Novel Criteria for Intratumoral Budding with Prognostic Relevance for Colon Cancer and Its Histological Subtypes.
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ABSTRACT:
SUBMITTER: Pour Farid P
PROVIDER: S-EPMC8658236 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent data indicate that tumor-associated neutrophils (TANs) serve a dual role in tumor progression and regression. CD66b is a neutrophil marker and has been associated with patient outcome in various cancers. However, its clinical impact in non-small cell lung cancer (NSCLC) remains controversial. 536 NSCLC patients, of which 172 harbored lymph node metastases, were included in this study. Tissue microarrays were constructed and multiplexed immunohistochemistry of CD66b, CD34 and pan-keratin was performed to evaluate the localization and quantity of CD66b+ TANs. High intratumoral CD66b+ TANs density in squamous cell carcinoma (SCC) subgroup was an independent positive prognosticator for disease-specific survival (P = 0.038). In contrast, high intratumoral TANs density was an independent negative prognostic factor in the adenocarcinoma (ADC) subgroup (P= 0.032). Likewise, in ADC patients with lymph node metastases, high level of intratumoral TANs was associated with poor prognosis (P = 0.003). Stromal CD66b+ TANs were not associated with outcome of NSCLC patients. In conclusion, CD66b+ TANs show diverging prognostic effect in NSCLC patients according to histological subgroups. The presence of CD66b+ TANs could prove pivotal for development of an immunoscore in ADC NSCLC patients.
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Project description:ImportanceObesity is associated with increased risk of colorectal cancer (CRC) and a more aggressive disease course. Tumor budding (TB) is an important prognostic factor for CRC, but its association with obesity is unknown.ObjectiveTo evaluate the association of TB with obesity and other prognostic factors in colon cancer.Design, setting, and participantsThis cohort study involved a histological review of colon cancer specimens obtained during 7 years (January 2008 to December 2015) at the University of Kentucky Medical Center; data analysis was conducted from February 2020 to January 2021. Specimens came from 200 patients with stage I to III colon cancer; patients with stage 0, stage IV, or incomplete data were excluded.Main outcomes and measuresTB was defined as 1 to 4 malignant cells at the invasive edge of the tumor, independently assessed by 2 academic pathologists. The primary outcome was the association of TB with obesity (defined as body mass index [BMI] of 30 or greater). Secondary outcomes include the association of TB with clinical features (ie, age, race, sex, TNM stage, tumor location) and pathological features (ie, poorly differentiated tumor clusters [PDCs], Klintrup-Mäkinen inflammatory score, desmoplasia, infiltrative tumor border, tumor necrosis, and tumor-to-stroma ratio).ResultsA total of 200 specimens were reviewed. The median (interquartile range) age of patients was 62 (55-72) years, 102 (51.0%) were women, and the mean (SD) BMI was 28.5 (8.4). A total of 57 specimens (28.5%) were from stage I tumors; 74 (37.0%), stage II; and 69 (34.5%), stage III. Of these, 97 (48.5%) had low-grade (<5 buds), 36 (18.0%) had intermediate-grade (5-9 buds), and 67 (33.5%) had high-grade (≥10 buds) TB. Multivariable analysis adjusting for clinical and histological factors demonstrated that higher TB grade was associated with obesity (odds ratio [OR], 4.25; 95% CI, 1.95-9.26), higher PDC grade (grade 2 vs 1: OR, 9.14; 95% CI, 3.49-23.93; grade 3 vs 1: OR, 5.10; 95% CI, 2.30-11.27), increased infiltrative tumor border (OR, 1.03; 95% CI, 1.01-1.04), cecal location (OR, 2.55; 95% CI, 1.09-5.97), and higher stage (eg, stage III vs stage I for high-grade or intermediate-grade vs low-grade TB: OR, 2.91; 95% CI, 1.00-8.49). Additionally, patients with a higher TB grade had worse overall survival (intermediate vs low TB: hazard ratio, 2.20; 95% CI, 1.11-4.35; log-rank P = .02; high vs low TB: hazard ratio, 2.67; 95% CI, 1.45-4.90; log-rank P < .001).Conclusions and relevanceIn this cohort study, a novel association between high TB grade and obesity was found. The association could reflect a systemic condition (ie, obesity) locally influencing aggressive growth (ie, high TB) in colon cancer.
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Project description:Classical Hodgkin lymphoma (cHL) is a highly curable disease, with about 80% of patients cured using standard first-line chemotherapy. However, outcomes for relapsed/refractory patients re-main unfavorable and there is a critical lack of predictive biomarkers for early identification of these patients who may benefit from new therapeutic strategies. Here we evaluated the dynamic expression of 571 immune-related genes in a cohort of 42 cHL using NanoString technology. We identified a 19-genes immune signature predictive of relapse at the time of diagnosis, which was found to be strongly dependent on histological subtype. Moreover, comparative analyses be-tween paired diagnostic/relapsed biopsies of nodular sclerosis cHL showed 134 differentially expressed genes, highlighting an immune contexture shift at relapse not found in the mixed-cellularity subtype. Overall, these results strongly suggest that the predictive value of immune signature in cHL is influenced by histological subtype, a criterion that should be con-sidered when assessing new immunotherapy strategies.
2022-10-10 | GSE212902 | GEO
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2016-08-17 | GSE62165 | GEO
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