BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy.

Abstract

OBJECTIVES:

To investigate whether BCL-2 expression would improve MVP/IGF-1R prediction of clinical outcome in cervix carcinoma patients treated by radiochemotherapy, and suggest possible mechanisms behind this effect.

METHODS:

Fifty consecutive patients, who achieved complete response to treatment, from a whole series of 60 cases suffering from non-metastatic localized cervical carcinoma, were prospectively included in this study from July 1999 to December 2003. Follow-up was closed in January 2011. All patients received pelvic radiation (45-64.80 Gy in 1.8-2 Gy fractions) with concomitant cisplatin at 40 mg/m2/week doses followed by brachytherapy. Oncoprotein expression was studied by immunohistochemistry in paraffin-embedded tumour tissue.

RESULTS:

No relation was found between BCL-2 and clinicopathological variables. High MVP/IGF-1R/BCL-2 tumour expression was strongly related to poor local and regional disease-free survival (P<0.0001), distant disease-free survival (P=0.010), disease-free survival (P<0.0001), and cause-specific survival (P<0.0001). NHEJ repair protein Ku70/80 expression was significantly repressed in tumours overexpressing all three oncoproteins (P=0.047). No differences were observed in proliferation (Ki67 expression) or P53 alteration.

CONCLUSIONS:

BCL-2, MVP, and IGF-1R overexpression were related to poorer clinical outcome in cervical cancer patients who achieved clinical complete response to radiochemotherapy. The NHEJ repair protein Ku70/80 expression could be involved in the regulation of these oncoproteins.

• Authors: Luis Alberto Henríquez-Hernández, Marta Lloret, Beatriz Pinar, Elisa Bordón, Agustín Rey, Amina Lubrano, Pedro Carlos Lara
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 122 Issue 3 Pg. 585-9 (Sep 2011) ISSN: 1095-6859 [Electronic] United States
• PMID: 21708403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Nuclear
• DNA-Binding Proteins
• Ki-67 Antigen
• Proto-Oncogene Proteins c-bcl-2
• TP53 protein, human
• Tumor Suppressor Protein p53
• Vault Ribonucleoprotein Particles
• major vault protein
• Receptor, IGF Type 1
• Xrcc6 protein, human
• Ku Autoantigen

Topics

• Adult
• Aged
• Antigens, Nuclear (biosynthesis)
• DNA-Binding Proteins (biosynthesis)
• Female
• Humans
• Immunohistochemistry
• Ki-67 Antigen (biosynthesis)
• Ku Autoantigen
• Middle Aged
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Receptor, IGF Type 1 (biosynthesis)
• Treatment Outcome
• Tumor Suppressor Protein p53 (biosynthesis)
• Uterine Cervical Neoplasms (drug therapy, metabolism, radiotherapy, therapy)
• Vault Ribonucleoprotein Particles (biosynthesis)