Features of potentially predictive biomarkers of chemotherapeutic efficacy in small cell lung cancer.

Abstract

INTRODUCTION:

One-size-fits-all chemotherapy does not improve survival in patients with small cell lung cancer (SCLC). Excision repair cross-complementing group 1 (ERCC1), ribonucleotide reductase 1 (RRM1), thymidylate synthase (TS), and topoisomerase 2alpha (Topo2alpha) expression levels are predictive of chemotherapeutic efficacy in some malignancies. Our aim was to determine the expression levels of these proteins to assess their potential clinical utility in SCLC.

METHODS:

We used an immunofluorescence-based automated quantitative technique to score RRM1, ERCC1, TS, and Topo2alpha levels in tumor specimens from 100 patients with SCLC and immunohistochemistry to semiquantitatively score levels of TS, 5-phosphoribosyl-glycinamide formyl-transferase, and folyl-polyglutamate synthase expression. Confocal microscopy was used for subcellular localization in SCLC cells.

RESULTS:

RRM1, ERCC1, and Topo2alpha staining was predominantly nuclear and TS mainly cytoplasmic. Using immunohistochemistry, we found that TS (antibody 106) and TS (antibody 4H4) scores were strongly correlated (r = 0.82, p < 0.0001). By automated quantitative technique, RRM1 and Topo2alpha levels were highly correlated (r = 0.56, p < 0.0001). ERCC1 and TS levels had a narrow and low range of expression. There was no correlation between any of these biomarkers and patients' age or sex.

CONCLUSION:

Considering this clinical evidence, expression levels of RRM1 and Topo2alpha may have utility for chemotherapy customization. Clinical validation of their predictive power is desirable in a prospective clinical trial.

• Authors: Alberto A Chiappori, Zhong Zheng, Tingan Chen, Bhupendra Rawal, Michael J Schell, Brian P Mullaney, Gerold Bepler
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 5 Issue 4 Pg. 484-90 (Apr 2010) ISSN: 1556-1380 [Electronic] United States
• PMID: 20107425 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• DNA-Binding Proteins
• Tumor Suppressor Proteins
• RRM1 protein, human
• Ribonucleoside Diphosphate Reductase
• Thymidylate Synthase
• ERCC1 protein, human
• Endonucleases
• DNA Topoisomerases, Type II

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (metabolism)
• Biomarkers, Tumor (metabolism)
• DNA Topoisomerases, Type II (metabolism)
• DNA-Binding Proteins (metabolism)
• Endonucleases (metabolism)
• Female
• Fluorescent Antibody Technique
• Humans
• Immunoenzyme Techniques
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Ribonucleoside Diphosphate Reductase
• Small Cell Lung Carcinoma (drug therapy, metabolism, pathology)
• Survival Rate
• Thymidylate Synthase (metabolism)
• Treatment Outcome
• Tumor Suppressor Proteins (metabolism)