Abstract 747: Pak1, TGFα, Ki 67 and survival in human gastric and gastroesophageal junction adenocarcinomas

Stomach cancer is the third most common cause of cancer mortality worldwide. Most are adenocarcinomas. Adenocarcinomas of the stomach fall into two obvious groups based on site of origin; those arising in the area of the gastroesophageal junction (GEJ) and those arising from a more distal location, which we term gastric in this study. Adenocarcinomas of the stomach fall into four obvious groups based on a combination of genomic, molecular biologic, clinical and histopathologic characteristics (Nagara A, Kikuchi O, Bass AJ, Cancer Discovery 2019; DOI: 10.1158/2159-8290.CD-19-0487). We are reporting herein a study of 99 patients with adenocarcinoma of the stomach. This study evaluates the location of the tumor, the histopathologic features of the tumor, the immunohistochemically determined nuclear and cytoplasmic expression of P21 activated kinase (Pak 1), Transforming Growth Factor α (TGFα), and Ki67, a marker of cell proliferation. This study correlates these findings with patient survival. The study reveals: 1. significantly lower survival in patients with diffuse type adenocarcinoma compared to intestinal type, in both GEJ and gastric locations. 2. both GEJ and gastric adenocarcinomas had a poor prognosis. 3. increased expression of both TGFα and Pak1 in GEJ adenocarcinomas. 4. Ki67 expression is significantly less in diffuse type than the intestinal type (p=0.01 for GEJ and 0.03 for gastric). 5. cytoplasmic Pak1 and cytoplasmic TGFα were highly positively correlated (p=0.0001). 6. Ki67 expression was significantly inversely correlated with both nuclear Pak1 (p=0.04) and nuclear TGFα (p=0.02). 7. significantly increased expression of nuclear Pak1 in gastric diffuse type compared with gastric intestinal (p=0.0002) and GEJ intestinal (p=0.0001). These data suggest that Pak1 and TGFα might serve as diagnostic biomarkers of subtypes of adenocarcinomas of the stomach and gastroesophogeal junction. Citation Format: Larry E. Douglass, Michael Parritt, Adam Neltner, Mariah Dooley, Michelle Robillard, Molly Frydl, Leah Focke, Kyle Damen, James A. Deddens, Julia H. Carter. Pak1, TGFα, Ki 67 and survival in human gastric and gastroesophageal junction adenocarcinomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 747.