【作者】 王宁博；

【导师】 王立东；

【作者基本信息】 郑州大学 ， 消化内科， 2005， 硕士

【摘要】 河南林州市(原林县)是世界上食管癌(Esophageal squamous cell carcinoma,SCC)和贲门癌(Gastric Cardia Adenocarcinoma,GCA)发病率和死亡率最高的地区,目前仍是该地区肿瘤死亡的主要原因。这种食管癌和贲门癌高发区并存的情况还见于世界其他食管癌高发区。本实验室自95年对该地区人群普查、随访发现:同一个体同时发生食管鳞癌和贲门腺癌的患者并非罕见我们称之为食管/贲门双源癌(Primary Concurrent Cancers of the Esophagus and Gastric Cardia from the Same Patient,CC)(约为2.5%)。这两种组织学类型不同的肿瘤并存的现象提示,二者可能是一种相关性疾病,可能具有相似的致病危险因素和发病机理。食管贲门双源癌发生在同一个体,故认为这两种肿瘤的遗传背景,内外环境因素有很大的相似性,系统分析这一独特病例的分子变化和规律,将对阐明食管贲门癌变机理,食管/贲门癌高易感性的分子机制,肿瘤多中心起源理论,特别是回答该地区食管鳞癌和贲门腺癌并存高发是否具有相似的癌变分子基础及致癌危险因素等方面均有重要理论意义。目前国内外有关食管和贲门双源癌的研究报道甚少,食管/贲门癌变的发生机制尚不十分清楚。更多还原

【Abstract】 Esophageal squamous cell carcinoma (SCC) and gastric cardic adenocarcinoma (GCA) are the most common malignant diseases in Henan province, and remain the leading cause of cancer related deaths in these areas. SCC seems to occur together with GCA, which could be observed in other counties over the world. It is noteworthy that Primary Concunent Cancers of the Esophagus and Gastric Cardia from the Same Patient (CC), is not uncommon in this area (2.5%), which indicates that there may be similar risk factors and mechanism involved in SCC and GCA. The prevalence and mechanisms for CC is still not clear. To further characterize the changes of CC patients may shed light on the mechanisms and etiological clues for this special disease.Recent studies indicate that carcinogenesis of SCC/GCA is a multi-stepprogressive process involved by multiple genetic changes (accumulation or overlap). The P53-Rb pathway, including P53, Rb, P16, Bcl-2, BAX, P14, P21wafl, has been demonstrated the frequent molecular event involved in SCC by us and other laboratories. P53 mutation and Rb LOH may play an important role to drive the mild esophageal precancerous lesion to cancer by striking the abnormal esophageal epithelial cell proliferation. The derangement of cellular proliferation makes cellular clone faster and provoke the formation of cancer. In addition, our recent studies have showed that accumulation of P53 protein and P53 gene mutation occur in the very early stage of esophageal carcinogenesis.To understand the molecular mechanisms of SCC/GCA carcinogenesis and to identify the biomarkers for early detection of high-risk subjects for SCC and GCA, the present study was undertaken to characterize the alternations of Rb, P21wafl, Bcl-2 > BAX^ P53 and PCNA on the CC patients from the high incidence area in Henan.1.2.1 Materials and Methods:Thirty cases with concurrent cancers of SCC and GCA enrolled in this study were from Linzhou City Hospital, Yaocun Esophageal Cancer Hospital and Luoyang Third People’s Hospital, the high-incidence areas for SCC. Of the patients, 22 were males and 8 females, with a mean age of 62 ± 7 years in male and 63 ± 7 years in female . All the patients were not treated by either chemotherapy or radiotherapy before operation. All the resected tissues were fixed with alcohol, paraffin embedded and partial serially sectioned for histopathological diagnosis, histochemical staining, and immunostaining. The diagnosis of CC was based on the criteria: 1) the tumors must be clearly separated on histological pattern; 2) the tumors must be malignancy; and3) metastasis must be excluded. Immunohistochemistry (ABC) method was applied to determine the expression of Rb, P21WAF1, Bcl-2, BAX, P53 and PCNA. The x2Test, Spearman Correlation Test, Fisher’s Exact Test and Kappa Test were applied for thestatistics (p<0.05 was considered significant). 1.2.2 Results:Clinicopathological analysis:Among the 30 CC patients, the sex ratio was 2.33:1. 21 patients were over 50 years old (70%). Gross observation showed that both SCC and GCA occured independently, with distance of 3 to 7 cm, and mucosa between the two tumors showed normal by naked eyes. Histopathologically, all the 30 cases were conformed with both primary SCC and GCA. TNM classification: in SCC, there were 17 cases with stage II (57%) , 10 cases with stage I (33%), and 3 cases with stage III (10%); in GCA, there were 15 cases with stage II (50%) , 10 cases with stage I (33%), 4 cases with stage III and IV (13%) and 1 case with stage 0 (3%) . The interesting observation was that the mixture of SCC and GCA tissues occurred occasionally in the same field under microscope.Immunohistochemical staining (IHC)In CC patients, the positive immunohistochemical staining for Rb, P21wafl, Bcl-2, BAX, P53 and PCNA both in SCC and GCA was observed with different degrees. In SCC, the overexpression rates of BAX was the highest with 83% (25/30), followed by Bcl-2. P53 and PCNA with 77% (23/30) ,67% (20/30) , and 73% (22/30), respectively. The expression rates of Rb and P21wafl were 47% (14/30), 20% (6/30) . In GCA, the overexpression rates of Bcl-2, BAX, P53 and PCNA were similar , with 63% (19/30) , 67% (20/30) , 70% (21/30) , and 77% (23/30) , respectively; while that of Rb> P21wafl were low , with 40% (12/30), 30% (9/30), respectively. "Diffuse" immunostaining pattern was frequently observed in Bcl-2, BAX, P53 and PCNA, and "Scatter" immunostaining pattern was frequentlyobserved in Rb and P21wafl. High coincidence rates for Rb, P21wafl, Bcl-2, BAX, P53 and PCNA positive staining was observed in SCC and GCA from the same patients. PCNA was observed with the highest coincidence rate (97%), followed by Rb, P21wafl, Bcl-2 (87%, 80%, 80%) and BAX and P53 (67% and 60%).1.2.3 Conclusion:Bcl-2, BAX, P53 and PCNA were the most frequent biomarkers in the carcinogenesis of SCC and GCA.The high coincident alterations for Rb, P21wafl, Bcl-2, BAX, P53 and PCNA in SCC and GCA from the same patient suggest the possibility of similar molecular basis, and etiological clue for similar risk factors involved in SCC and GCA.更多还原