Lazăr Daniela, Tăban Sorina, Sporea I, Dema Alis, Cornianu Mărioara, Lazăr Elena, Goldiş A, Raţiu Iulia, Vernic C
Department of Gastroenterology and Hepatology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania.
Rom J Morphol Embryol. 2010;51(2):249-57.
P53-tumor suppressor gene has an essential role in controlling cell cycle and initiating carcinogenesis. In the case of gastric cancer, the role of p53-protein accumulation as prognostic factor is controversy. Various results are due to the different methods of study regarding patients' selection, immunohistochemical techniques used and the quantifying systems for immunoreactions.
Assessment of p53-immunohistochemical expression in 61 patients with gastric carcinomas and the correlation with clinicopathological factors (gender, age, location, macroscopic, and histological type, degree of tumor differentiation and TNM-stage) and patients' survival.
From the total number of 265 patients (186 males and 79 females) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of five years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). We used the monoclonal antibody DO7 that detects the wild and mutant form of p53-protein, by EnVision technique and DAB-visualization. We considered positive reaction only in the presence of brown staining of the nuclei.
P53-immunoreactions were positive in 25 gastric cancers (41%). We obtained positive stainings in 41.9% cases in men and 38.9% women. We found positive p53-immunoreactions in all the carcinomas developed in the upper third of the stomach (100%), in 53.3% of the corporeal tumors, 50% of the pangastric tumors; according to Lauren's classification, we noticed a significantly increased immunoreaction of p53 in the intestinal-type carcinomas. Among histological types, papillary, mucinous, anaplastic and tubular adenocarcinomas presented a relatively increased percentage of p53-positive immunoreactions. P53-positive stainings are more frequently encountered in moderate/poor differentiated carcinomas and those associated with lymphovascular invasion; according to pT- and pN-stage, we remarked a significantly increase of the number of p53-positive cases (p=0.02291 and p=0.038264). Five-year survival rate for patients with p53-positive carcinomas was significantly lower in comparison to the patients p53-negative (8% vs. 22.2%, p=0.0326).
Immunohistochemical evaluation of p53-protein represents in our study an important prognostic factor, allowing the selection of a group of patients with an aggressive therapeutic indication, such as extensive lymphadenectomy and adjuvant chemotherapy.
p53肿瘤抑制基因在控制细胞周期和启动癌变过程中起着至关重要的作用。在胃癌病例中,p53蛋白积累作为预后因素的作用存在争议。各种结果归因于关于患者选择、所使用的免疫组织化学技术以及免疫反应定量系统的不同研究方法。
评估61例胃癌患者中p53免疫组织化学表达情况,并探讨其与临床病理因素(性别、年龄、部位、大体类型、组织学类型、肿瘤分化程度和TNM分期)及患者生存率的相关性。
从1998 - 2002年期间诊断为胃癌的265例患者(186例男性和79例女性)中,选取61例接受手术的患者。对该组患者进行了为期五年的关于胃癌进展和侵袭性的前瞻性研究。生存时间从手术干预月份计算至死亡月份或生存确认月份,生存率以观察期结束时(以年和月计)的存活百分比表示。我们使用单克隆抗体DO7,通过EnVision技术和DAB显色法检测p53蛋白的野生型和突变型。仅在细胞核出现棕色染色时才视为阳性反应。
25例胃癌(41%)的p53免疫反应呈阳性。男性患者阳性染色率为41.9%,女性为38.9%。我们发现胃上部三分之一处发生的所有癌(100%)、胃体部肿瘤的53.3%、全胃癌的50%中p53免疫反应呈阳性;根据劳伦分类法,我们注意到肠型癌中p53的免疫反应显著增加。在组织学类型中,乳头状、黏液性、间变性和管状腺癌的p53阳性免疫反应百分比相对增加。p53阳性染色在中/低分化癌以及伴有淋巴管侵犯的癌中更常见;根据pT和pN分期,我们发现p53阳性病例数显著增加(p = 0.02291和p = 0.038264)。p53阳性癌患者的五年生存率明显低于p53阴性患者(8%对22.2%,p = 0.0326)。
在我们的研究中,p53蛋白的免疫组织化学评估是一个重要的预后因素,有助于选择一组具有积极治疗指征的患者,如广泛淋巴结清扫和辅助化疗。