Neuroendocrine tumor arising from the greater omentum treated with laparoscopic tumor resection: a case report

Background Primary omental tumors are extremely rare. Herein, we report the first case of a primary omental neuroendocrine tumor (NET). Case presentation A 59-year-old woman was referred to our hospital for the treatment of an 18-mm tumor located at the ventral side of the duodenum. No other tumor was detected. The preoperative imaging diagnosis was omental tumor. A laparoscopic tumor resection was performed. Histopathological examination revealed that the tumor consisted of cuboidal cells with eosinophilic, granular cytoplasm showing trabecular or ribbon architecture. No other component was seen. The mitotic count was of 5 per 10 high-power fields. Immunohistochemical staining was positive for chromogranin A, synaptophysin, and CD56. Her Ki-67 index was 5%. These results led to the diagnosis of grade 2 omental NET. The patient was discharged on the 3rd postoperative day without any complications and did not develop any recurrence for 3 years. Conclusions We encountered a very rare case of omental NET. Complete resection is recommended with minimally invasive surgery for the diagnosis of NET.

Utilizing porcupine (PORCN) and DKK1 inhibition to improve anti-tumor immunity in a murine model of ovarian cancer.

e18041 Background: Epithelial ovarian cancers (EOC) are immunologically “cold” tumors and consequently have seen limited success with immunotherapy. Wnt-beta/catenin signaling is dysregulated in multiple cancers, including EOC, and is characterized by immune exclusion. Porcupine (PORCN) is the enzyme necessary for secretion of Wnt ligands, which is required for activation of Wnt/beta-catenin signaling. Up-regulation of the Wnt/beta-catenin pathway leads to increased levels of the target gene DKK1, which plays a role in immune exclusion. Our goal is to improve the tumor immune response via targeting Wnt-signaling in EOC. Methods: We utilized a syngeneic murine model (ID8 cell line) deficient in p53 (ID8p53−/−) with and without the addition of a Luciferase tag (Luc+/-) to assess the effect of treatment with a PORCN inhibitor, CGX-1321, with and without DKN-01, a monoclonal antibody targeting DKK1. Mice were treated with vehicle/control, CGX-1321, DKN-01, or CGX-1321/DKN-01. Treatment was given for either 14 or 31 days. In Luc+ mice, bioluminescence imaging was performed weekly. Following mouse sacrifice, omental weights and ascites volume were measured. Omental tumor was used for flow cytometry and representative samples were sent for NanoString analysis. Results: Treatment with CGX-1321 for 14 days reduced omental weight and ascites volume in Luc- mice only (p = 0.02); however, earlier and extended treatment with CGX-1321 and CGX-1321/DKN-01 in Luc+ mice decreased omental weight (p = 0.008 and 0.0025); mice treated with CGX did not develop any ascites with the same treatment schedule. While treatment with DKN-01 alone did not decrease omental weight, treatment with DKN-01 and combination CGX-1321/DKN-01 increased total percentage of NK cells (p = 0.0192 and 0.0070). CGX-1321 and DKN-01 alone and in combination increased the total percentage of CD8+ T cells in omental tumors (p = 0.0238, 0.037, and 0.0127). Conclusions: CGX-1321 decreased omental weight and ascites volume, while DKN-01 increased the cellular percentage of NK cells. Both DKN-01 and CGX-1321 increased CD8+ T cells. Wnt-inhibition is therapeutically promising in EOC, and the combination of a PORCN inhibitor with DKN-01 could improve the response to immune checkpoint blockage and further investigation is warranted.

The role of macrophage production of transforming growth factor-ß in epithelial ovarian cancer progression.

e17100 Background: Increased Transforming Growth Factor- ß (TGF-ß) signaling is associated with poorer prognosis in advanced stage epithelial ovarian carcinoma (EOC). Macrophages are known to produce high amounts of TGF-ß which plays a significant role in immune suppression in the tumor microenvironment Methods: A syngeneic mouse model was created using ID8 cell lines with p53 knocked out. These cells were injected intraperitoneally to establish tumor challenge. One mouse model was treated with TGF-ß monoclonal antibody at the time of tumor inoculation. A second model utilized a mouse line that was engineered to eliminate production of TGF-ß from macrophages specifically. Tumors were harvested and weighed after 42 days of tumor challenge. Flow cytometry was used to analyze differences in CD8 T-cell and T regulatory cell populations. Results: Tumor weights were significantly reduced in mice treated with anti-TGF-ß monoclonal antibody (p = 0.02). Average tumor weights were 125mg vs 101mg comparing non-treated to treated mice. Also, ascites volume was measured using syringe aspiration from peritoneal cavity at the time of sacrifice. Mean ascites volume was 4.7mL vs 2.9 mL (p = 0.004) in untreated mice versus mice treated with monoclonal antibody. In mice with macrophages specific deletion of TGF-ß production, tumors were unable to be established in these mice and omental weights were comparable to tumor naive mice with a mean weight of 34mg compared to 115 mg in wild type mice. In both mouse models there was a significant difference in CD8 : Tregs ratio in omental tumor microenvironment. Conclusions: Increased amounts of TGF-ß contribute to increased tumor invasion and migration, while loss of TGF-ß results in both a decrease in tumor burden and a decrease in suppressors of T cell activity. Inhibition of TGF-ß, demonstrated with a monoclonal antibody can effectively reduce TGF-β signaling. The macrophages within the omental tumor microenvironment are a source of large amounts of TGF-ß and when lost result in an inability to establish tumors in intraperitoneal tumors.