Original articleExpression of c-erb-B2 gene in bladder cancer of Egyptian patients and its correlation with p53 and bcl-2
Introduction
Urinary bladder cancer (UBC) is the 9th most common type of cancer and the 13th most common cause of death worldwide. The highest incidence rates of UBC were found in Europe, United States, and Egypt [1]. The age standardized rates of UBC are 16.9/100,000 (in more developed countries) and 5.3/100,000 (in less developed countries) compared to 21.1/100,000 in Egypt. In Egypt, UBC is one of the most common malignancies in males and ranked 2nd among them [2]. Urinary bladder cancer rates in men are three to four times than those in females [3]. The two main histological types of UBC are urothelial or transitional cell carcinoma (TCC) and squamous cell carcinoma (SCC). The other varieties represent small percentage i.e. less than 5–10% [4].
The tumor suppressor protein p53 is a key regulator of the cellular response to genotoxic damage, and thus plays a pivotal role in preventing cancer formation. Once DNA damage has been incurred, p53 can elicit several different responses to either correct the error(s) or destroy the damaged cell. First, p53 can induce the first growth phase cell cycle arrest, which stops the cell from dividing and allows time to repair the damage before the DNA is replicated. Second, p53 can activate DNA repair proteins to derive the repair of damaged DNA. Third, as a last resort, p53 can induce damaged cells to undergo apoptosis, thereby eliminating damaged and potentially dangerous cells at risk for neoplastic transformation. Due to its critical importance in maintaining genetic stability, p53 has been called the “gatekeeper” or “guardian” of genome [5]. The bcl-2 family proteins are the most important regulators of the mitochondrial pathway of apoptosis [6]. bcl-2 family proteins are divided into three subfamilies, bcl-2, bcl-2-associated X protein (Bax)/bcl-2 homologous antagonist killer (Bak) and BH3-only subfamilies [7]. bcl-2 subfamily proteins have BH1, 2 and 3 and promote cell survival (anti-apoptotic bcl-2 family). Bax/Bak subfamily proteins have BH1, 2 and 3 and are pro-apoptotic. BH3-only subfamily proteins are also pro-apoptotic and function as inhibitors of anti-apoptotic bcl-2 family proteins or activators of Bax/Bak.
The human epidermal growth factor (HER2, also known HER2/Neu or c-erb-B2) gene is located on the chromosome 17q. It is a proto-oncogene, a normal gene with potential to become an oncogene as a result of molecular alterations such as mutation, amplification or overexpression of its protein product [8]. It encodes a transmembrane growth factor receptor with tyrosine kinase activity that is a member of the epidermal growth factor receptor family [9]. The HER2/neu-encoded protein molecule occupies a critical position in the biochemical pathways responsible for the transduction of mitogenic signals from a variety of growth factor receptors. In addition to its role in regulating normal cellular proliferation, overexpression of the HER2/neu gene appears to play a role in neoplastic cell growth [10]. C-erb-B2 amplification and/or overexpression was detected in a variety of human cancers including bladder cancer [11], [12], [13]. The present work was performed to assess C-erbB-4 oncogene amplification by PCR technology in bladder cancer and its correlation with p53 and bcl-2.
Section snippets
Patient groups
This study included 40 urinary bladder cancer patients obtained from Pathology Department, National Cancer Institute, Cairo University. The study met the criteria of the Ethics committee of the institution. The patients were divided into two groups:
Clinical data
Clinical data related to the selected cases were obtained from the patients’ medical records
Clinicopathological data
The total number of specimens used in the present study was 40 specimens, 20 transitional cell carcinoma and 20 squamous cell carcinoma. The mean ages of TCC and SCC were 46.4 ± 5.5 and 45.4 ± 6.6 years, respectively. The mean tumor sizes of both TCC and SCC were 2.35 ± 0.8 and 2.21 ± 0.5 cm, respectively. In TCC group (20 specimens), 16 specimens (80%) were in grade 2 while only 4 specimens (20%) were in grade 3. Concerning the SCC group (20 specimens), 15 specimens (75%) were in grade 2 while only 5
Discussion
Urinary bladder cancer is the most common malignancy of the urinary tract [15]. In Egypt based on the results of National Population-Based Registry Program 2008–2011, the UBC is the 3rd most frequent cancer in both sexes. It ranked 2nd in males after liver cancer and represented 10.71% [2].
In the present study, no significant difference was recorded between the ages of TCC and SCC groups. Zaghloul et al. [4] reported an increase of age with time in TCC cases from 54.2 ± 9.5 in period 1988–1993 to
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