Intratumoral CD8+ Cells Are Strongly and Inversely Correlated with Mitotic Index and Estimated Recurrence-Free Survival in Treatment-Naive Gastric GISTs
Jaclyn F Hechtman, Michael J Donovan, Russell B McBride, Xianzhong Ding, Anli Chen, Lauren Peters, David Chiang, Noam Harpaz. Mount Sinai School of Medicine, New York, NY
Background: There is compelling evidence linking the immune contexture of epithelial and hematologic malignancies to clinical outcomes, but little is known regarding that of GISTs. We investigated whether intratumoral immune cells in untreated gastric GISTs are associated with variables of known prognostic significance.
Design: Immunohistochemistry was performed to identify the number of CD8+ cells, macrophages (CD68+,CD11b+) and presumed regulatory T cells (FOXP3+) in a series of consecutive gastric GIST resection specimens. The number of immunoreactive cells across 10 consecutive HPF was assessed, excluding necrotic tissue and vascular spaces. Associations with mitotic rate (MR), tumor size (TS) and estimated 2-year recurrence-free probability (RFS2) (Gold et al. Lancet Oncol 2009;11:1045-1052) were separately evaluated using generalized linear models in SAS 9.2.
Results: We evaluated 22 GISTs (8 spindle cell, <5mitoses/50 HPF; 10 spindle cell and 4 epithelioid cell, ≥5 mitoses/50 HPF) from 13 males and 9 females, mean age 68.7y (range, 33-91y). Mean TS was 9.3cm (range, 1-27cm). MRs per 50 HPF were: mean 22, median 40, range 1-135. After log-transformation to achieve normality, CD8+ count was correlated with MR (β=-0.72, R2=0.58, p<0.0001) and estimated RFS2 (β=13.8, R2=0.50, p=0.0002). The association between CD8+ cells and MR remained significant after adjustment for TS, age and sex, (β=-0.58, p=0.006); the association with RFS2 remained significant after adjustment for, TS, age, sex and MR (β=3.45, p=0.05). No corresponding correlations with CD3, CD68, CD11b or FOXP3 were identified.
Conclusions: Intratumoral CD8+ cells in gastric GISTs are strongly and inversely correlated with MR and may afford an independent clinical estimate of RFS2. Further study of intratumoral immune regulation should better define its mechanisms and potential therapeutic implications.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 98, Monday Morning