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« Back to Contents CERVICAL CANCER

LiFE re

Literature for ENYGO

Pathology of cervical cancer

Editor Borja Otero prognosis; DR5 nuclear positive tumours have enhanced response to
radiotherapy; and TRAIL as well as caspase-8 loss may be associa-
Descriptive summary ted with malignant progression [15].

ICC development Eukaryotic initiation factor 5A2 (EIF5A2) plays an important role
in tumour progression and its high expression is an independent
HPV 16 and 18 are more frequent in women aged 30-39 compared prognostic factor for overall survival and disease-free survival [16].
to women ≥ 70 [1] and are the most prevalent genotypes in ICC
specimens in different countries [2-6]. ICC treatment outcome

HPV infection needs some cofactors for ICC development such as Low Ku86 and XRCC4 expression, two markers of non-homologous
an inflammatory microenvironment and hypoxia. The way these end joining of DNA, a mechanism to repair DNA double-strand
two mechanisms develop in ICC has been studied in two recent breaks induced by ionizing radiation, is a significant predictor of a
studies. Urokinase plasminogen activator receptor (uPAR) facilitates pathological complete response to radiotherapy [17].
hypoxia-mediated invasion through HIF-1. uPAR expression has
been detected in cervical cancer but not in normal cervix or cervical Tumour G-CSF expression is an indicator of an extremely poor
intraepithelial neoplasia (CIN) by immunohistopathological staining. prognosis in cervical cancer patients treated with chemotherapy.
Regarding the inflammatory microenvironment, fibroblasts support It seems that G-CSF-increases myeloid-derived suppressor cells
Th17 (T helper 17) cell infiltration and maintain chronic inflammation (MDSC), which are involved in the development of chemoresistance.
within high-grade cervical lesions further promoting cancer progre- Moreover, the depletion of MDSC via splenectomy or the administra-
ssion [7,8]. tion of anti-Gr-1 antibody sensitised G-CSF producing cervical cancer
to cisplatin [18].
Finally, some individual characteristics such as CDKN1A and Inter-
leukin-27 genetic polymorphisms might influence the development Novel therapeutic approaches
of ICC, giving some clues about the differences in interindividual
progression of same HPV serotypes infections [9,10]. Prostate-specific membrane antigen-targeted therapy is a promising
treatment of advanced carcinomas. One study has demonstrated
ICC diagnosis that some ICC overexpress this protein, thus being candidates to
receive this treatment [19].
When several cervical biopsies are performed during a colposcopy,
CADM1/MAL methylation hyperexpression seems to be repre- BORIS sf6 is differentially expressed in cervical cancer stem-like
sentative of the worst underlying lesion, particularly for CIN3 and cells and cancer-initiating cells, which are resistant to conventional
cervical cancer. [12] This means that the degree of methylation in the radiotherapy and chemotherapy. These cells have been shown to
CADM1/MAL genes can not only indicate how long an HPV infection be a target for specific cytotoxic T cells turning into candidates for
has been present but also how severe the lesions produced by that immunotherapy [20].
infection are.

ICC prognosis

DNA methylation is an important epigenetic modification frequently
altered in cancer and metabolites associated to this mechanism cou-
ld be markers for ICC prognosis. Levels of 5-hydroxymethylcytosine
have shown differential patterns between ICC and normal cervical
tissues being an independent prognostic factor for both disease-free
and overall survival [14].

TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in
cancer cells. Several TRAIL signalling members have been evaluated
in ICC, showing that high c-FLIP expression is associated to poor

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International Journal of Gynecological Cancer, Volume 26, Supplement #1 Page 36