In our study we performed a comprehensive analysis of the prognostic value of HER1C4 in patients with operable pancreatic cancer. receptor, tissue specimens were assigned a score according to the cytoplasm and membrane-staining intensity. Analysis of intensity scores revealed that HER1, HER2, HER3 and HER4 exhibited positive staining in 41.4, 60.0, 24.3 and 65.7% of cases, respectively. Representative images of A-804598 immunostaining related to HER1, 2, 3 & 4 expression in pancreatic cancer tissues are shown in Fig.?2. Open in a separate window Fig. 2 Representative images of HER1C4 tissue staining for all expression scores (0C3+) which were assigned according to the cytoplasm and membrane-staining intensity (original magnification 200) Analysis of the relationship between patient characteristics and median survival time in operable pancreatic cancer The relationship between the clinical/pathological characteristics and median survival time in patients with operable pancreatic cancer are showed in Table?1. Differences in median survival times (MSTs) between subgroups were evaluated using the log-rank test. The MSTs of patients with stump cancer, low differentiation, adenocarcinoma, N1 stage, and CA 19-9 >1200U/ml were significantly lower than those of patients from the corresponding control subgroups (4.87 vs. 17.69?months, valuevalue (for median survival time)value
HER1 positive vs. negative0.5980.281C1.2710.181HER2 positive vs. negative0.9090.420C1.9680.809HER3 positive vs. negative3.6841.732C7.8340.001HER4 positive vs. negative0.8000.375C1.7100.565Stump cancer yes vs. no10.1102.725C37.5060.001Histopathology type
?Adenocarcinoma vs. non-adenocarcinoma4.5951.371C15.4040.013Differentiation poor vs. well3.8041.480C9.7740.006N stage N1 vs. N00.6610.259C1.6850.386The positive lymph node number1.3310.964C1.8380.083CA199 >1200 U/ml vs. <1200 U/ml1.9610.806C4.7700.138 Open in a separate window Discussion There are relatively few studies on the prognostic significance of HER family members in patients with operable pancreatic cancer. To date, the findings regarding the prognostic significance of HER family protein expression in pancreatic cancer have been inconsistent. This may be a consequence of inter-study differences in tissue preparation, the detection antibodies used, and different methods of scoring. In our study we performed a comprehensive analysis of the prognostic value of HER1C4 in patients with operable pancreatic cancer. KaplanCMeier analysis showed that the MST of the HER3 positive group was 12.0?months, which was significantly lower than 25.6?months observed for the HER3 negative group (P?=?0.013). Coxs multiple regression analysis demonstrated that HER3 was an independent predictor of poor prognosis; risk of death associated with HER3 positive expression was 3.684 times greater than that associated with HER3 negative expression (P?=?0.001). Although Coxs multiple regression analysis did not identify HER4 positive expression as an independent predictor of survival, KaplanCMeier analysis did show that the MST of the HER4 positive group was 25.6?months, which was significantly higher than 11.4?months for the HER4 negative group (P?=?0.027). This suggests that HER4 may be of some potential prognostic value in pancreatic cancer and this deserves further attention. No significant association between HER1 or HER2 positive expression and survival were observed, and neither receptor was a predictor of survival. HER1 is overexpressed in a variety of human malignancies [21, 22]. The frequency of HER1 expression in pancreatic cancer has been reported as 30.4%  and 45.1%  in two previous studies. A-804598 In our study HER1 expression was observed in 41.4% of patients. HER1 overexpression has previously been associated with decreased survival [23, 24], and the cumulative 1-, 3- and 5-year survival rates were 48, 20 and 18%, respectively . A previous meta-analysis has shown that three trials reported a survival disadvantage for patients with HER1 expression, while other five trials reported no significant difference, however, the combined hazard ratio was 1.225 (P?=?0.035) . Another meta-analysis drew the opposite conclusion that HER1 was not a significant prognostic factor in resected pancreatic cancer (HR?=?1.35, 95% CI 0.80C2.27, P?>?0.05) . From our analysis, we also drew the conclusion that positive HER1 expression has no prognostic value in operable pancreatic cancer. HER2 expression is associated with decreased disease-specific survival and poor prognosis in patients with breast cancer and gastric cancer [17, 18, 27]. The frequency of HER2 expression and its association with survival in pancreatic cancer remains unclear. Te Velde et al. reported that neither membranous overexpression nor gene amplification of HER2 was seen in pancreatic cancer . A study by Aumayr, et al. observed positive HER2 expression, as determined by IHC staining, in 10% of pancreatic cancer cases, and of these, 7% demonstrated HER2 gene amplification . In our study A-804598 we observed positive HER2 expression in 60.0% of cases, which is significantly higher than that observed by others. Komoto et al. reported that patients with HER2 overexpression had significantly shorter survival times than MAP2K2 those with normal HER2 expression (14.7 vs. 20.7?months, P?=?0.008),.