Immune Responses Vary in Preinvasive Colorectal Lesions by Tumor Location and Histology.

Immune responses vary in colorectal cancers, which strongly influence prognosis. However, little is known about the variance in immune response within preinvasive lesions. The study aims to investigate how the immune contexture differs by clinicopathologic features (location, histology, dysplasia) associated with progression and recurrence in early carcinogenesis. We performed a cross-sectional study using preinvasive lesions from the surgical pathology laboratory at the Medical University of South Carolina. We stained the tissues with immunofluorescence antibodies, then scanned and analyzed expression using automated image analysis software. We stained CD117 as a marker of mast cells, CD4/RORC to indicate Th17 cells, MICA/B as a marker of NK-cell ligands, and also used antibodies directed against cytokines IL6, IL17A, and IFNγ. We used negative binomial regression analysis to compare analyte density counts by location, histology, degree of dysplasia adjusted for age, sex, race, and batch. All immune markers studied (except IL17a) had significantly higher density counts in the proximal colon than distal colon and rectum. Increases in villous histology were associated with significant decreases in immune responses for IL6, IL17a, NK ligand, and mast cells. No differences were observed in lesions with low- and high-grade dysplasia, except in mast cells. The lesions of the proximal colon were rich in immune infiltrate, paralleling the responses observed in normal mucosa and invasive disease. The diminishing immune response with increasing villous histology suggests an immunologically suppressive tumor environment. Our findings highlight the heterogeneity of the immune responses in preinvasive lesions, which may have implications for prevention strategies. PREVENTION RELEVANCE: Our study is focused on immune infiltrate expression in preinvasive colorectal lesions; our results suggest important differences by clinicopathologic features that have implications for immune prevention research.

Platelet and hemoglobin count at diagnosis are associated with survival in African American and Caucasian patients with colorectal cancer.

BACKGROUND: African Americans (AAs) compared to Caucasian Americans (CAs) with colorectal cancer (CRC) have lower stage-specific survival. CRC patients often present with several hematopathologies (such as thrombocytosis, thrombocytopenia, anemia) at diagnosis, which is associated with poorer survival. However, whether these measures impact the racial disparity in survival is not known. METHODS: The study population was composed of 581 histologically confirmed CRCs at the Medical University of South Carolina (393 CA, 188 AA) diagnosed between 01/01/2000 and 06/30/2013. We used Cox proportional hazards regression to estimate the association between thrombocytosis, thrombocytopenia, or anemia at diagnosis and risk of death by race. This analysis was adjusted for age, sex, stage and first-line treatment. RESULTS: In all patients combined, thrombocytosis, thrombocytopenia, and anemia (vs. the normal ranges) were associated with significantly higher risks of death. In the race-specific analyses, AAs (HR 2.51 [95 % CI: 1.52-4.15]) vs. CAs (HR 1.15 [95 % CI: 0.75-1.75]) with thrombocytosis compared to normal had a higher risk of death (p for difference = 0.03). CONCLUSIONS: Abnormal thrombocyte and hemoglobin levels at diagnosis were associated with poorer survival. AAs compared to CAs with elevated platelets at diagnosis had a higher risk of death. Our study is the first to examine the role of race, hematologic measures at diagnosis, and risk of death in colorectal cancer patients. These results suggest that the racial differences in the immune response may contribute to the racial disparity in survival.