Norfadzilah M Y, Pailoor Jayalakshmi, Retneswari M, Chinna K, Noor Laili M M
Department of Pathology, University of Malaya, Kuala Lumpur Malaysia.
Malays J Pathol. 2011 Dec;33(2):89-94.
Patients with pancreatic adenocarcinoma are known to have a high mortality rate. The 5-year survival rate still remains low even now compared to that of the 1960's despite new advances in management including surgery, chemotherapy, pathological classification and molecular diagnostic technologies. Precursors to invasive pancreatic adenocarcinoma have been identified in the last ten years that include mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia. p53 protein accumulation in the nuclei is a common molecular event in most human neoplasms. Our objective is to investigate p53 expression in pancreatic adenocarcinoma and precursor lesions and their significance. The selected study material encompassed 31 invasive ductal adenocarcinoma, 15 mucinous cystic neoplasm and papillary mucinous neoplasm, and 27 cases of pancreatic intraepithelial neoplasia including grade 1, 2 and 3. Immunoscore was given for each case based on intensity of staining and percentage of cells positive and compared between precursor lesions and invasive adenocarcinoma. A score of 50 and above was considered significant. The results showed that p53 expression increased progressively and significantly with the grade of pancreatic intraepithelial neoplasia and adenocarcinoma (p-value < 0.001). These findings support the concept of multistep carcinogenesis in pancreatic adenocarcinoma and suggest that p53 inactivation occurs in the progression of precursors to pancreatic adenocarcinoma.
已知胰腺腺癌患者的死亡率很高。尽管在包括手术、化疗、病理分类和分子诊断技术在内的治疗方面取得了新进展，但与20世纪60年代相比，即使在现在，5年生存率仍然很低。在过去十年中已经确定了浸润性胰腺腺癌的前驱病变，包括黏液性囊性肿瘤、导管内乳头状黏液性肿瘤和胰腺上皮内瘤变。细胞核中p53蛋白的积累是大多数人类肿瘤中常见的分子事件。我们的目的是研究p53在胰腺腺癌及其前驱病变中的表达及其意义。所选研究材料包括31例浸润性导管腺癌、15例黏液性囊性肿瘤和乳头状黏液性肿瘤，以及27例胰腺上皮内瘤变病例，包括1级、2级和3级。根据染色强度和阳性细胞百分比对每个病例进行免疫评分，并在前驱病变和浸润性腺癌之间进行比较。50分及以上被认为具有显著性。结果显示，p53表达随着胰腺上皮内瘤变和腺癌的分级而逐渐显著增加（p值<0.001）。这些发现支持胰腺腺癌多步骤致癌的概念，并表明p53失活发生在胰腺腺癌前驱病变的进展过程中。
