Journal
CANCER
Volume 101, Issue 12, Pages 2779-2787Publisher
WILEY
DOI: 10.1002/cncr.20701
Keywords
high-density tissue microarray; migrated monocytes; monocyte chemoattractant protein 1; tumor aggressiveness; squamous cell carcinoma; head and neck cancer
Categories
Funding
- NCI NIH HHS [R01 CA094121-03, R01 CA094121, 1P50 CA/DE97248-01] Funding Source: Medline
Ask authors/readers for more resources
BACKGROUND. The survival of patients with head and neck squamous cell carcinoma (HNSCC) remains unaffected despite recent therapeutic advances. To reverse this trend, reliable and clinically applicable markers of tumor aggressiveness must be identified. One such marker may be the tumor-associated macrophage content. The authors hypothesized that tumor-associated macrophages contribute to HNSCC aggressiveness, and the objective of the current study was to prove this hypothesis using mRNA expression analysis and a large cohort of clinical specimens. METHODS. Oligonucleotide microarray analysis was performed on a prospective cohort of 20 patients with previously untreated oral cavity or oropharynx squamous cell carcinoma (OC/OP SCCA) and on normal oropharyngeal mucosa from 4 patients. After determining whether macrophage chemoattractants were produced by tumors, conditioned media from three HNSCC cell lines were used to quantify macrophage migration in an in vitro assay. A high-density tissue microarray of 102 patients with previously untreated OC/OP SCCA was stained immunohistochemically for CD68 to identify tissue macrophages, and the results were correlated with clinicopathologic data and survival. RESULTS. Monocyte chemoattractant protein 1 was up-regulated significantly in tumors compared with normal mucosa (P = 0.0025; fold change = 1.89). All University of Michigan SCC tumor cell line conditioned media caused a significant increase in macrophage migration (P < 0.05). Tissue microarray data revealed that macrophage content of the primary tumor was associated strongly with lymph node metastasis (P < 0.0001), extracapsular lymph node spread (P = 0.0001), and advanced clinical disease stage (P = 0.0002). when it was evaluated along with other clinicopathologic data, the macrophage content was found to be an independent predictor of lymph node metastasis (P < 0.0001). CONCLUSIONS. Primary tumor macrophage content is a strong predictor of tumor aggressiveness in HNSCC. (C) 2004 American Cancer Society.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available