GRP78 protein expression as prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer

Purpose We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer. Materials and Methods All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5- fluorouracil (400 mg/m²/day) and leucovorin (20 mg/m²/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies. Expression of GRP78 and Cripto-1 proteins was determined by immunohistochemistry and was assessed in 101 patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Results High expression of GRP78 and Cripto-1 proteins was observed in 86 patients (85.1%) and 49 patients (48.5%), respectively. Low expression of GRP78 protein was associated with a significantly high rate of down staging (80.0% vs. 52.3%, respectively; p = 0.046) and a significantly low rate of recurrence (0% vs. 33.7%, respectively; p = 0.008) compared with high expression of GRP78 protein. Mean recurrence-free survival according to GRP78 expression could not be estimated because the low expression group did not develop recurrence events but showed a significant correlation with time to recurrence, based on the log rank method (p = 0.007). GRP78 also showed correlation with overall survival, based on the log rank method (p = 0.045). Conclusion GRP78 expression is a predictive and prognostic factor for down staging, recurrence, and survival in rectal cancer patients treated with 5-fluorouracil and leucovorin neoadjuvant CRT.