Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Pathology. 2023 Oct;55(6):785-791. doi: 10.1016/j.pathol.2023.04.008. Epub 2023 Jul 11.
In gynecological neoplasms, immunohistochemical (IHC) expression of p53 is generally an accurate predictor of TP53 mutation status if correctly interpreted by the pathologist. However, the literature concerning cut-offs, frequency and prognostic significance of p53 staining in ovarian mucinous tumours is limited and heterogeneous. We performed an analysis of 123 primary ovarian mucinous tumours including mucinous borderline tumours (MBT), mucinous carcinomas (MC), and tumours with equivocal features between MBT and MC. We assessed p53 expression for the three recognised patterns of aberrant staining in ovarian carcinoma [overexpression ('all'), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tumours (strong nuclear p53 staining in ≥12 consecutive tumour cells) and correlated the results with next generation sequencing (NGS) in all qualitatively sufficient cases (92/123). Aberrant p53 expression was present in 25/75 (33.3%) MBT, 23/33 (69.7%) MC (75% of MC with expansile invasion and 61.5% with infiltrative invasion), and 10/15 (66.7%) tumours equivocal between MBT and MC. Regarding the 92 tumours with paired IHC and mutation results, 86 showed concordant results and six cases were discordant. Three discordant MBT cases showed aberrant expression but were TP53 wild-type on sequencing. Three cases had normal p53 expression but contained a TP53 mutation. Overall, IHC predicted the TP53 mutation status with high sensitivity (94.1%) and specificity (92.7%). The accuracy of IHC was 93.5% with a positive predictive value of 94.1% and a negative predictive value of 92.7%. When comparing MC cases with wild-type TP53 versus those with TP53 mutation, there were no significant differences concerning disease-free survival, local recurrence-free survival, or metastases-free survival (p>0.05). In the MBT subgroup, there were no events for survival analyses. In conclusion, using an independent large sample set of ovarian mucinous tumours, the results of our study confirm that the suggested refined cut-off of strong nuclear p53 staining in ≥12 consecutive tumour cells reflect high accuracy, sensitivity and specificity for an underlying TP53 mutation but the TP53 mutation status has no prognostic significance in either MC or MBT.
在妇科肿瘤中，如果病理学家正确解读，免疫组织化学（IHC）表达的 p53 通常是 TP53 突变状态的准确预测指标。然而，关于卵巢黏液性肿瘤中 p53 染色的截断值、频率和预后意义的文献是有限的和异质的。我们对 123 例原发性卵巢黏液性肿瘤进行了分析，包括黏液性交界性肿瘤（MBT）、黏液性癌（MC）和 MBT 与 MC 之间特征不确定的肿瘤。我们评估了 p53 表达的三种公认的卵巢癌异常染色模式[过表达（“全部”）、缺失和细胞质]，但使用了最近提出的卵巢黏液性肿瘤中异常过表达的截断值（≥12 个连续肿瘤细胞中的强核 p53 染色），并将结果与所有定性充分的病例（92/123）的下一代测序（NGS）相关联。在 75 例 MBT 中，25 例（33.3%）存在异常 p53 表达，在 33 例 MC 中，23 例（69.7%）存在异常 p53 表达（75%的 MC 具有膨胀性浸润，61.5%的 MC 具有浸润性浸润），在 15 例 MBT 和 MC 之间特征不确定的肿瘤中，10 例（66.7%）存在异常 p53 表达。关于 92 例具有配对 IHC 和突变结果的肿瘤，86 例显示出一致的结果，6 例显示出不一致的结果。3 例不一致的 MBT 病例表现出异常表达，但测序显示 TP53 野生型。3 例具有正常的 p53 表达，但含有 TP53 突变。总的来说，IHC 对 TP53 突变状态具有较高的敏感性（94.1%）和特异性（92.7%）。IHC 的准确性为 93.5%，阳性预测值为 94.1%，阴性预测值为 92.7%。当比较 TP53 野生型 MC 病例与 TP53 突变型 MC 病例时，在无疾病生存、局部无复发生存或无转移生存方面没有显著差异（p>0.05）。在 MBT 亚组中，无生存分析事件。总之，使用卵巢黏液性肿瘤的独立大样本集，本研究的结果证实，建议的强核 p53 染色在≥12 个连续肿瘤细胞中的截断值反映了 TP53 突变的高准确性、敏感性和特异性，但 TP53 突变状态在 MC 或 MBT 中均无预后意义。
