Microsatellite instability, Epstein–Barr virus, mutation of type II transforming growth factor β receptor and BAX in gastric carcinomas in Hong Kong Chinese

Microsatellite instability (MI), the phenotypic manifestation of mismatch repair failure, is found in a proportion of gastric carcinomas. Little is known of the links between MI and Epstein–Barr virus (EBV) status and clinicopathological elements. Examination of genes mutated through the MI mechanism could also be expected to reveal important information on the carcinogenic pathway. Seventy-nine gastric carcinomas (61 EBV negative, 18 EBV positive) from local Hong Kong Chinese population, an intermediate-incidence area, were examined. Eight microsatellite loci, inclusive of the A10 tract of type II transforming growth factor β receptor (TβR-II), were used to evaluate the MI status. MI in the BAX and insulin-like growth factor II receptor (IGF-IIR) genes were also examined. High-level MI (>40% unstable loci) was detected in ten cases (12.7%) and low-level MI (1–40% unstable loci) in three (3.8%). High-level MI was detected in two EBV-associated cases (11%) and the incidence was similar for the EBV-negative cases (13%). The high-level MIs were significantly associated with intestinal-type tumours (P = 0.03) and a more prominent lymphoid infiltrate (P = 0.04). Similar associations were noted in the EBV-positive carcinomas. The high-level MIs were more commonly located in the antrum, whereas the EBV-associated carcinomas were mostly located in body. Thirteen cardia cases were negative for both high-level MI and EBV. All patients aged below 55 were MI negative (P = 0.049). Of the high-level MIs, 80% had mutation in TβR-II, 40% in BAX and 0% in IGF-IIR. Of low-level MIs, 33% also had TβR-II mutation. These mutations were absent in the MI-negative cases. Of three lymphoepithelioma-like carcinomas, two cases were EBV positive and MI negative, one case was EBV negative but with high-level MI. In conclusion, high-level MIs were present regardless of the EBV status, and were found in a particular clinicopathological subset of gastric carcinoma patient. Inactivation of important growth regulatory genes observed in these carcinomas confirms the importance of MI in carcinogenesis. © 1999 Cancer Research Campaig

Current state of immunotherapy for glioblastoma

Glioma is the most common primary cancer of the central nervous system, and around 50% of patients present with the most aggressive form of the disease, glioblastoma. Conventional therapies, including surgery, radiotherapy, and pharmacotherapy (typically chemotherapy with temozolomide), have not resulted in major improvements in the survival outcomes of patients with glioblastoma. Reasons for this lack of progress include invasive tumour growth in an essential organ, which limits the utility of local therapy, as well as the protection of tumour cells by the blood-brain barrier, their intrinsic resistance to the induction of cell death, and lack of dependence on single, targetable oncogenic pathways, all of which impose challenges for systemic therapy. Furthermore, the unique immune environment of the central nervous system needs to be considered when pursuing immune-based therapeutic approaches for glioblastoma. Nevertheless, a range of different immunotherapies are currently being actively investigated in patients with this disease, spurred on by advances in immuno-oncology for other tumour types. Herein, we examine the current state of immunotherapy for gliomas, notably glioblastoma, the implications for combining the current standard-of-care treatment modalities with immunotherapies, potential biomarkers of response, and future directions for glioblastoma immuno-oncology