Τίτλος:
Prognostic and predictive factors in patients with metastatic or recurrent cervical cancer treated with platinum-based chemotherapy.
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Recognizing resistance or susceptibility to the current standard cisplatin and paclitaxel treatment could improve therapeutic outcomes of metastatic or recurrent cervical cancer. Methods: Forty-five tissue samples from patients participating in a phase II trial of cisplatin and ifosfamide, with or without paclitaxel were collected for retrograde analysis. Immunohistochemistry and genotyping was performed to test ERCC1, III Β-tubulin, COX-2, CD4, CD8 and ERCC1 (C8092A and N118 N) and MDR1 (C3435T and G2677 T) gene polymorphisms, as possible predictive and prognostic markers. Results were statistically analyzed and correlated with patient characteristics and outcomes. Results: Patients with higher levels of ERCC1 expression had shorter PFS and OS than patients with low ERCC1 expression (mPFS:5.1 vs 10.2 months, p = 0.027; mOS:10.5 vs. 21.4 months, p = 0.006). Patients with TT in the site of ERCC1 N118 N and GT in the site of MDR1 G2677 T polymorphisms had significantly longer PFS (p = 0.006 and p = 0.027 respectively). ERCC1 expression and the ERCC1 N118 N polymorphism remained independent predictors of PFS. Interestingly, high III beta tubulin expression was associated with chemotherapy resistance and fewer responses [5/20 (25%)] compared to lower III Β-tubulin expression [15/23 (65.2%)] (p = 0.008). Finally, III Β-tubulin levels and chemotherapy regimen were independent predictors of response to treatment. Conclusions: ERCC1 expression proved to be a significant prognostic factor for survival in our metastatic or recurrent cervical cancer population treated with cisplatin based chemotherapy. ERCC1 N118 N and MDR1 G2677 T polymorphism also proved of prognostic significance for disease progression, while overexpression of III Β-tubulin was positively correlated with chemotherapy resistance. © 2017 The Author(s).
Συγγραφείς:
Karageorgopoulou, S.
Kostakis, I.D.
Gazouli, M.
Markaki, S.
Papadimitriou, M.
Bournakis, E.
Dimopoulos, M.-A.
Papadimitriou, C.A.
Εκδότης:
BioMed Central Ltd.
Λέξεις-κλειδιά:
beta tubulin; CD4 antigen; CD8 antigen; cisplatin; cyclooxygenase 2; excision repair cross complementing protein 1; ifosfamide; multidrug resistance protein 1; paclitaxel; platinum complex; antineoplastic agent; cisplatin; ifosfamide; paclitaxel; tumor marker, adult; aged; Article; cancer combination chemotherapy; cancer growth; cancer prognosis; cancer recurrence; cancer resistance; cancer survival; clinical article; clinical outcome; controlled study; down regulation; drug response; female; gene expression regulation; gene overexpression; genotype; histopathology; human; human cell; human tissue; immunohistochemistry; median survival time; metastasis; overall survival; predictive value; progression free survival; protein expression; single nucleotide polymorphism; survival analysis; survival prediction; tumor associated leukocyte; upregulation; uterine cervix cancer; adenocarcinoma; clinical trial; follow up; genetics; male; middle aged; multicenter study; pathology; phase 2 clinical trial; prognosis; randomized controlled trial; secondary; squamous cell carcinoma; survival rate; tumor recurrence; uterine cervix tumor, Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cisplatin; Female; Follow-Up Studies; Humans; Ifosfamide; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Prognosis; Survival Rate; Uterine Cervical Neoplasms
DOI:
10.1186/s12885-017-3435-x
