HER3 Overexpression as an Independent Indicator of Poor Prognosis for Patients with Curatively Resected Pancreatic Cancer

Abstract

Objective: The association between human epidermal growth factor receptor 3 (HER3) overexpression and survival in patients with curatively resected pancreatic cancer was investigated. Methods: Tissue samples from 126 pancreatic cancers without hematogenous or peritoneal metastases recovered from macroscopically curative resection were fixed with formalin, embedded in paraffin and subjected to immunohistochemical staining. Semiquantitative scores of zero (no staining or staining in less than 10% of cancer cells), 1+, 2+, or 3+ were assigned to each sample based on the intensity of staining. Scores of 2+ or 3+ were defined as HER3-positive staining, i.e., HER3 overexpression. Results: HER3 overexpression was observed in 52 of the 126 tissue samples (41.3%). There were no associations between HER3 overexpression and clinicopathological factors, including tumor location, tumor size, tumor differentiation, T/N categories according to the International Union against Cancer, and serum carbohydrate antibody 19-9 level (CA19-9). Univariate analysis demonstrated the median survival time of patients with HER3 overexpression was 37.2 months, while that of patients with HER3-negative samples was 58.6 months (p = 0.008). HER3 overexpression, lymph node metastasis, and elevated serum CA19-9 level were independent predictors of poor prognosis based on multivariate survival analysis. Conclusion: A new prognostic predictor, HER3 overexpression, was identified for resected pancreatic cancer.

Elevated serum CA19-9 level is a promising predictor for poor prognosis in patients with resectable pancreatic ductal adenocarcinoma: a pilot study

“…Ferrone et al [20] reported that the preoperative level of CA19-9 was not an independent prognostic factor in patients with resectable pancreatic adenocarcinoma. However, a contradictory result has been revealed by the Waraya [10], Hartwig [22], and Hirakawa [15] groups, arguing that the preoperative CA19-9 level is an independent prognostic factor on multivariate analysis. The result from our study is consistent with the latter findings.…”

“…Waraya et al [10] and Hirakawa et al [15] reported that a level of CA19-9 >37 was the independent prognostic factor. Berger et al [7] reported that undetectable preoperative CA19-9 levels and a value of CA19-9 >200 U/mL were related to survival.…”

“…However, the cutoff value of CA19-9 used to predict prognosis varied among these reports. A value of 37 U/mL has been frequently used as the cutoff value in previous studies [7,10,14,15]. The normal physiological level of serum CA19-9 is defined as under 37 U/mL, which was estimated based on the standard deviation of the distribution of serum CA19-9 levels among normal persons.…”

89Zr-Lumretuzumab PET Imaging before and during HER3 Antibody Lumretuzumab Treatment in Patients with Solid Tumors

“…HER3 is physiologically expressed in normal human tissues, such as the gastrointestinal, urinary, respiratory and reproductive tract and skin (2). In multiple cancer types, HER3 overexpression has been linked with poor prognosis which increased interest in HER3 as potential target in cancer therapy (3)(4)(5)(6)(7)(8)(9).…”

The prognostic significance of human epidermal growth factor receptor family protein expression in operable pancreatic cancer

“…HER protein staining was scored as either 0, 1+, 2+, or 3+, the cytoplasm and membrane-staining intensity and pattern were evaluated according to the following scale [20]: no staining is observed or is observed in less than 10% of the tumor cells (score 0), weak staining is detected in 10% or more tumor cells (score 1+), moderate staining is observed in 10% or more tumor cells (score 2+) and strong staining is observed in 10% or more tumor cells (score 3). Scores of 0, 1+ and 2+ were taken to represent negative protein expression, while a score of was 3+ was taken to represent positive protein expression.…”