Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, India.
Ann Diagn Pathol. 2019 Jun;40:30-39. doi: 10.1016/j.anndiagpath.2019.02.013. Epub 2019 Feb 28.
Most high-grade serous carcinomas (HGSC) of the ovary are advanced stage tumors with early recurrences. However, some tumors do not recur and have a better survival. We identified such cases of HGSC and compared those with the cases that recurred and assessed the relationship between patterns of invasion (intracystic, IC; micropapillary, MP; nonpapillary, NP) with IMP3 and E-Cadherin expression, and evaluated their predictive role in recurrence and survival. The study comprised of seventeen tumors recurred within 18 months of follow-up and 14 cases that did not recur with a minimum follow-up of 49 months. 73% tumors with predominantly MP pattern recurred, while only 27% of non-recurrent tumors showed this pattern. In contrast, predominant NP and IC patterns were seen in 71% of the non-recurrent and in 35% of recurrent tumors. 67.7% tumors expressed IMP3 and all cases expressed E-Cadherin. The tumors with a higher percentage of destructive invasion showed higher IMP3 positivity and greater chances of recurrence, whereas tumors with higher percentage of pushing invasion showed lower IMP3 positivity and lesser chances of recurrence (p = 0.02). IMP3-negative tumors had lower odds of recurrence than IMP3-positive ones (p = 0.01). The patients with negative IMP3 staining had a significantly higher OS than those with IMP3 positive tumors (p = 0.01), regardless of the histologic patterns. Also, reduction in E-Cadherin staining in the metastatic site led to poor DFS (p = 0.016) and OS (p = 0.006). IMP3 may serve as a useful prognostic marker that can stratify patients of advanced stage, high-grade serous carcinomas into two distinct subsets: majority with early recurrence with an infiltrative pattern of invasion and IMP3 positivity particularly in the MP areas; and a smaller subset that do not show early recurrence having pushing borders and are IMP3 negative. Also, E-Cadherin showed significant decrease in expression in the metastatic site of the recurrent cases.
大多数卵巢高级别浆液性癌(HGSC)为晚期肿瘤,早期复发。然而,有些肿瘤不会复发且生存情况较好。我们鉴定了此类 HGSC 病例,并将其与复发病例进行比较,评估了腔内型(IC)、微乳头型(MP)、非乳头型(NP)浸润模式与 IMP3 和 E-钙黏蛋白表达的关系,并评估了它们在复发和生存中的预测作用。本研究包括 17 例在随访 18 个月内复发的肿瘤和 14 例在随访至少 49 个月后未复发的肿瘤。以 MP 为主的肿瘤中 73%复发,而非复发肿瘤中仅 27%为 MP 模式。相比之下,非复发肿瘤中 71%为 NP 和 IC 模式,复发肿瘤中为 35%。67.7%的肿瘤表达 IMP3,所有病例均表达 E-钙黏蛋白。侵袭破坏比例较高的肿瘤表达更高的 IMP3 阳性率和更高的复发机会,而侵袭推进比例较高的肿瘤表达较低的 IMP3 阳性率和较低的复发机会(p=0.02)。IMP3 阴性肿瘤的复发几率低于 IMP3 阳性肿瘤(p=0.01)。IMP3 染色阴性的患者的 OS 明显高于 IMP3 阳性肿瘤患者(p=0.01),无论组织学模式如何。此外,转移部位 E-钙黏蛋白染色减少导致无复发生存期(DFS)较差(p=0.016)和总生存期(OS)较差(p=0.006)。IMP3 可能是一种有用的预后标志物,可将晚期、高级别浆液性癌患者分为两个不同的亚组:大多数患者以浸润性侵袭模式和 IMP3 阳性(特别是在 MP 区域)为主,具有早期复发;一小部分患者没有早期复发,具有推进性边界,IMP3 阴性。此外,复发病例转移部位的 E-钙黏蛋白表达显著下降。