Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA.
Mod Pathol. 2011 Sep;24(9):1248-53. doi: 10.1038/modpathol.2011.85. Epub 2011 May 6.
Immunohistochemical staining for p53 is used as a surrogate for mutational analysis in the diagnostic workup of carcinomas of multiple sites including ovarian cancers. Strong and diffuse immunoexpression of p53 is generally interpreted as likely indicating a TP53 gene mutation. The immunoprofile that correlates with wild-type TP53, however, is not as clear. In particular, the significance of completely negative immunostaining is controversial. The aim of this study was to clarify the relationship of the immunohistochemical expression of p53 with the mutational status of the TP53 gene in ovarian cancer. A total of 57 ovarian carcinomas (43 high-grade serous ovarian/peritoneal carcinomas, 2 malignant mesodermal mixed tumors (carcinosarcomas), 2 low-grade serous carcinomas, 4 clear cell carcinomas, 1 well-differentiated endometrioid carcinoma, and 5 carcinomas with mixed epithelial differentiation) were analyzed for TP53 mutations by nucleotide sequencing (exons 4-9), and subjected to immunohistochemical analysis of p53 expression. Thirty six tumors contained functional mutations and 13 had wild type TP53. Five tumors were found to harbor known TP53 polymorphism and changes in the intron region were detected in three. Tumors with wild-type TP53 displayed a wide range of immunolabeling patterns, with the most common pattern showing ≤10% of positive cells in 6 cases (46%). Mutant TP53 was associated with 60-100% positive cells in 23 cases (64% of cases). This pattern of staining was also seen in three cases with wild-type TP53. Tumors that were completely negative (0% cells staining) had a mutation of TP53 in 65% of cases and wild-type TP53 in 11%. Combining two immunohistochemical labeling patterns associated with TP53 mutations (0% and 60-100% positive cells), correctly identified a mutation in 94% of cases (P<0.001). Immunohistochemical analysis can be used as a robust method for inferring the presence of a TP53 mutation in ovarian carcinomas. In addition to a strong and diffuse pattern of p53 expression (in greater than 60% of cells), complete absence of p53 immunoexpression is commonly associated with a TP53 mutation. Accordingly, this latter pattern, unlike low-level expression (10-50% cells), should not be construed as indicative of wild-type TP53.
免疫组织化学染色 p53 被用作多种部位包括卵巢癌的癌诊断工作中突变分析的替代物。p53 的强弥漫性免疫表达通常被解释为可能表明 TP53 基因突变。然而，与野生型 TP53 相关的免疫表型并不明确。特别是，完全阴性免疫染色的意义存在争议。本研究旨在阐明卵巢癌中 p53 的免疫组织化学表达与 TP53 基因突变状态的关系。共分析了 57 例卵巢癌（43 例高级别浆液性卵巢/腹膜癌、2 例恶性中胚叶混合瘤（癌肉瘤）、2 例低级别浆液性癌、4 例透明细胞癌、1 例高分化子宫内膜样癌和 5 例具有混合上皮分化的癌）的 TP53 基因突变，采用核苷酸测序（外显子 4-9）进行分析，并进行 p53 表达的免疫组织化学分析。36 个肿瘤含有功能突变，13 个肿瘤有野生型 TP53。发现 5 个肿瘤携带已知的 TP53 多态性，3 个肿瘤检测到内含子区域的变化。野生型 TP53 的肿瘤显示出广泛的免疫标记模式，其中 6 例（46%）最常见的模式是≤10%的阳性细胞。突变型 TP53 与 23 例中 60-100%的阳性细胞相关（64%的病例）。在 3 例野生型 TP53 中也观察到这种染色模式。完全阴性（0%细胞染色）的肿瘤中有 65%的病例存在 TP53 突变，11%的病例存在野生型 TP53。结合与 TP53 突变相关的两种免疫组织化学标记模式（0%和 60-100%的阳性细胞），正确识别了 94%的病例（P<0.001）。免疫组织化学分析可作为推断卵巢癌中 TP53 突变存在的一种强大方法。除了强弥漫性的 p53 表达模式（大于 60%的细胞）外，p53 免疫表达完全缺失通常与 TP53 突变相关。因此，与低水平表达（10-50%的细胞）不同，这种后一种模式不应被解释为野生型 TP53。
