A tumor microenvironment-based classification of gastric cancer for more effective diagnosis and treatment.

With approximately one million diagnosed cases and over 700,000 deaths recorded annually, gastric cancer (GC) is the third most common cause of cancer-related deaths worldwide. GC is a heterogeneous tumor. Thus, optimal management requires biomarkers of prognosis, treatment selection, and treatment response. The Cancer Genome Atlas program sub-classified GC into molecular subtypes, providing a framework for treatment personalization using traditional chemotherapies or biologics. Here, we report a comprehensive study of GC vascular and immune tumor microenvironment (TME)-based on stage and molecular subtypes of the disease and their correlation with outcomes. Using tissues and blood circulating biomarkers and a molecular classification, we identified cancer cell and tumor archetypes, which show that the TME evolves with the disease stage and is a major determinant of prognosis. Moreover, our TME-based subtyping strategy allowed the identification of archetype-specific prognostic biomarkers such as CDH1-mutant GC and circulating IL-6 that provided information beyond and independent of TMN staging, MSI status, and consensus molecular subtyping. The results show that integrating molecular subtyping with TME-specific biomarkers could contribute to improved patient prognostication and may provide a basis for treatment stratification, including for contemporary anti-angiogenesis and immunotherapy approaches.

A Morphological and Immunohistochemical Study of the Tumoral and Inflammatory Cells in Pancreatic Ductal Adenocarcinoma.

This study is aimed at investigating tumoral and inflammatory cells and the significance of the prognostic factors of pancreatic ductal adenocarcinoma (PDAC); it is also aimed at determining the role of immunohistochemistry in the diagnosis and prognosis of this neoplasm. Materials and Methods. 230 cases of pancreatic ductal adenocarcinoma were included in the study group; these cases were selected from the archives of the Department of Pathology of the Fundeni Clinical Institute over a ten-year period. Immunohistochemistry was performed using the following antibodies: MUC 1, CD 34, Factor VIII, CD 68, MMP-7, CEA, p21, p53, and Ki 67. Results. There were 133 male (57.8%) and 97 female (42.2%) patients included in this study, with ages between 20 and 81 years old (mean age: 58.2 years) and with tumors located in the pancreatic head (n = 196; 85.2%), pancreatic body (n = 12; 5.2%), and pancreatic tail (n = 20, 8.7%), as well as panpancreatic tumors (n = 2; 0.9%). Patients presented with early stages (IA and IB), with low pathologic grade (G1), with small size tumors (less than 1-1.5 cm), with tumors located in the head of the pancreas, (p53: negative; p21: positive; and CD 68: positive in peritumoral tissue), with low nuclear index (Ki 67 < 10%), without metastases at the time of surgery (had a better prognosis), and with a survival rate of about 7 months. Conclusions. Immunohistochemistry is useful for an accurate diagnosis, differential diagnosis, and establishment of additional factors that might have a prognostic importance. It is recommended to study peritumoral tissue from the quantitative and qualitative points of view to increase the number of prognostic factors. This study represents a multidisciplinary approach, and it is a result of teamwork; it presents histopathological methods of examination of this severe illness and describes only a part of the scientific effort to determine the main pathological mechanisms of this neoplasm.

Gastrointestinal stromal tumors of the colon and rectum.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms, colorectal location being met in less than 5% of cases. Knowledge about this site related particularities are limited. The aim of this study is to present our experience with colorectal GISTs between 2005 and 2018 from the clinical, morphological, and immunohistochemical perspectives, with emphasis on prognostic factors. From a total of 203 gastrointestinal stromal tumors registered, 12 were colorectal (6%). The number of colonic tumors surpassed that of the rectum (9 : 3) and on the right side were registered more cases than on the left side (6/3). 9 were primary tumors and 3 were recurrences. Men and women were represented equally and the age range was between 22 and 76. Tumor dimensions varied between 0.5 and 14 cm. Microscopically, spindle cell type was dominant. Mitotic rate was variable between 1 and 115/50HPFs. Accordingly, for primary tumors progression risks were assigned (low risk: 2 cases, intermediate risk: 3 cases and high risk: 4 cases). All GISTs were CD117 and DOG1 positive. Four of the patients died of the disease.