High-grade serous carcinoma with discordant p53 signature: report of a case with new insight regarding high-grade serous carcinogenesis.
High-grade serous carcinoma with discordant p53 signature: report of a case with new insight regarding high-grade serous carcinogenesis.
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DOI：
10.1186/s13000-018-0702-3
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发表时间：
2018-04-27
影响因子：
2.6
通讯作者：
Hara A
中科院分区：
文献类型：
--
作者：
Hatano Y;Fukuda S;Makino H;Tomita H;Morishige KI;Hara A
尽管在输卵管中经常发现P53信号，即弥漫表达P53的良性上皮细胞，但这种病变在高级别浆液性癌(HGSC)患者中的临床和病理意义仍不清楚。一名56岁女性因腹胀被转诊至妇科医生。由于放射学和血清学检查显示她的疾病是由于晚期卵巢癌(FIGO期IVB)，她接受了新辅助化疗，临床评价化疗反应为部分反应。她接受了全子宫切除，双侧输卵管卵巢切除，大网膜切除，盆腔内和腹主动脉旁淋巴清扫。组织学上，癌细胞呈高度异型性，扩散至双侧卵巢、大网膜、子宫浆膜和左侧输卵管。癌细胞完全不表达P53但过表达p16，而部分良性输卵管上皮细胞过表达P53但缺乏p16表达。直接测序结果显示，卵巢癌组织中存在TP53基因第8外显子1个碱基的缺失。最后，对P53信号不一致的HGSC进行组织学诊断。有趣的是，γ-H_2AX的核表达不仅在p53异常表达的病变中观察到，而且在无P53过表达的良性输卵管上皮中也可观察到。在组织学确诊后，她接受了辅助化疗，5个半月来一直处于无病状态，没有发现任何肿瘤。最近的证据表明，P53信号可能是P53过表达型HGSC的先兆。由于其他P53免疫表型HGSC的前体尚未被提出，我们推测无P53过表达的γ-H_2AX表达细胞可能是被命名为“γ-H_2AX反应灶”的突变型输卵管细胞的有效候选者。
Although p53 signature, benign-appearing epithelial cells with p53 diffuse expression, is frequently found in the fallopian tubes, the clinical and pathological significance of this lesion in the case of high-grade serous carcinoma (HGSC) patients still remains unclear. A 56-year-old woman was referred to the gynecologist on account of abdominal distention. Since radiological and serological workup suggested that her illness was due to advanced ovarian cancer (FIGO Stage IVB), she received neoadjuvant chemotherapy, and the clinical evaluation of the chemotherapeutic response was a partial response. She underwent total hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and intra-pelvic and para-aortic lymphadenectomy. Histologically, the cancer cells showed high-grade nuclear atypia and spread into the bilateral ovaries, omentum, uterine serosa, and left fallopian tube. The cancer cells showed complete absence of p53 but overexpressed p16, whereas some of benign-appearing tubal epithelial cells overexpressed p53 but lacked p16 expression. The results of direct sequence analysis revealed that the ovarian cancer contains a 1 bp deletion in exon 8 of TP53. Finally, the histological diagnosis of HGSC with discordant p53 signature was made. Interestingly, nuclear expression of γ-H2AX, a well-known marker of DNA damage, was not only observed in both p53 aberrantly-expressing lesions but also the benign-appearing tubal epithelium without p53 overexpression. After the histological confirmation, she received adjuvant chemotherapy and has been in disease-free condition without any detectable tumor for 5 months. Recent evidence suggests that p53 signature is the putative precursor of p53 overexpression-type HGSC. Because the putative precursors of the other p53 immunophenotypical HGSC are not proposed, we presume γ-H2AX-expressing cells without p53 overexpression may be a potent candidate of null-type TP53-mutated tubal cells, which are named “γ-H2AX responsive foci.”
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