Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

Purpose

To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy.

Methods and Materials

We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively.

Results

The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively.

Conclusion

Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

Introduction

Currently, radiation therapy (RT) plays an important role in treating cervical cancer. The primary goal of radiation oncologists is to obtain good local control of cervical cancer because successful salvage treatment for local recurrence (LR) after RT is difficult. For patients with non-locally advanced cervical cancer at a high risk for LR, when surgical treatment is considered, local control and survival may be better than with RT alone. Therefore, identifying factors associated with LR may be helpful for improving the treatment outcome of these patients. We first noted that pretreatment carcinoembryonic antigen (CEA) levels in the serum can predict LR in patients with cervical cancer (1); however, clinicopathologic studies on radioresistant cervical cancer have had wide-ranging results 2, 3, 4. Therefore, other molecular markers for the prediction of LR are worth investigating.

The most well-known clinical factor for radioresistant cervical cancer is tumor hypoxia 5, 6. Low hemoglobin (Hb) levels are associated with hypoxia 7, 8, and a lower pretreatment Hb level is associated with LR 9, 10. Furthermore, hypoxia-inducible factor 1α (HIF-1α) is correlated with Hb levels 11, 12. Another molecule involved in radioresistance is H-ras 13, 14, 15. The transcriptional activation of H-ras during the oncogenesis of cervical cancer has been observed in previous studies (16). However, Lee et al (17) reported no prognostic role of the H-ras mutation for survival.

Galectin-1 is a galactose-binding protein regulated by hypoxia 18, 19 and is a prognostic marker for patients with head-and-neck squamous cell carcinoma (20). Interestingly, galectin-1 interacts with H-ras and enhances H-ras activation 21, 22, and H-ras may induce HIF-1α (23) to regulate galectin-1 expression 19, 24. We also identified galectin-1 as a radioresistant marker of cervical cancer cells through its interaction with H-ras (25). Therefore, galectin-1 is considered to be a radioresistant marker, and clinicopathologic studies are needed to validate this hypothesis.