title: Survivin protein as predictor of pathologic response in patients with locally advanced cervical cancer treated with chemoradiation followed by radical surgery.
abstract: We investigated the correlation of pathologic response and immunohistochemically assessed expression of survivin protein in 71 patients with locally advanced cervical cancer treated with chemoradiation (CT/RT) followed by radical surgery. The prognostic role of survivin expression was also evaluated. Immunohistochemical analysis of survivin expression was carried out using the polyclonal rabbit antisurvivin antibody. Cytoplasmic survivin immunoreaction was observed in 69 (97.2%) of 71 cases and nuclear staining in 7 (9.8%) of 71 women. Median cytoplasmic survivin expression was 160 (range, 0-280), and higher levels were observed in patients with residual disease (≥3 mm) in the cervix (survivin level, 160 versus 120; P = .016) and in women with metastatic lymph nodes (survivin levels, 160 versus 150; P = .032). No differences were documented in the distribution of patients with positive nuclear staining, according to clinicopathological variables. In multivariate analysis, cytoplasmic survivin expression emerged as an independent predictor of residual cervical disease and lymph node status after CT/RT. During a follow-up period of 83 months (range, 8-175 months), recurrences occurred in 24 (33.8%) women, and all patients died of disease. Women with high cytoplasmic survivin experienced shorter disease-free survival compared with patients with low levels (5-year disease-free survival, 80.8% versus 55.3%; P = .033). Only a trend was observed for greater overall survival in patients with high expression (5-year overall survival, 81.0% versus 55.3%; P = .069). No survival differences were documented for nuclear survivin status. The immunohistochemically assessed survivin cytoplasmic levels at diagnosis represent a reliable and easily assessable tool to predict response to CT/RT in patients with locally advanced cervical cancer.
authors.affiliation: Department of Pathology, Catholic University of the Sacred Heart, 00168, Rome, Italy. Electronic address: gfzannoni@rm.unicatt.it.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Zannoni
authors.affiliation: Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, Catholic University, 00168, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Petrillo
authors.affiliation: Department of Pathology, University of Genova, 16038, Genova, Italy.
authors.forename: Valerio Gaetano
authors.initials: VG
authors.lastname: Vellone
authors.affiliation: Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, Catholic University, 00168, Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Martinelli
authors.affiliation: Department of Pathology, Catholic University of the Sacred Heart, 00168, Rome, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Chiarello
authors.affiliation: Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, Catholic University, 00168, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.affiliation: Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, Catholic University, 00168, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
mesh_terms: D000328:Adult; D000818:Animals; D059248:Chemoradiotherapy; D003593:Cytoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D011379:Prognosis; D011817:Rabbits; D000077022:Survivin; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin
keywords: Chemoradiation; Locally advanced cervical cancer; Pathologic response; Poor prognosis; Survivin expression