Expression and significance of p 53 and mdm 2 in atypical intestinal metaplasia and gastric carcinoma

Subtypes of intestinal metaplasia may have different manifestations in the carcinogenesis of gastric mucosa. The present study aimed to investigate expression of murine double minute gene 2 (mdm2) in atypical intestinal metaplasia (AIM) and its relationship to gastric carcinoma. Intestinal metaplasia (IM) specimens were obtained from 58 cases. Using a novel classification of IM, the specimens were classified according to morphological changes exhibited in the gastric mucosa; specifically, atypical intestinal metaplasia (AIM) and simple intestinal metaplasia (SIM). The gatric carcinoma specimens were then compared with types I, II and III IM based on different substances present in the mucous. Envision immunohistochemical technique was applied to the detection of the expression of p53 and mdm2 in 58 IM and 30 gastric carcinoma cases. Expression of both p53 and mdm2 proteins was found to be higher in gastric carcinomas (p53, 56.67%, 17/30 and mdm2, 53.33%, 16/30) and AIM (p53, 51.85%, 14/27 and mdm2, 51.85%, 14/27) as compared to SIM (p53, 25.81%, 8/31 and mdm2, 19.35%, 6/31) (P<0.05). A similar pattern of expression of mdm2 protein was found in type I (36.84%, 7/19), type II (38.46%, 10/26) and type III (23.08%, 3/13) IM and gastric carcinoma (53.33%, 16/30). p53 expression was higher in gastric carcinoma (56.67%) compared to type I IM (26.32%) (P<0.05). However, no differences were evident among type II (42.31%, 11/26), type III (46.15%, 6/13) IM and gastric carcinoma. AIM may reveal the precancerous nature of gastric carcinoma more clearly than SIM or the conventional IM subtypes. Additionally, AIM may be involved as a preneoplastic lesion and therefore be an effective indicator in the clinical follow-up of gastric carcinoma patients. Introduction Gastric carcinoma is the fourth most prevalent malignancy worldwide (1) and is one of the most common causes of cancer-related mortality in China (2). The only effective way of improving the survival rate of patients suffering from gastric carcinoma is an early diagnosis. More than half of patients presenting with gastric carcinoma diagnosed from a biopsy were in an advanced stage of cancer progression. Thus, a more critical understanding of preneoplastic lesions in the gastric mucosa may prove helpful in the detection of early-stage carcinoma in a clinical setting. The development of gastric carcinoma is closely associated with the presence of atrophic gastritis as well as intestinal metaplasia (IM). Furthermore, it has been shown that the presence of IM significantly increases the risk of gastric carcinoma (3). However, not all individuals with intestinal metaplasia progress to gastric cancer. Therefore, the issue as to which IM patients should be clinically followed has yet to be resolved (4). Three types (I-III) of IM have been described according to morphology and mucin histochemistry (5,6). Findings of a number of studies revealed that type III was closely involved in intestinal gastric carcinoma (7-10), whereas investigations that have been conducted conclude that sulphomucin-positive IM does not identify a high-risk group and is of no value in the surveillance of gastric cancer (11). Additionally, Petersson et al suggest that type III IM is a less sensitive indicator of future development of gastric carcinoma than previously anticipated (12). As in our previous study, in this study IM was divided into two subtypes according to morphology of the metaplastic epithelium: simple intestinal metaplasia (SIM), in which no or minimal polymorphism was found and atypical intestinal metaplasia (AIM), in which metaplastic cells presented significantly more polymorphisms or atypical changes (13). The predominant feature of AIM is the appearance of immature goblet cells scattered in the epithelium of IM already present in the gastric mucosa. These cells exhibit an enlarged cell nucleus with several mucin vacuoles in the cytoplasm and the nucleus loses its polarity. As with the immature goblet cells, changes are also observed in some columnar cells. In contrast, no or minimal nuclear pleomorphism and polarity change of goblet and columnar cells in SIM has been observed. The key to distinguishing the two groups of IM Expression and significance of p53 and mdm2 in atypical intestinal metaplasia and gastric carcinoma LIN WANG1,2, XIAO-YING ZHANG1, LING XU1, WEN-JUN LIU1, JUAN ZHANG2 and JIAN-PING ZHANG1,2 1Department of Pathology, Shandong University School of Medicine; 2Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China Received January 14, 2011; Accepted April 5, 2011 DOI: 10.3892/ol.2011. 292 Correspondence to: Dr Jian-Ping Zhang, Department of Pathology, Shandong University School of Medicine, Jinan, Shandong 250012,