Jeffers M D, Farquharson M A, Richmond J A, McNicol A M
University Department of Pathology, Glasgow Royal Infirmary University NHS Trust, Scotland, UK.
J Pathol. 1995 Sep;177(1):65-70. doi: 10.1002/path.1711770111.
Mutation and overexpression of p53 have been described in uterine malignant mixed Müllerian tumours and in endometrial adenocarcinoma, where it has been associated with a poor prognosis. This study examines p53 expression and mutation of the p53 gene in benign and malignant smooth muscle tumours of the uterine corpus. p53 expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded tissue from 23 leiomyosarcomas, 10 tumours of uncertain malignant potential (TUMPs), and 18 leiomyomas. Single-stranded conformational polymorphism, (SSCP) analysis of exons 5-8 of the p53 gene was performed on 13 leiomyosarcomas, nine TUMPs, and eight leiomyomas. With microwave antigen retrieval, p53 immunoreactivity was seen in 13/23 microwave treatment, staining was abolished in three leiomyosarcomas, all immunoreactive TUMPs, and the single positive leiomyoma. SSCP analysis revealed mutation in three leiomyosarcomas. There was one mutation in exon 5 in a case with positive immunohistochemistry. Two cases with negative staining showed mutation, one in exon 7 and one in exon 8. Mutation was present in exon 7 in 4/9 and in exon 6 in 1/9 TUMPs. All of these cases showed positive immunohistochemistry. There was no significant difference in outcome between cases with and without positive immunohistochemistry. p53 expression is seen in a significant proportion of uterine leiomyosarcomas. Microwave antigen retrieval increases the proportion of positive cases and also results in positive staining in TUMPs. Mutation of the p53 gene occurs in only a minority of leiomyosarcomas and in a significant proportion of TUMPs. Positive immunohistochemistry does not, however, correlate with the presence of mutation and other factors may be responsible for p53 detection in many cases.
p53的突变和过表达已在子宫恶性混合性苗勒管肿瘤和子宫内膜腺癌中被描述,在这些肿瘤中它与预后不良相关。本研究检测子宫体良性和恶性平滑肌肿瘤中p53的表达及p53基因的突变情况。采用免疫组织化学方法对23例平滑肌肉瘤、10例恶性潜能不确定肿瘤(TUMPs)和18例平滑肌瘤的福尔马林固定、石蜡包埋组织进行p53表达评估。对13例平滑肌肉瘤、9例TUMPs和8例平滑肌瘤进行p53基因第5至8外显子的单链构象多态性(SSCP)分析。经微波抗原修复后,23例中有13例平滑肌肉瘤出现p53免疫反应性,3例平滑肌肉瘤、所有免疫反应性TUMPs及1例阳性平滑肌瘤的染色被消除。SSCP分析显示3例平滑肌肉瘤存在突变。1例免疫组织化学阳性病例的第5外显子有1个突变。2例染色阴性病例显示有突变,1例在第7外显子,1例在第8外显子。9例TUMPs中有4例第7外显子存在突变,1例第6外显子存在突变。所有这些病例免疫组织化学均呈阳性。免疫组织化学阳性和阴性病例的预后无显著差异。相当一部分子宫平滑肌肉瘤可见p53表达。微波抗原修复增加了阳性病例的比例,也使TUMPs出现阳性染色。p53基因突变仅发生在少数平滑肌肉瘤和相当一部分TUMPs中。然而,免疫组织化学阳性与突变的存在无关,在许多情况下其他因素可能导致p53的检测呈阳性。