Prognostic impact of the expression of Hedgehog proteins in cervical carcinoma FIGO stages I-IV treated with radiotherapy or chemoradiotherapy
2014 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 135, no 2, 305-311 p.Article in journal (Refereed) Published
Objective: Hedgehog signaling proteins were assessed in patients with cervical carcinoma receiving chemoradiation. Associations between five Hedgehog proteins and prognosis were studied.
Methods: In all, 131 cases of cervical carcinomas (FIGO stages I-IV) were immunohistochemically (IHC) analyzed for Patched (PTCH), Smoothened (SMO), and GLI1, GLI2 and GLI3 protein expression. Associations between Hedgehog protein expressions, clinicopathological factors, and clinical outcome data were examined.
Results: Positive IHC staining for the five Hedgehog proteins was recorded in 8% to 37% of the tumor cells. The highest frequency was noted for SMO and the lowest for all. There was a significant association between low SMO- and GLI2-expression and KRAS-mutation. Tumors with overexpressed SMO had a higher frequency of residual tumor or local recurrences than tumors with low SMO expression. Patients with tumors expressing PTCH in more than 75% of the cells had significantly (P = 0.023) better recurrence-free survival than patients with tumors with low expression. The opposite situation was true for SMO. For GLI2, there was a statistically significant difference with regard to overall (P = 0.004) and distant (P = 0.015) relapse rate for groups with expression of GLI2 in the range of 5-25% compared to higher rates.
Conclusions: A predictive and prognostic value was found for PTCH, SMO, and GLI2 with regard to residual carcinoma, local recurrences, and for GLI2 distant relapses. The Hedgehog signaling pathway also seems to play an important role in cervical carcinogenesis together with HPV16-infection and KRAS-mutation.
Place, publisher, year, edition, pages
Academic Press, 2014. Vol. 135, no 2, 305-311 p.
Cervical carcinoma, Hedgehog proteins, Prognosis
Cancer and Oncology Obstetrics, Gynecology and Reproductive Medicine
IdentifiersURN: urn:nbn:se:oru:diva-56331DOI: 10.1016/j.ygyno.2014.08.026ISI: 000345605200023PubMedID: 25158038ScopusID: 2-s2.0-84914169236OAI: oai:DiVA.org:oru-56331DiVA: diva2:1081655
Research Foundation at the Department of Oncology
Research Funds of the University Hospital, Örebro
Foundation for Research in Gynecological Cancer, Örebro, Sweden 2017-03-142017-03-142017-03-29Bibliographically approved