title: The absence of CCL2 expression in cervical carcinoma is associated with increased survival and loss of heterozygosity at 17q11.2.
abstract: To determine whether CCL2 mRNA expression is beneficial or detrimental for cervical cancer patients, the association between the expression of this molecule by cervical tumour cells, the number of tumour-associated macrophages, and clinicopathological parameters such as recurrence, relapse-free survival, and overall patient survival was investigated. In cervical cancer samples from 93 untreated cervical cancer patients, the CCL2 mRNA expression level was quantified using RNA in situ hybridization and verified using real-time quantitative RT-PCR. The number of tumour-associated macrophages was determined using immunohistochemistry. Furthermore, the study investigated whether lack of CCL2 expression was due to genetic alterations near the 17q11.2 (CCL2 genomic) region. CCL2 mRNA expression by cervical tumour cells was associated with the number of tumour-associated macrophages (p < 0.001). Lack of CCL2 mRNA expression (15 samples; 16%) was associated with increased cumulative relapse-free survival (log rank test, p = 0.030), increased cumulative overall survival (log rank test, p = 0.024), less post-operative surgery, reduced local and distant recurrence, reduced vascular invasion, and smaller tumour size (<40 mm). The absence of CCL2 mRNA expression corresponded with loss of heterozygosity (LOH) at 17q11.2 in five of six samples. The increased cumulative relapse-free survival and cumulative overall survival of cervical cancer patients lacking tumour cell-associated CCL2 mRNA suggest that the tumour-associated macrophages support tumour progression, presumably by promoting angiogenesis and production of growth factors.
authors.affiliation: Department of Gynecology, Leiden University Medical Centre, LUMC, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: H J M A A
authors.initials: HJ
authors.lastname: Zijlmans
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: H J
authors.initials: HJ
authors.lastname: Baelde
authors.forename: P H C
authors.initials: PH
authors.lastname: Eilers
authors.forename: G G
authors.initials: GG
authors.lastname: Kenter
authors.forename: A
authors.initials: A
authors.lastname: Gorter
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D019656:Loss of Heterozygosity; D008264:Macrophages / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018932:Chemokine CCL2; D012333:RNA, Messenger