Tumor budding correlates with the protumor immune microenvironment and is an independent prognostic factor for recurrence of stage I lung adenocarcinoma Journal Article

   

Authors:	Kadota, K.; Yeh, Y. C.; Villena-Vargas, J.; Cherkassky, L.; Drill, E. N.; Sima, C. S.; Jones, D. R.; Travis, W. D.; Adusumilli, P. S.
Article Title:	Tumor budding correlates with the protumor immune microenvironment and is an independent prognostic factor for recurrence of stage I lung adenocarcinoma
Abstract:	BACKGROUND: Immune cell infiltration associated with tumor capsule disruption and tumor budding has been shown to reflect invasiveness, metastasis, and unfavorable prognosis in colorectal cancer. We investigated the influence of tumor budding on prognosis and its association with the immune microenvironment in lung adenocarcinoma. METHODS: Tumor slides from resected stage I lung adenocarcinomas were reviewed (n=524 and n=514, for training and validation cohorts, respectively) for assessment of tumor budding. CD3+ and forkhead box P3+ (FoxP3+ ) lymphocytes, CD68+ macrophages, IL-7 receptor, and IL-12 receptor b 2 were analyzed using tissue microarrays constructed from tumor and stroma. Probability of recurrence was calculated using the competing risks method. RESULTS: In the training cohort, risk of recurrence for high-grade tumor budding was higher than it was for low-grade tumor budding (32% vs 12%, P < .001), which was confirmed in the validation cohort ( P=.005). Tumor budding stratified the risk of recurrence for acinar-predominant (22% vs 9%, P <.001), papillary-predominant (22% vs 13%, P=.045), and solid-predominant (39% vs 19%, P=.022) tumors. Tumor budding was associated with higher stromal FoxP3+ lymphocyte infiltration, higher stromal FoxP3/CD3 risk index, higher tumoral and stromal CD68 1 macrophage infiltration, and IL-7 receptor overexpression ( P < .001, all associations). Tumor budding remained independently associated with recurrence on multivariate analysis (hazard ratio, 1.61; P=.008). CONCLUSIONS: Tumor budding is an independent prognostic factor of stage I lung adenocarcinoma and correlates with the protumor immune microenvironment. Our findings advocate investigating tumor-immune cell interactions at the invading edge as a biologic driver of tumor aggressiveness. © 2015 American College of Chest Physicians.
Keywords:	adult; cancer survival; controlled study; human tissue; aged; survival rate; major clinical study; overall survival; cancer recurrence; cancer risk; validation process; conference paper; cancer staging; recurrence risk; cancer grading; transcription factor foxp3; disease association; gene overexpression; cohort analysis; survival time; lung adenocarcinoma; tumor immunity; tissue microarray; papillary carcinoma; lymphocytic infiltration; cd3+ t lymphocyte; colloid carcinoma; acinar cell carcinoma; cell interaction; oncogenesis and malignant transformation; cd68 antigen; tumor microenvironment; interleukin 7 receptor; tumor budding; cancer prognosis; interleukin 12 receptor beta2; human; male; female; priority journal
Journal Title:	Chest
Volume:	148
Issue:	3
ISSN:	0012-3692
Publisher:	American College of Chest Physicians
Date Published:	2015-09-01
Start Page:	711
End Page:	721
Language:	English
DOI:	10.1378/chest.14-3005
PROVIDER:	scopus
PMCID:	PMC4556124
PUBMED:	25836013
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84940111608&partnerID=40&md5=7e4e0b791d8727fb3d8bbf7f9af33a71
Notes:	Export Date: 2 October 2015 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/81178