Correlation among 16 biological factors [p53, p21waf1, MIB-1 (Ki-67), p16INK4A, cyclin D1, E-cadherin, Bcl-2, TNF-α, NF-κB, TGF-β, MMP-7, COX-2, EGFR, HER2/neu, ER, and HIF-1α] and clinical outcomes following curative chemoradiation therapy in 10 patients with esophageal squamous cell carcinoma

Abstract

The expression levels of 16 proteins were analyzed to identify prognostic correlations in esophageal squamous cell carcinoma (ESCC) treated with concurrent chemoradiation therapy (CCRT). The immunohistochemical expression levels of p53, p21waf1, molecular immunology borstel-1 (MIB-1, Ki-67), p16INK4A, cyclin D1, E-cadherin, Bcl-2, tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, transforming growth factor (TGF)-β, matrix metalloproteinase (MMP)-7, cyclooxygenase (COX)-2, epidermal growth factor receptor (EGFR), human EGFR type 2 (HER2/neu), estrogen receptor (ER) and hypoxia-inducible factor (HIF)-1α were studied in 10 cases of ESCC treated with CCRT. The patients underwent CCRT between 2000 and 2010. The mean patient age was 68.1 years (range, 46-80 years). The numbers of patients in stages I, II, III and IV of the disease were 2, 2, 3 and 3, respectively. Of the tumors, 8 were positive for p53, 6 for p21waf1, 7 for MIB-1 (Ki-67), 7 for p16INK4A, 7 for cyclin D1, 8 for E-cadherin, 3 for Bcl-2, 0 for TNF-α, 5 for NF-κB, 7 for TGF-β, 9 for MMP-7, 7 for COX-2, 5 for EGFR, 1 for HER2/neu, 1 for ER and 7 for HIF-1α. The 2-year overall survival rate of patients expressing high levels of MIB-1 was 71% (±17%) compared with 0% (P=0.019) for those expressing low levels. For NF-κB, the rate was 0% for patients with high levels compared with 100% (P<0.018) for those with low levels. The 2-year local control rates of HER2/neu were 0% in patients expressing high levels and 88% (±12%) in patients expressing low levels (P=0.027). The 2-year disease-free survival rates of HER2/neu and ER were 0% for patients expressing high levels compared with 56% (±17%) for those with low levels (P=0.027). There were no significant correlations between the expression levels of the other proteins and clinical outcomes. In the present study, high levels of MIB-1 and low levels of NF-κB, HER2 and ER were shown to be good prognostic factors following definitive CCRT for ESCC.

The human amniotic fluid mesenchymal stem cells therapy on, SKOV3, ovarian cancer cell line

“…Thus, retinoblastoma protein (Rb) remains and E2F factor is not released consequently, cessation of cell cycle occurs (Jackstadt, Jung, & Hermeking, ). In other words, for the inhibition of cell cycle, the expression of P53 and P21 increases (Shibata‑Kobayashi et al, ). Our findings also confirm the apoptosis induction in cancer cells by stem cells causes increase in P21 and P53 gene expressions as found in previous studies.…”

The potential of molecular markers to improve interventions through the natural history of oesophageal squamous cell carcinoma

“…In the attempt to find a wider panel of biomarkers for treatment response in ESCC, a recent study has evaluated the expression level of 16 proteins, including p53, in ESCC treated with CCRT (concurrent chemoradiation therapy) [69]. Although the number of patients included in the study was quite small, the authors showed that high levels of MIB1 (mindbomb E3 ubiquitin protein ligase 1) and low levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells [NF-κB (nuclear factor κB)], HER2 (human epidermal growth factor receptor 2) and ER (oestrogen receptor) are good prognostic factors following definitive CCRT for ESCC.…”

Novel Candidate Biomarkers of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma: A Systematic Review

“…The correlation between a high MIB-1 index and poor prognosis is well known in breast cancer [77]. By contrast, Shibata et al [78] reported that ESCC patients with a higher MIB-1 index showed significantly better OS following definitive CRT than patients with a lower index. It was also reported from a study of 56 ESCC patients that overexpression of MIB-1 is a significant factor for a complete endoscopic response following definitive CRT [79].…”

“…Estrogen promotes tumor cell proliferation by acting via the estrogen receptor, and that proliferation appears to be enhanced in tumor cells overexpressing HER2. Shibata et al [78] also showed that low levels of NF-κB, HER2 and estrogen receptor were good prognostic factors following definitive CCRT.…”