Programmed cell death ligand 1 (PD-L1) is a potential predictive biomarker of the response to anti-PD-L1/anti- programmed cell death 1 (PD-1) therapy in multiple cancers, including triple negative breast cancer(TNBC). The purpose of this study was to investigate whether PD-L1 expression is homogenous in primary tumors(PTs) and synchronous axillary lymph node metastases(LNMs) of TNBC. PD-L1 expression was immunohistochemically evaluated in 101 TNBC patients’ PTs and paired LNMs. PD-L1 expression in tumor cells and infiltrating immune cells or node lymphocytes in the PTs and associated LNMs was scored separately and was correlated with patients’ clinical parameters and prognoses. PD-L1 expression exhibited spatial heterogeneity in both the tumor cells and the infiltrating immune cells or node lymphocytes of PTs and LNMs. The PD-L1 expression levels were significantly higher in the lymphocytes and tumor cells of the LNMs than in the PTs. PD-L1 expression was also more frequent among the LNMs. PD-L1 expression was associated with high grade and more stromal tumor-infiltrating lymphocytes(TILs). Furthermore, the disease-free survival and overall survival were similar between the PT- negative/LNM- positive and PT- positive/LNM- positive patients, both of which exhibited worse disease-free survival(DFS) thanPT -negative/LNM -negative patients. The differential expression of PD-L1 between the PTs and LNMs suggests that LNMs PD-L1 status may be used to indicate whether PD-1/PD-L1-targeted therapy would be suitable for a node-positive TNBC patient in the future.

The aim of our study was to investigate whether an inflammation-based prognostic score, the prognostic nutritional index (PNI), was associated with clinical characteristics and prognosis in patients with high-grade serous ovarian cancer (HGSC). We retrospectively investigated 875 patients who underwent primary staging or debulking surgery for HGSC between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. Preoperative PNI was calculated as serum albumin (g/L) + 0.005 × lymphocyte count (per mm3). The optimal PNI cutoff value for overall survival (OS) was identified using the online tool “Cutoff Finder”. Clinical characteristics and PNI were compared with chi-square or Fisher’s exact tests, as appropriate. The impact of PNI on OS was analyzed using the Kaplan–Meier method and Cox proportional hazards model. The median (range) PNI was 46.2 (29.2–67.7). The 45.45 cutoff value discriminated patients into the high-PNI and low-PNI groups. A low preoperative PNI was associated with an advanced FIGO stage, increased CA125 level, more extensive ascites, residual disease and platinum resistance. For univariate analyses, a high PNI was associated with increased OS (p < 0.001). In multivariate analyses, the PNI remained an independent predictor of OS as a continuous variable (p = 0.021) but not as dichotomized groups (p = 0.346). Our study demonstrated that the PNI could be a predictive and prognostic parameter for HGSC.

It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC). Seven candidate drug-based molecular biomarkers, human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), breast cancer susceptibility gene 2 (BRCA2) and programmed death-ligand 1 (PD-L1) were measured in 96 ovarian CCC and 113 HGSC by immunohistochemistry in paraffin embedded tissues. The relationship between these biomarkers and clinicopathological factors were explored. The expression level of four of the seven drug-based molecular biomarkers was markedly different between HGSC and CCC. High expression levels of HER2 and PD-L1 were more commonly observed in CCC patients (12.6% vs 2.7%, 21.1% vs 11.6%, P = 0.006, 0.064, respectively), while loss of BRCA1 and BRCA2 expression were more frequently occurred in HGSC patients (72.6% vs 54.3%, 89.4% vs 79.8%, P = 0.007, 0.054, respectively). Survival analysis showed that five of seven biomarkers had prognostic values but varied between subtypes. Furthermore, EGFR expressed frequently in CCC patients with endometriosis than in HGSC patients (44.4% vs 8.3%, P = 0.049). AURKA and PD-L1 correlated with the resistance to platinum-based chemotherapy in CCC patients (P = 0.043, 0.028, respectively) while no similar results were observed in HGSC patients. Ovarian CCC showed a markedly different expression map of drug-based molecular biomarkers from HGSC, which suggested a new personalized target therapy in this rare subtype.

Over 20 % of ovarian cancer patients have preoperative thrombocytosis or hyperfibrinogenemia. We aimed to demonstrate the clinical and prognostic significance of thrombocytosis and hyperfibrinogenemia in high-grade serous ovarian cancer (HGSC). We retrospectively investigated HGSC patients who underwent primary staging or debulking surgery between April 2005 and June 2013 in our institution. None of these patients had received neoadjuvant chemotherapy. Data, including age, performance status, FIGO stage, serum CA125, platelet count, fibrinogen level, and surgical residual disease, were collected. Thrombocytosis was defined as a platelet count greater than 450 × 109/L, and hyperfibrinogenemia was defined as a fibrinogen level higher than 4.00 g/L. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For the multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which are expressed as hazard ratios (HRs). A total of 875 consecutive HGSC patients were identified. The median follow-up time was 29 (1–115) months. The median (interquartile range, IQR) preoperative platelet count was 301 (235–383) × 109/L, and 121 (13.8 %) women had thrombocytosis. The median (IQR) preoperative fibrinogen level was 3.85 (3.19–4.45) g/L, and 332 (45.9 %) of the patients had hyperfibrinogenemia. Both preoperative thrombocytosis and hyperfibrinogenemia were associated with an advanced FIGO stage (p = 0.008 and <0.001, respectively), an increased CA125 level (p = 0.004 and 0.001, respectively), more extensive ascites (p < 0.001 and <0.001, respectively), more extensive residual disease (p < 0.001 and <0.001, respectively) and chemosensitivity (p = 0.043 and <0.001, respectively). In the univariate analyses, hyperfibrinogenemia was associated with reduced PFS (p < 0.001) and OS (p < 0.001). However, thrombocytosis was not found to be a potential predictor of PFS (P = 0.098) or OS (p = 0.894). In the multivariate analyses, hyperfibrinogenemia was an independent predictor of OS (p = 0.014) but not PFS (p = 0.062). Preoperative thrombocytosis and hyperfibrinogenemia reflected tumor burden to some extent and thus influenced treatment outcomes, and the fibrinogen level was found to be useful as a prognostic predictor in the HGSC patients.

Background: Defects in DNA damage repair (DDR) system may lead to genomic instability and manifest as increased immunogenicity. DDR deficiency is prevalent in ovarian cancer (OvCa); however, the association of DDR mutation with immune profiles in OvCa remains largely unknown. This knowledge will provide an essential basis to the rational design of biomarker‐guided immune combination therapy of OvCa in the future.Methods: Whole‐exome sequencing data of 587 OvCa from The Cancer Genome Atlas (TCGA) were used to determine the expression profiles of 47 immune‐related genes and the abundance of tumor‐infiltrating immune cells. A Chinese OvCa cohort (n = 220) tested by next‐generation sequencing (NGS) was used to validate the association between DDR status and tumor mutation burden (TMB).Results: A total of 19.3% in TCGA cohort and 25.9% in Chinese cohort harbored at least one DDR somatic mutation. DDR deficiency exhibited a distinct immune profile with significant higher expression levels of PTPRCAP, CCL5, IFI16, LAG3, IL15RA, and GBP1 in OvCa in the TCGA cohort. Different DDR pathway deficiency displayed various immune profiles. Increased levels of Th1 cells, TMB, and neoantigen were also observed in DDR‐deficient tumors.Conclusions: DDR deficiency was associated with specific immune signatures in OvCa. Our findings emphasize the urgent need for biomarker‐guided rational immune combination therapy to maximize the OvCa patients who could benefit from immunotherapy.