Macrophage migration inhibitory factor contributes angiogenesis by up-regulating IL-8 and correlates with poor prognosis of patients with primary nasopharyngeal carcinoma.
OBJECTIVE
We aim at the association of macrophage migration inhibitory factor (MIF) with neovascularization and survival of nasopharyngeal carcinoma (NPC), and determine whether MIF is a valuable prognostic predictor for NPC patients.


METHODS
One hundred and forty one cases of NPC and 25 normal tissues of nasopharynx were collected. The expression of MIF and interleukin 8 (IL-8) was evaluated in tissues microarray by immunostaining. Intratumoral microvessel density (IMD) in relation to immunostainings and clinicopathological factors were analyzed statistically as well as the follow-up data of patients.


RESULTS
High-expression of both MIF (69.5%) and IL-8 (56.0%) were significantly associated with increased microvessels and lymph node metastasis. High-expression of MIF, IL-8 and higher level of IMD were correlated with either patients' overall survival or disease-specific survival in univariate analysis, but only angiogenesis and lymph node status exhibited in relation to survival of patients as independent prognostic factor of NPC by multivariate analysis. In addition, high-expression of MIF and higher level of IMD were closely associated with locoregional failure of NPC patients.


CONCLUSIONS
MIF may contribute to lymph node metastasis in NPC by inducing angiogenesis through the way of upregulation of IL-8 expression in an autocrine EBV-independent pathway.
Liao
Bing
B
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Zhong
Bi-ling
BL
Li
Zhi
Z
Tian
Xiao-ying
XY
Li
Yang
Y
Li
Bin
B
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D009305:Nasopharynx / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
D016209:Interleukin-8; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human