Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma

Abstract

Abstract. Esophageal squamous cell carcinoma (ESCC)is the eighth most frequent neoplasm in China. However, the expression levels of human epidermal growth factor receptor 2 (HER2) and multidrug resistance protein 1 (MRP1) in patients with ESCC remain to be determined. In the present study, 829 ESCC cases were evaluated using immunohistochemistry. The association between the expression levels of HER2 and MRP1 and the patient's clinicopathological factors was analyzed using Fisher's exact test or χ 2 test. Univariate analysis was performed via Kaplan-Meier survival curves, while the Cox proportional hazard model was used for multivariate analysis. A significant correlation was observed between the expression levels of HER2 and the patient's gender (P<0.050), tumor size (P=0.013) and venous/lymphatic invasion (P= 0.039). However, no significant correlation was identified between the expression levels of MRP1 and the clinicopathological factors of the patients. In univariate analysis, gender, differentiation, depth of invasion, clinical stage, adjuvant radiotherapy or chemotherapy and lymph node metastasis were significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients with ESCC (P<0.050). The graphical representation of the Kaplan-Meier estimate curves suggested that the expression levels of HER2 or MRP1 did not exert any influence on prognosis (log-rank test, P>0.050). In multivariate analysis, tumor location, gender, clinical stage, differentiation and lymph node metastasis were identified as independent factors of prognosis in patients with ESCC (P<0.050). However, the expression levels of HER2 or MRP1 were not independently associated with PFS or OS in these patients. In conclusion, the present large-scale study demonstrates that the protein expression levels of HER2 and MRP1 does not exert any influence on the prognosis of ESCC.

ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

“…High ABCC1 protein expression in pre-treatment tumor biopsies significantly correlated with poor response of EAC patients ( n = 40) to 5-fluorouracil- and cisplatin-based neoadjuvant therapy, while ABCB1 expression had no predictive value in the later study [ 32 ]. However, largest study to date failed to observe any prognostic association for immunohistochemically detected ABCC1 protein expression in tumors from ESCC patients ( n = 829) [ 41 ]. Most recently, correlation of ABCC1 and ABCB1 protein expression with that of Caveolin-1 ( CAV1 , 601047) in tumor tissues from ESCC patients ( n = 84) has been observed and CAV1 expression knockdown also decreased transcript levels of both transporters in ECA-109 cell line in vitro [ 151 ], suggesting a potential interplay between membrane proteins with different functions and their putative use as therapeutic targets.…”

“…Most recently, correlation of ABCC1 and ABCB1 protein expression with that of Caveolin-1 ( CAV1 , 601047) in tumor tissues from ESCC patients ( n = 84) has been observed and CAV1 expression knockdown also decreased transcript levels of both transporters in ECA-109 cell line in vitro [ 151 ], suggesting a potential interplay between membrane proteins with different functions and their putative use as therapeutic targets. In summary, although predictive value of ABCC1 protein expression has been suggested, studies aiming at its prognostic role failed [ 40 , 41 ] and, therefore, other members of the C family and perhaps combinations of more transporters should be followed in the future.…”

MicroRNA‐153‐3p regulates cell proliferation and cisplatin resistance via Nrf‐2 in esophageal squamous cell carcinoma

“…However, an increasing number of studies have shown tumor cell resistance to cisplatin, both in vivo and in vitro . This is one of the major factors contributing to treatment failure in ESCC patients . MicroRNAs (miRNAs) are endogenous, small non‐coding RNAs that play an essential role in the regulation of gene expression and tumor progression; in addition, these have been linked to chemotherapy resistance .…”

“…17,18 This is one of the major factors contributing to treatment failure in ESCC patients. 19,20 MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that play an essential role in the regulation of gene expression and tumor progression; in addition, these have been linked to chemotherapy resistance. 21 Many studies have suggested that miR-153 is a tumor suppressor miRNA.…”

HER2 expression and relevant clinicopathological features in esophageal squamous cell carcinoma in a Chinese population

“…The relationship between HER2 IHC expression and the clinicopathologic characteristics of patients with ESCC is controversial based on data from previous studies. Chen et al reported that HER2 IHC expression levels were associated with gender, tumor size, venous/ lymphatic invasion and HER2 positivity rate was higher in female than in male ESCC patients [19]. In contrast, Gonzaga et al and Sato-Kuwabara et al revealed that there was no correlation between HER2 IHC expression and clinicopathological parameters [2,7].…”