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

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Abstract

Background

Prognostic factors aid in the stratification and treatment of cancer. This study evaluated the prognostic significance of human epidermal growth factor receptor (HER) family members (HER1–4) expression in patients with operable pancreatic cancer.

Methods

The expression of individual HER proteins in patient tissue specimens was detected by immunohistochemistry staining. Patient follow-up time was between 1.0 and 78.1 months.

Results

Positive expression of HER1, HER2, HER3 and HER4 was detected in 41.4, 60.0, 24.3 and 65.7% of cases, respectively. Kaplan–Meier analysis revealed that HER3 positive expression was associated with decreased median survival time (12.0 vs. 25.6 months for HER3 positive and negative groups, respectively; P = 0.013). Cox’s regression confirmed that positive HER3 expression was an independent predictor of poor survival (RR = 3.684, P = 0.001). In contrast, HER4 negative patients had a significantly decreased median survival time when compared with HER4 positive patients (11.4 vs. 25.6 months, respectively; P = 0.027). However, HER4 was not an independent predictor of survival. No significant association between HER1 or HER2 expression and survival was observed ( P = 0.626 & P = 0.859, respectively).

Conclusions

HER3 is an independent prognostic marker for patients with operable pancreatic cancer. HER4 may also be of potential prognostic value in this disease and deserves further attention.

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Most cited references 25

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KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab.

Astrid Lièvre, Jean-Baptiste Bachet, Valérie Boige … (2008)

Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival. Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed. A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively. These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.

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Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators.

T Sohn, Darren Yeo, J L Cameron … (2015)

This large-volume, single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head, neck, uncinate process, body, or tail of the pancreas. Between January 1984 and July 1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Both univariate and multivariate models were used to determine the factors influencing survival. Of the 616 patients, 526 (85%) underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy for adenocarcinoma extensively involving the gland. The mean age of the patients was 64.3 years, with 54% being male and 91% being white. The overall perioperative mortality rate was 2.3%, whereas the incidence of postoperative complications was 30%. The median postoperative length of stay was 11 days. The mean tumor diameter was 3.2 cm, with 72% of patients having positive lymph nodes, 30% having positive resection margins, and 36% having poorly differentiated tumors. Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors (4.7 vs. 3.1 cm, P < 0.0001), but fewer node-positive resections (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P < 0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5 years, with a median survival of 17 months. For right-sided lesions the 1- and 5-year survival rates were 64% and 17%, respectively, compared to 50% and 15% for left-sided lesions. Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins (hazard ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02), well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005), and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P < 0.0001). Tumor location in head, neck, or uncinate process approached significance in the final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas. Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators. Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status.

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HER3 overexpression and survival in solid tumors: a meta-analysis.

Alberto Ocana, Francisco Vera-Badillo, Bostjan Seruga … (2013)

The human epidermal growth factor receptor 3 (HER3) is an ErbB/HER family member that dimerizes with other ErbB receptors such as HER2. Numerous agents against HER3 are in clinical development despite variable data for the prognostic impact of HER3 expression. Here we report a meta-analysis of the association of HER3 expression and survival in solid tumors. PubMed was searched for studies evaluating expression of HER3 (as measured by immunohistochemistry) and overall survival (OS) in solid tumors. Published data were extracted and computed into odds ratios (ORs) for death at 3 and 5 years. Data were pooled using the Mantel-Haenszel random-effect model. All statistical tests were two-sided. Analysis included 12 studies: three that evaluated colorectal cancer, two that evaluated gastric cancer, two that evaluated breast cancer, and one each that evaluated melanoma, ovarian cancer, head and neck cancer, pancreatic cancer, and cervical cancer. The median percentage of cancers with HER3 overexpression was 42.2%. HER3 was associated with worse OS at both 3 years (OR = 2.24, 95% confidence interval [CI] = 1.77 to 2.83, P < .001) and 5 years (OR = 2.20, 95% CI = 1.75 to 2.76, P < .001). Among studies with common HER2 overexpression (breast, gastric, and ovarian cancers), the magnitude of effect of HER3 on OS was statistically significantly greater for both 3-year OS (OR = 3.12, 95% CI = 2.24 to 4.37) and 5-year OS (OR = 2.84, 95% CI = 2.09 to 3.88). Expression of HER3 is associated with worse survival in solid tumors. The influence of HER3 may be greater in those tumors where HER2 is commonly overexpressed.

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Author and article information

Contributors

Qin Li: qinli128003@163.com

Lei Zhang: 245468932@qq.com

XiuHong Li: 13811879213@163.com

Han Yan: Yanhanzi112@sina.com

Liuting Yang: 641253427@qq.com

Yingying Li: lyyxfyy@163.com

Teng Li: Lixiaochouteng@163.com

Jing Wang: Wangjing81@189.cn

Bangwei Cao: +86 10 63138655 , oncology@ccmu.edu.cn

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 21 November 2016

Publication date PMC-release: 21 November 2016

Publication date Collection: 2016

Volume: 16

Electronic Location Identifier: 910

Affiliations

[1 ]Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050 China

[2 ]Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

[3 ]Research Experiments Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China

[4 ]Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan, China

[5 ]Department of Pathology and Pathophysiology, Basic Medical College, Capital Medical University, Beijing, China

[6 ]Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China

Article

Publisher ID: 2889

DOI: 10.1186/s12885-016-2889-6

PMC ID: 5117489

PubMed ID: 27871278

SO-VID: d92bc6a6-0bf8-42eb-82c3-a4854fb0c00c

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 4 June 2016

Date accepted : 25 October 2016

Funding

Funded by: National Natural Science Foundation of China (CN)

Award ID: 81301912 and 81272615

Funded by: Beijing Municipal Health System High-level Health Person Foundation Project

Award ID: 2014-3-005

Funded by: Beijing Municipal Science and Technology Commission

Award ID: 2016-2018

Award Recipient : Qin Li

Funded by: the Capital Health Research and Development Project

Award ID: 2016-2018

Award Recipient : Jing Wang

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: pancreatic cancer,prognosis,her1,her2,her3

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: pancreatic cancer, prognosis, her1, her2, her3

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The prognostic significance of human epidermal growth factor receptor family protein expression in operable pancreatic cancer : HER1–4 protein expression and prognosis in pancreatic cancer

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Abstract

Background

Methods

Results

Conclusions

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Karger: Oncology

Most cited references 25

KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab.

Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators.

HER3 overexpression and survival in solid tumors: a meta-analysis.

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