High expression of GRP78/BiP as a novel predictor of favorable outcomes in patients with advanced thymic carcinoma

Abstract

Our findings indicate that the overexpression of GRP78/BiP is a novel predictor of favorable outcomes in patients with ATC who receive combination chemotherapy.

Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma

“…Immunohistochemical staining was performed as described previously [20,32,33,34,35] and using the following antibodies: rabbit monoclonal anti-VEGFR2 (1:400; Abcam, Tokyo, Japan); mouse monoclonal anti-STMN1 (1:100; Santa Cruz Biotechnology, Dallas, TX, USA); mouse monoclonal anti-TUBB3 (1:500; MMS-435P; Convance, San Diego, CA, USA); rabbit polyclonal anti-TS (1:1600; clone RTSSA; Taiho Pharmaceutical, Saitama, Japan); rabbit polyclonal anti-Topo-II (1:100; ab180393, Abcam); anti-GRP78/BiP (1:100; Cell Signaling Technology, Danvers, MA, USA). VEGFR2 levels were assessed semi quantitatively by estimating a weighted average of the percentage of tumor cells stained on whole tumor slides (0 = no staining, 1 = positive staining in 1%–10% of the tumor cells, 2 = positive staining in 11%–25% of the tumor cells, 3 = positive staining in 26%–75% of the tumor cells, and 4 = positive staining in >75% of the tumor cells).…”

Expression level of GRP78/BiP as a predictor of favorable or unfavorable outcomes in cancer patients

“…Furthermore, a poor prognosis has been established for patients with high expression of GRP78 in gastric cancer, breast cancer, prostate cancer, and renal cell carcinoma. On the contrary, several studies report favorable prognosis and higher survival for patients upregulating GRP78 in esophageal, colorectal, lung and thymic cancers (13).…”

“…However, while accumulating data are available on the role and mechanisms of action of GRP78 in cancer cells, its value as predictive biomarker for disease evolution and prognosis in different cancers is today still debated and some apparently controversy studies have been recently published (13).…”

“…GRP78 has been correlated with cancer cell survival, tumor growth, metastasis, tumor size, treatment resistance, protective role against lysis by immune cells, high disease clinical stage, cancer recurrence and low survival (13)(14)(15). Furthermore, a poor prognosis has been established for patients with high expression of GRP78 in gastric cancer, breast cancer, prostate cancer, and renal cell carcinoma.…”

“…Another reason that explains the difficulty to obtain homogeneous conclusions is the report of results from different types of cancerous tissues. High GRP78 expression has been shown to be associated with favorable prognosis in esophageal, colorectal, lung and thymic cancers whereas it seems detrimental in gastric, breast, prostate cancer, and renal cancers (13). Moreover, the tumour microenvironment is not homogeneous and presents for example different levels of hypoxia (21).…”