罕见的呼吸道乳头状瘤病的恶性转化与人类乳头状瘤病毒6型感染和p53过度表达相关

目前认为，呼吸道乳头状瘤病（RRP）是由于6型或11型人类乳头状瘤病毒（HPV）感染导致上呼吸道反复出现弥漫性乳头状瘤的一种慢性疾病。虽然RRP是一种顽固性疾病，但其极少恶变，且具体的机制目前尚未完全清楚。最近，日本研究人员详细介绍了1例经历超过130次手术并最终恶化为鳞状细胞癌的HPV6阳性RRP患者的临床过程。

胃癌p53、rasp21和nm23/DNPK的免疫组化研究

目的探讨p53、rasp21和nm23/DNPK的表达在胃癌的发生、浸润和转移中的作用。方法应用免疫组化SP法,检测82例胃癌及其癌旁组织中p53、rasp21和nm23/DNPK表达。结果胃癌中p53、rasp21和nm23/DNPK表达分别为68.3%、61.0%、56.1%;癌旁组织中rasp21、nm23/DNPK分别为17.1%、48.8%,p53无阳性表达;rasp21过度表达与浸润深度有关(P<0.05),p53过度表达,nm23/DNPK低表达与淋巴结转移有关(P<0.05)。p53的表达与rasp21的表达之间有显著相关(P<0.05)。结论p53突变和ras基因的激活与胃癌的发生发展有关,两者之间具有协同作用。nm23/DNPK低表达与淋巴结转移有关。

Correlation of p53 over-expression and alteration in p53 gene detected by polymerase chain reaction-single strand conformation polymorphism in adenocarcinoma of gastric cancer patients from India

AIM： To study the alterations in p53 gene among Indian gastric cancer patients and to correlate them with the various clinicopathological parameters. METHODS： A total of 103 gastric cancer patients were included in this study. The p53 alterations were studied by both immunohistochemical method as well as polymerase chain reaction （PCR）-single strand conformation polymorphism （SSCP） analysis. We only studied four （exon 5, 6, 7, and 8） of the 11 ,p53 exons. The alterations in p53 were also correlated with respect to various clinicopathological parameters. RESULTS： Among 103 cases, p53 over-expression and alteration were detected in 37 （35.92%） and 19 （18.44%） cases, respectively. Most of the ,p53 alterations were found at exon 5 （31.54%）, followed by exon 6 （26.31%）, exon 7 （21.04%） and exon 8 （21.04%）. A significant correlation of p53 overexpression was found with p53 alteration （P = 0.000）. Concordance between ,p53 alteration （as detected by SSCP） and over-expression [as detected by immunohistochemistry （IHC）] was found in 75% cases. We found that IHC-positive/SSCP-negative cases accounted for 21% of cases and IHC-negative/SSCP- positive cases accounted for remaining 4% cases. CONCLUSION： Our results show that p53 gene mutations are significantly correlated with p53 protein over-expression, with 75% concordance in over-expression and alteration in the p53 gene, but 25% disconcordance also cautions against the assumption that p53 over-expression is always associated with a gene mutation. There may be other mechanisms responsible for stabilization and accumulation of p53 protein with no evidence of gene mutation that reflect an accumulation of a non-mutated protein, or a false negative SSCP result.

脆性组氨酸三联体基因和p53在宫颈浸润癌和癌前病变组织中的表达及意义

目的探讨脆性组氨酸三联体基因(FHIT)表达缺失或下降和p53的过度表达在宫颈癌发生发展中的意义。方法2001年1月至2003年1月温州医学院附属第一医院采用免疫组化SP法检测52例宫颈上皮内瘤样病变(CIN)和69例宫颈浸润癌组织中的FHIT基因和p53的表达,并以18例慢性宫颈炎组织为对照。结果FHIT在慢性宫颈炎组织中呈100%表达。在宫颈CINⅠ、Ⅱ、Ⅲ的下降或缺失率分别占9.1%、29.4%和41.7%。在宫颈浸润癌中的下降或缺失率占66.7%,其中鳞癌低表达率为75.4%,较腺癌的25.0%差异有显著性意义(P<0.01),临床Ⅰ、Ⅱ期和Ⅲ或Ⅳ期的缺失率分别为60.7%、65.2%和77.8%,组织学分级G1、G2和G3的缺失率分别为47.4%、64.3%和86.4%,临床Ⅰ、Ⅱ期与Ⅲ或Ⅳ期比较,组织学分级G1及G2与G3比较差异均有显著性意义(P<0.05)。p53在慢性宫颈炎组织无表达,在宫颈浸润癌中呈56.5%阳性表达,且随着临床期别的增高、细胞分化的降低以及淋巴转移的出现进一步上升。p53阳性的宫颈癌中FHIT缺失为74.4%,而p53阴性的FHIT缺失占56.7%,两者比较差异无显著性意义(P>0.05)。结论FHIT基因下降或缺失与p53过度表达是宫颈癌的频发事件,测定宫颈CIN中FHIT可作为宫颈癌的高危人群筛选指标,FHIT与p53检测还可作为宫颈癌的预后指标。