p53蛋白表达和基因突变在所谓肺硬化性血管瘤组织中的意义

背景与目的所谓肺硬化性血管瘤（so-called pulmonary sclerosing hemangioma，PSH）是一种至今不能肯定其来源及性质的少见肺肿瘤。虽然目前普遍认为PSH是一种良性肿瘤，但却发现有少数PSH可发生浸润和转移。p53蛋白表达和基因突变是反映肿瘤生物学行为的有用指标。本研究的目的是检测PSH组织中p53基因突变及p53蛋白的表达情况及其意义。方法应用免疫组化S-P法、激光捕获显微切割（laser capture microdissection，LCM）技术、单链构象多态性（single-stranded conformation polymorphism，SSCP）及DNA测序分析方法（5～8外显子）检测19例PSH中多角形细胞和表面立方细胞的p53蛋白表达和基因突变情况。结果19例PSH组织中p53蛋白阳性表达率为21．1％（4／19），SSCP及测序分析检测p53基因突变率分别为26．3％（5／19）和42．1％（8／19）。p53蛋白阳性表达的4例PSH组织，测序分析显示3例标本有突变发生，2例为错义突变，1例同时发生错义突变和移码突变；而p53蛋白阴性表达的15例PSH组织中，5例标本经测序证实亦发生了突变，4例为移码突变，1例为错义突变。在有突变的8例PSH组织中，单一多角形细胞突变5例，单一立方细胞突变2例，多角形细胞和立方细胞同时突变1例。结论PSH组织p53蛋白阳性表达并不能完全反映p53基因突变的真实情况；p53基因突变或蛋白表达异常均可发生在PSH组织中的两种不同的细胞内；p53基因的高突变率提示PSH可能具有潜在的恶性生物学行为。

Significance of p53 protein expression and p53 gene mutation in so-called pulmonary sclerosing hemangioma

Background and objective So-called pulmonary sclerosing hemangioma (PSH) is an uncommon tumor of the lung and its histogenesis and origin are uncertain to date. A general consensus appears to have been reached that PSH is a benign neoplasm, but a few PSHs are found to invade and metastasize. The expression of p53 protein and mutation of p53 gene are significant parameters which can reflect biological behavior of tumor cells. The aim of this study is to investigate the p53 protein expression and p53 gene mutation in PSH, and explore their significance. Methods The expression of p53 protein and mutation of p53 gene were examined in polygonal cells and cuboidal cells of PSH by immunohistochemical method, laser capture microdissection (LCM), single-stranded conformation polymorphism (SSCP) and DNA sequencing. Results The positive rate of p53 protein was 21.1% (4/19) and the mutation rate of p53 gene was 26.3% (5/19) by SSCP and 42.1% (8/19) by DNA sequencing respectively. In 4 cases of immunopositive PSH tissues, 2 were missense mutations, and 1 was both missense and frameshift mutation. Out of 15 cases of immunonegative PSH tissues, 4 were frameshift mutations and 1 was missense mutation. Of 8 PSH tissues with p53 gene mutation, 5 were identified in only polygonal cells, and 2 in only cuboidal cells and 1 in both polygonal and cuboidal cells. Conclusion The expression of p53 protein may not be indicative of p53 gene mutation in PSH. The alteration of p53 gene and the expression of p53 protein are identified in both polygonal and cuboidal cells. The high mutation rate of p53 gene may indicate that PSH has potentially malignant biological behavior.