivariate analysis using a Cox regression model, expression of epidermal growth factor receptor, and advanced TNM stage were significant adverse prognostic factors for overall survival. Expression of epidermal growth factor receptor in Arab Omani patients with gastric cancer correlates with aggressive tumor characteristics and is an independent prognostic factor. Further clinical studies are needed to evaluate the utility of epidermal growth factor receptor immunohistochemistry as a tool for gastric cancer treatment.

The prognostic determinants of gastric cancer treatment outcome in Omani Arab patients.

BACKGROUND: Gastric cancer is the most common cancer in Oman and a leading cause of cancer death. The variation in survival rates between countries and ethnic groups has been attributed to early detection policies, differences in clinicopathological features, treatment approaches, and biological characteristics. There were no previous reports on gastric cancer from Oman and very few studies on Asian Arabs. AIM: To evaluate the impact of clinicopathological and treatment variables on the survival prospects of Omani Arab patients diagnosed with gastric cancer. METHODS: The medical records of 339 Omani Arab patients diagnosed with invasive gastric adenocarcinoma during the period 1993-2004 were retrospectively reviewed. The relative importance of clinicopathological features and surgical and medical treatments were assessed using univariate and multivariate analyses. RESULTS: Most patients had distal ulcerating-type gastric cancer and presented at advanced stages. The median survival time for the entire cohort was 12 months (95% CI 9.7-14.4) with a 5-year overall survival rate of 16.7%. On univariate analysis of 237 patients who underwent surgical resection, the following positive prognostic factors emerged as significant: early overall TNM stage, early T stage, negative lymph nodes, tumor size <5 cm, ulcerating macroscopic appearance, and curative surgical attempt. The independent prognostic factors on multivariate analysis were T stage and lymph node involvement. CONCLUSION: The overall T and N stages are the most important determining factor for survival in Omani Arab patients. More efforts need to be made for the early detection of gastric cancer in developing countries such as Oman, while continuing to employ the standard surgical and medical treatments.

The prognostic significance of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients.

BACKGROUND: The variability of prognosis within a pathological stage of gastric cancer (GC) at presentation, underscores the need for specific biological markers to identify subgroups of patients with aggressive course for intensive treatment. To our knowledge, this is the first study from an Arab population reporting on the relationship of p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67 expression, and clinicopathological features and their prognostic significance. METHODS: Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53, p27 kip1, p21 waf1, HER-2/neu, and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: M:F = 80:41; median age = 60 years; stage III and IV = 71%; and median follow-up = 34.4 months. Positive expression rates of p53, p27 kip1, p21 waf1, Ki67, and HER-2/neu were 54%, 40%, 8.3%, 70%, and 12% respectively. p53 expression correlated with age <60 years (P = 0.03), tumor size >5 cm (P = 0.01), p27 kip1 and Ki67 expression (P = 0.0001), and HER-2/neu (P = 0.04). p21 waf1 correlated inversely with T-stage (P = 0.008) and Her-2/neu expression correlated with histological grade (P = 0.04) and T-stage (P = 0.008). Univariate analysis showed that p53 overexpression (P = 0.01), fungating and infiltrative macroscopic appearance (P = 0.02), size >5 cm (P = 0.0001), lymph node metastasis (P = 0.0001), p T3 and T4 disease (P = 0.01), and overall stage III and IV (P = 0.0001) disease were adverse prognostic factors. Patients with tumor profiles p53 (-)/p27 (+) had better survival than those with p53 (+)/p27 kip1 (-)(P = 0.02). On multivariate analysis by Cox regression model, the expression of p53 (P = 0.03) and lymph node involvement (P = 0.01) were significant adverse prognostic factors for overall survival. CONCLUSIONS: The expression of p53 in Arab patients with GC correlates with aggressive tumor characteristics and is an independent prognostic factor. The combined analysis of p53 and p27 kip1 is of added prognostic value.

The outcome of treatment of breast cancer in a developing country--Oman.

The aim of the present study was to evaluate the outcome of treatment of breast cancer in Oman with an analysis of clinico-pathological features, treatment modalities utilized, and prognostic factors. One hundred fifty-two breast cancer patients diagnosed between January 1996 and June 2002 were evaluated retrospectively. Their mean age was 48.5 (S.D. +/- 10.8) years, and 48% of the female patients were premenopausal. The mean tumor size according to pathology was 4.6 (S.D. 3.29)cm, and 34.9% and 15.8% of patients had stage III or IV disease, respectively. Only 26.3% of the patients had breast-conserving surgery, and neoadjuvant chemotherapy was underutilized. The overall 5-year relapse-free survival (RFS) and overall (OS) survival rates were 62% and 64%, respectively. On multivariate analysis, axillary lymph node involvement and tumor differentiation were predictive of RFS and OS, respectively. Thus, breast cancer patients in Oman present with advanced stages of the disease at younger ages than their counterparts in the West and have lower survival rates. Increasing awareness and the introduction of screening programs and of a multidisciplinary approach are essential in Oman and other developing countries to improve the outcome of treatment.

Significance of p53, Bcl-2, and HER-2/neu protein expression in Omani Arab females with breast cancer.

Racial disparity in the presentation of breast cancer and the outcome of its treatment is well established. However, the causes remain unexplained. The scarcity of reports about the prognostic significance of p53, bcl-2, and HER-2/neu in Arab females with breast cancer has been the impetus to this study. We evaluated the prognostic significance of altered expression of p53, bcl-2, HER-2/neu in Omani Arab females with non-metastatic breast cancer with correlation to other established prognostic factors. We have retrospectively analyzed the immunohistochemical expression of p53, HER-2/neu and bcl-2 in paraffin embedded blocks of 72 females diagnosed with invasive breast cancer between 1992 and 2002. The expression of the above proteins was correlated with other prognostic factors and univariate and multivariate analysis was carried out for all prognostic factors. Overexpression of p53 significantly correlated with younger age (<40), pre-menopausal status, poor differentiation with inverse correlation with bcl-2 expression. Expression of bcl-2 immunopostivity significantly correlated to low histological grade and positive estrogen and progesterone receptor status. On univariate and multivariate p53 overexpression and lack of bcl-2 immunostaining resulted in worse survival outcome, but not Her-2/neu overexpression. Expression patterns of p53 and bcl-2 are independent predictors of survival in Omani Arab population which may help to stratify these patients into different risk groups.