Protein Expression May Predict Response to Radiation Therapy for Head and Neck Patients

Platinum chemotherapy using agents such as cisplatin is an important treatment for squamous cell carcinoma of the head and neck (SCCHN), while chemoradiation is often used for SCCHN patients with high-risk clinical features. Considering the significant morbidity of these treatments, it is important that they are administered only to those patients who are likely to benefit.

The excision repair cross-complementing group 1 (ERCC1) enzyme has an essential role in the pathways used by cancer cells to control damage from cisplatin-based chemotherapy and chemoradiation, and therefore ERCC1+ tumors are more resistant to cisplatin and radiation than ERCC1− cell lines. These roles suggest ERCC1 expression in the nucleus of tumor cells is a potentially valuable predictor of response to chemotherapy and chemoradiation.

To assess ERCC1 protein expression, a team led by Fox Chase medical oncologist Ranee Mehra, MD, used immunofluorescence staining and automatic quantitative analysis on tumors from Fox Chase’s biosample repository. They also analyzed three different antibodies — 8F1, FL297, and HPA029773 — for their ability to detect ERCC1. The results of their research were published in December in Clinical Cancer Research.

For SCCHN associated with traditional risk factors such as tobacco use, the researchers found that low ERCC1 expression was associated with a survival benefit among patients who received adjuvant radiotherapy after surgery. These tumors are known to be less sensitive to chemoradiation, and the association with ERCC1 expression provides a potential explanation for this well-established clinical finding. While it therefore appears useful as a biomarker for response to radiotherapy, ERCC1 expression did not appear to predict survival among patients treated with surgery alone. The latter are usually those with a better prognosis, a factor independent of treatment.

Unexpectedly, the researchers also found that cells taken from recurrent tumors showed lower levels of ERCC1 expression than cells from primary tumors. “The finding that recurrent disease shows lower ERCC1 expression levels… potentially reflects altered DNA  repair capacity in response to prior therapy,” they note, adding that “this warrants study in a larger series.” Both antibodies 8F1  and HPA029773 appeared to be useful for detecting ERCC1 in the cell’s nucleus.

Ranee Mehra, MD

Ranee Mehra, MD

Mehra’s co-authors include Fang Zhu, PhD, Dong-Hua Yang, MD, PhD, Kathy Q. Cai, MD, PhD, JoEllen Weaver, BS, MT, Mahendra K. Singh, PhD, Anna S. Nikonova, PhD, Erica A. Golemis, PhD, Douglas B. Flieder, MD, Harry S. Cooper, MD, Miriam  Lango, MD, John A. Ridge, MD, PhD, FACS, and Barbara Burtness, MD.