Expression of IL-32 in human lung cancer is related to the histotype and metastatic phenotype.
BACKGROUND
A strong link has been recently demonstrated between inflammation and lung cancer. Thus, we investigated whether the proinflammatory cytokine IL-32 may be involved in lung carcinogenesis and hence provide a novel therapeutic target.


OBJECTIVE
Lung cancer subtypes display different clinical outcomes. We have set out to clarify the role of IL-32 in the physiopathology of the main histotypes.


METHODS
IL-32 expression, as visualized by immunohistochemistry on 23 premalignant and 148 malignant lesions, was correlated with clinicopathological and survival data. Confocal microscopy, microdissection, and real-time reverse transcription-polymerase chain reaction were used to identify cell sources and expression levels of IL-32.


RESULTS
IL-32 expression was lacking in the majority of squamous-cell carcinomas (SCC) (76%) and their precursor lesions, but strongly up-regulated in most adenocarcinomas (AC) (73%) and their precursors, 64% of large-cell carcinomas, and 77% of small-cell lung cancers. Lymph node metastases frequently developed from IL-32-expressing lung cancers, and especially (82%) from those endowed with an IL-32-expressing leukocyte infiltrate (TIL) mainly composed of CD68(+) macrophages, CD4(+) T lymphocytes, and DC-SIGN(+) dendritic cells. Expression levels of IL-32 by both TIL and tumor cells (TC), particularly in AC and SCC, were paralleled by those of IL-6, IL-8, and vascular endothelial growth factor in the same cell population and correlated with high intratumor microvessel density and poor clinical outcome.


CONCLUSIONS
IL-32 is probably implicated in the pathogenesis of most lung cancer histotypes but unlikely in that of SCC. Its TIL and TC expression are both associated with acquisition of an invasive and metastatic phenotype and may be a useful prognostic indicator.
Sorrentino
Carlo
C
Department of Oncology and Neurosciences, Anatomic Pathology Section, G. d'Annunzio University, Italy. .
Di Carlo
Emma
E
D000368:Aged; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism
C496971:IL32 protein, human; D007378:Interleukins; D012333:RNA, Messenger