Coindre Jm

The prognostic significance of several histologic features of the primary tumors and regional lymph nodes was analyzed in 82 consecutive patients with carcinoma of the colon and rectum. Three criteria were shown to have a statistically significant favorable impact on prognosis: Dukes' A or B stage, the absence of mucinous components and the presence of lymphoplasmocytic infiltration in or around the tumor. Based upon the number of these criteria present, we were able to separate the patients into three distinct prognostic groups. We suggest that such a grouping is simple and should be considered in the design and analysis of future adjuvant trials done for carcinoma of the colon and rectum.

Soft tissue sarcomas are a group of rare and aggressive connective tissue neoplasms for which curative therapeutic opportunities are limited in advanced phase. Clinical trials assessing immunotherapy in these tumors have so far reported limited efficacy. The objective of this study is to provide a description of the immunologic landscape of sarcomas to guide the next clinical trials of immunotherapy in these diseases. The gene expression profile of 93 immune checkpoint (ICP) and membrane markers (MM) of immune cells was analyzed in a series of 253 soft tissue sarcoma (synovial sarcoma, myxoid liposarcoma, sarcoma with complex genomic and GIST) using Agilent Whole Human Genome Microarrays. The unsupervised hierarchical clustering of gene expression level was found able to properly group patients according to the histological subgroup of sarcoma, indicating that each sarcoma subgroup is associated with a specific immune signature defined by its gene expression pattern. Using the prognostic impact of CIBERSORT signature on metastatic-free survival in each subgroup, specific target could be proposed for each of the four groups: Treg through ICOS and GITR in GIST, M0 macrophages in all four sarcoma subtypes, OX40 in SS, CD40 in GIST and SS. The immune landscape of sarcoma was found to be as heterogeneous as the histotypes and molecular subtypes, but strongly correlated to the histotype. Histotype adapted immunotherapeutic approaches in each sarcoma subtypes must be considered in view of these results, consistently with the already reported specific response of histotypes of ICPs.

BACKGROUND: KIT exon 11 mutations are observed in 60% of gastrointestinal stromal tumours (GIST). Exon 11 codes for residues Tyr568 and Tyr570, which play a major role in signal transduction and degradation of KIT. Our aim was to compare the outcome of patients with deletion of both Tyr568-570 (delTyr) and the most frequent deletion delWK557-558 (delWK). METHODS: Pathology and clinical characteristics of 68 patients with delTyr (n=26) or delWK (n=42) were reviewed and compared. RESULTS: GISTs with delTyr were more frequently extragastric than those with delWK (69 vs 26%, P<0.0005). After curative surgery, median relapse-free survival were 10.8 and 11.1 months for patients with delTyr (n=14) and delWK (n=29), respectively (P=0.92). All patients treated with imatinib for a non-resectable or metastatic GIST had an objective response (n=15) or a stable disease (n=21) as best response, regardless of mutation. Median progression-free survival with imatinib were 21.9 and 18.9 months for patients with GIST with delTyr (n=14) and delWK (n=22), respectively (P=0.43). CONCLUSION: In this large retrospective series, the type of KIT exon 11 mutation was correlated with the origin of GIST, but not with prognosis or response to imatinib.