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Abstract：
OBJECTIVE: The importance of a TP53 mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with TP53 mutations in breast cancers from 64 patients.
METHODS: TP53 mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC).
RESULTS: Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A TP53 mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a TP53 mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (p < 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense TP53 mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (p < 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (p < 0.05).
CONCLUSIONS: These findings suggest that p53 IHC can be a potential surrogate for TP53 mutations in BC. Different p53 expression patterns may correlate with specific TP53 genetic mutations in BC.
METHODS: TP53 mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC).
RESULTS: Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A TP53 mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a TP53 mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (p < 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense TP53 mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (p < 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (p < 0.05).
CONCLUSIONS: These findings suggest that p53 IHC can be a potential surrogate for TP53 mutations in BC. Different p53 expression patterns may correlate with specific TP53 genetic mutations in BC.
摘要：
目的：TP53突变的重要性已在几种肿瘤类型中得到证实，包括乳腺癌（BC）。然而,p53蛋白表达作为基因突变预测因子的准确性在BC中尚未得到很好的研究。因此,我们评估了64例乳腺癌患者中与TP53突变相关的p53蛋白表达.
方法：使用下一代测序（NGS）检查TP53突变。使用免疫组织化学(IHC)检查p53蛋白表达。
结果：在64个BC中，55%表现出异常表达模式，包括27%的过表达，22%null,6%模棱两可，45%具有野生型模式。TP53突变存在于53％（34/64）的肿瘤中，包括30％（19/64）显示错义突变，11%（7/64）具有移码突变，11%（7/64）具有无义突变，3％（1/64）具有剪接位点突变。p53蛋白的异常表达在34个携带TP53突变的肿瘤中有33个（97％）存在；相反，30例肿瘤中有28例(93%)存在野生型模式,但没有可检测到的突变(p<0.0001).大多数具有p53IHC过表达模式的BC(15/17,88%)含有错义TP53突变;而大多数具有无效模式的BC(12/14,86%)含有截短突变(p<0.0001)。当与显示过表达的那些相比时,具有无效模式的BC与高诺丁汉组织学分级和三阴性表型相关(p<0.05)。
结论：这些研究结果表明p53IHC可能是BC中TP53突变的潜在替代。不同的p53表达模式可能与BC中特定的TP53基因突变相关。
方法：使用下一代测序（NGS）检查TP53突变。使用免疫组织化学(IHC)检查p53蛋白表达。
结果：在64个BC中，55%表现出异常表达模式，包括27%的过表达，22%null,6%模棱两可，45%具有野生型模式。TP53突变存在于53％（34/64）的肿瘤中，包括30％（19/64）显示错义突变，11%（7/64）具有移码突变，11%（7/64）具有无义突变，3％（1/64）具有剪接位点突变。p53蛋白的异常表达在34个携带TP53突变的肿瘤中有33个（97％）存在；相反，30例肿瘤中有28例(93%)存在野生型模式,但没有可检测到的突变(p<0.0001).大多数具有p53IHC过表达模式的BC(15/17,88%)含有错义TP53突变;而大多数具有无效模式的BC(12/14,86%)含有截短突变(p<0.0001)。当与显示过表达的那些相比时,具有无效模式的BC与高诺丁汉组织学分级和三阴性表型相关(p<0.05)。
结论：这些研究结果表明p53IHC可能是BC中TP53突变的潜在替代。不同的p53表达模式可能与BC中特定的TP53基因突变相关。
