Elsevier

Radiotherapy and Oncology

Volume 97, Issue 2, November 2010, Pages 352-359
Radiotherapy and Oncology

Clinical radiobiology
Low ERCC1 mRNA and protein expression are associated with worse survival in cervical cancer patients treated with radiation alone

https://doi.org/10.1016/j.radonc.2010.08.019Get rights and content

Abstract

Purpose

To evaluate the association of excision repair cross-complementation group 1 (ERCC1) expression, using both mRNA and protein expression analysis, with clinical outcome in cervical cancer patients treated with radical radiation therapy (RT).

Experimental design

Patients (n = 186) with locally advanced cervical cancer, treated with radical RT alone from a single institution were evaluated. Pre-treatment FFPE biopsy specimens were retrieved from 112 patients. ERCC1 mRNA level was determined by real-time PCR, and ERCC1 protein expression (FL297, 8F1) was measured using quantitative immunohistochemistry (AQUA®). The association of ERCC1 status with local response, 10-year disease-free (DFS) and overall survival (OS) was analyzed.

Results

ERCC1 protein expression levels using both FL297 and 8F1 antibodies were determined for 112 patients; mRNA analysis was additionally performed in 32 patients. Clinical and outcome factors were comparable between the training and validation sets. Low ERCC1 mRNA expression status was associated with worse OS (17.9% vs 50.1%, p = 0.046). ERCC1 protein expression using the FL297 antibody, but not the 8F1 antibody, was significantly associated with both OS (p = 0.002) and DFS (p = 0.010). After adjusting for pre-treatment hemoglobin in a multivariate analysis, ERCC1 FL297 expression status remained statistically significant for OS [HR 1.9 (1.1–3.3), p = 0.031].

Conclusions

Pre-treatment tumoral ERCC1 mRNA and protein expression, using the FL297 antibody, are predictive factors for survival in cervical cancer patients treated with RT, with ERCC1 FL297 expression independently associated with survival. These results identify a subset of patients who may derive the greatest benefit from the addition of cisplatin chemotherapy.

Section snippets

Patients, treatment, and biosamples

One hundred and eighty-six patients who completed radical RT alone, with curative intent, for cervical cancer between 1986 and 1996 at a single institution (Tom Baker Cancer Centre, Calgary, AB) were identified from the Alberta Cancer Registry database. None of the patients were treated with primary surgery or with concurrent chemotherapy. Patients were excluded if they had prior definitive treatment for cervical cancer, active malignancy at another site, and/or less than five years of

Results

Of the 186 patients identified from the database, 112 had pre-treatment FFPE tumor biopsy specimens available for the analysis for evaluation of ERCC1 by AQUA® technology, using both FL297 and 8F1 antibodies. Of these 112 FFPE biopsy specimens, 63 (56%) were of sufficient size (at least 1 cm) and tumor density (at least 50% tumor) to be additionally selected for mRNA expression analysis. ERCC1 mRNA expression levels were successfully measured from 32 of these specimens. ERCC1 mRNA levels could

Discussion

In the present study, we found that low ERCC1 mRNA and protein expression are associated with worse survival in cervical cancers treated with radiation therapy, with ERCC1 expression measured using the FL297 antibody independently associated with OS on multivariate analysis. This is the largest study of ERCC1 in cervical cancer where the expression was comprehensively measured using multiple assay methods. At first glance, these findings seem surprising given the pre-clinical evidence

Financial support

Funded in part by the Alberta Cancer Foundation and the Southern Alberta Cancer Research Institute.

Conflict of interest statement

None of the authors (C.D., M.P., M.E., A.K., S.P., P.C., D.H., R.D., S.L.-M., and A.M.) have financial and personal relationships with other people or organizations that could inappropriately influence their work.

Acknowledgement

The authors would like to acknowledge the contribution of Ms. Mie Konno for collecting the data used in this study, and Dr. R. Wood for his helpful discussions.

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