PD-L1 Expression Predicts a Distinct Prognosis in Krukenberg Tumor with Corresponding Origins.

Haiyan Tai,Zhigang Zhang,Zhiyong Wu,Yanfeng Xi,Congjian Xu,Su’An Sun,Qin Yang,Ran Zhao,Rui Cao,Mengyu Zhang

doi:10.1155/2018/9485285

Abstract

Krukenberg tumor (KT) is an uncommon ovarian metastatic signet-ring cell adenocarcinoma that mostly metastasizes from gastrointestinal carcinoma. Optimal treatment options for KTs are limited. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have shown remarkable activity in clinical trials for metastatic tumors. Here, we evaluated PD-L1 expression and T cell infiltration in KTs and their corresponding primary tumors. Positive tumor PD-L1 expression was detected in 9 (25.7%) KTs from gastric carcinomas (GCs) and in 20 (66.7%) KTs from colorectal carcinomas (CRCs). Patient survival was assessed according to the PD-L1 status and CD8+ T cell density. Positive tumor PD-L1 expression in KTs from GCs was associated with poor prognosis. In contrast, positive tumor PD-L1 expression in KTs from CRCs was associated with an improved prognosis. We analyzed copy number variations of the PD-L1 gene in KTs. PD-L1 expression was higher in cases with copy number gains. The T cell densities within KTs and their corresponding primary tumors were compared. The densities of CD8+ T cells correlated significantly between the primary tumors and KTs from the same case. Taken together, the research further highlighted targets for immune-based therapy in KTs from GCs and CRCs.

Highlights

Ovarian metastatic tumors that contain a component of signet-ring cells are known as Krukenberg tumors (KTs) and originate mainly from the stomach (76%), intestines (11%), breast (4%), and other organs [1]
A tissue microarray was constructed for paraffin sample tissues and included 35 KTs with 23 matched primary gastric carcinomas (GCs) and 30 KTs with 28 matched primary CRCs collected at Fudan University Affiliated Obstetrics and Gynecology Hospital and cooperative hospitals between 2000 and 2015
In KTs from GCs, positive tumor programmed death-ligand 1 (PD-L1) expression was associated with poor prognosis

Summary

Introduction

Ovarian metastatic tumors that contain a component of signet-ring cells are known as Krukenberg tumors (KTs) and originate mainly from the stomach (76%), intestines (11%), breast (4%), and other organs [1]. A few studies have suggested that patients might benefit from metastasectomy with systemic chemotherapy, optimal treatment options are limited and the prognosis is poor [2,3,4]. The need for new strategies to treat KTs is pressing. Immunotherapy has emerged as a promising measure for cancer treatment [6]. Accumulative data have revealed the successful application of immune checkpoint blockers in multiple cancer types, including advanced gastrointestinal carcinoma [7,8,9,10]. High response rates to PD-1 inhibitors were observed among advanced colorectal carcinoma (CRC) and gastric carcinoma (GC) patients whose tumors were mismatch repair-deficient [10].

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Conclusion