ANALYSIS OF INTERLEUKIN-6 GENE-EXPRESSION IN CERVICAL NEOPLASIA USINGA QUANTITATIVE POLYMERASE CHAIN-REACTION ASSAY - EVIDENCE FOR ENHANCED INTERLEUKIN-6 GENE-EXPRESSION IN INVASIVE-CARCINOMA

Interleukin 6 (IL-6) is a multifunctional cytokine which has recently been shown to act kt vitro as a growth factor for cervical carcinoma c ell lines. This prompted us to measure IL-6 gene expression using a ne w quantitative polymerase chain reaction assay in 13 invasive cervical cancers, 5 eases of cervical intraepithelial neoplasia, and 2 normal cervix. A significant increase in the expression of the IL-6 gene in i nvasive cervical carcinoma as compared to cervical intraepithelial neo plasia and normal cervix was demonstrated (P < 0.05). Unlike IL-6, the expression of other cytokine genes such as gamma-interferon was not c orrelated with any particular cervical histological lesion. Immunohist ochemical analysis identified IL-6 protein only on stroma cells which, based on morphological criteria, most likely belong to the macrophage lineage. This was reinforced by the correlation observed between IL-6 gene expression and macrophage tumor infiltration (P < 0.007). No IL- 6 immunostaining of cervical tumor cells was shown. Therefore this stu dy confirms, ill vivo, that IL-6 may play a role in the pathogenesis o f carcinoma of the uterine cervix since its increased expression is as sociated with advanced neoplastic cervical lesions. In contrast to in vitro studies, the stromal origin of IL-6 suggests that this cytokine may modulate tumor cell proliferation by a paracrine rather than an au tocrine mechanism.