ABSTRACT
INTRODUCTION: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. MATERIAL AND METHODS: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan-Meier method and log-rank test. RESULTS: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27-96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p < 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p < 0.0001; p < 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα-) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616-11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073-37.693; p < 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. CONCLUSION: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.
ABSTRACT
OBJECTIVE: Mesenteric ischemia (MESI) is a rare but often fatal complication in patients after cardiac surgery. Non-specific clinical symptoms and lack of specific laboratory parameters complicate the diagnosis. We evaluated potential serum markers for MESI in cardiac surgery patients. METHODS: Between March and October 2012, serial serum samples of 567 elective cardiac surgery patients were collected 1, 24, and 48 h after the operation, and concentrations of potential markers for MESI [α-glutathione-S-transferase (αGST), intestinal fatty-acid-binding protein (iFABP), and D-lactate] were measured retrospectively. In patients requiring laparotomy, blood samples obtained 72, 48, 24, and 12 h before the laparotomy were additionally measured and compared to all other patients (control group). RESULTS: Laparotomy was performed in 18 patients at 11±7 days after cardiac surgery. MESI was found in 9/18 patients. Already 1 h after cardiac surgery, the serum concentrations of D-lactate (37±18 vs. 25±20 nmol/mL, p<0.01) and αGST (82±126 vs. 727±1382 µg/L, p<0.01) in patients undergoing laparotomy were increased compared to the control group. Between patients with and without MESI, differences were only found for iFABP 24 h after cardiac surgery (1.1±0.4 vs. 2.9±0.6 ng/mL, p=0.04) and up to 72 h before laparotomy (0.56±0.72 vs. 2.51±1.96 ng/mL, p=0.01). CONCLUSIONS: D-lactate and αGST were early markers for gastrointestinal complications after cardiac surgery. Before laparotomy, lowered iFABP levels indicated MESI. Routinely used, these markers can help identify patients with gastrointestinal complications after cardiac surgery early, and might be useful for the evaluation of new therapeutic or preventive strategies.
