HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series

Aprile, Giuseppe; Maglio, Giovanna De; Menis, Jessica; Casagrande, Mariaelena; Tuniz, Francesco; Pisa, Federica Edith; Fontanella, Caterina; Škrap, Miran; Beltrami, Carlo Alberto; Fasola, Gianpiero; Pizzolitto, Stefano

doi:10.3390/ijms14022370

Cited by 14 publications

(18 citation statements)

References 58 publications

(70 reference statements)

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“…As demonstrated in our preliminary studies [ 23 ], high HER-2 expression was found mainly in primary tumors in rectal cancer patients ( n = 4; 18.2%). The rate of HER-2 positivity in metastases was 8% analogous to findings from Aprile et al[ 28 ] ( n = 50) with HER-2 overexpression in 12% of brain metastases. Furthermore, similarly high levels of concordance were reported for metastases and corresponding primary tumors in CRC patients [ 28 ][ 46 ].…”

Section: Discussionsupporting

confidence: 85%

“…HER-2 dimerizes preferentially with the HER-3 receptor initiating potential signal transduction leading to cell proliferation, angiogenesis and formation of metastases [ 33 ]. Several studies have reported varying expression levels of HER-2 and HER-3 and evaluated their correlation with clinico-pathological parameters and prognosis but with divergent results [ 23 ][ 28 ][ 29 ][ 34 ][ 35 ]. Still, in a variety of solid tumors, the HER-2 receptor represents an effective target for monoclonal antibodies such as trastuzumab being approved for metastatic gastric cancer, pertuzumab [ 36 ] or antibody-drug-conjugates such as T-DM-1 [ 37 ] and for small tyrosine kinase inhibitors like lapatinib [ 38 ] and afatinib [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…In several published meta-analyses it has been shown that HER-2 overexpression was correlated with decreased survival in CRC patients suggesting that HER-2 overexpression might not be a prognostic indicator [ 26 ][ 27 ]. In metastatic CRC, Aprile et al [ 28 ] reported a negative prognostic value of HER-2 expression in brain metastases.…”

Section: Introductionmentioning

confidence: 99%

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HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer

Styczen

Nagelmeier²,

Beißbarth

et al. 2015

Oncotarget

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ObjectiveIn this study, we evaluate the frequency of HER-2 and HER-3 expression in liver metastases from patients with colorectal cancer (CRLM). We analyzed the potential of HER-2 and HER-3 as therapeutic targets and evaluated their prognostic value.Patients and MethodsOverall 208 patients with CRLM were enrolled. HER-2 and HER-3 expression were determined in metastatic tissue of diagnostic punch biopsies (n = 29) or resection specimens (n = 179). The results of immunohistochemistry (IHC) scoring and In-situ-hybridization (ISH)-amplification were correlated with clinical parameters and for the 179 resected patients with cancer-specific (CSS) and overall survival (OS). The mean follow-up time was 56.7 months.ResultsPositivity of HER-2 status (IHC score 2+/ISH+ and IHC 3+) was found in 8.2% of CRLM. High expression of HER-3 (IHC score 2+ and IHC 3+) was detected in 75.0% of liver metastases. CSS after liver surgery was determined and was independent from the HER-2 status (p = 0.963); however HER-3 was prognostic with a favorable course for patients showing an overexpression of HER-3 (p = 0.037).ConclusionsHER-2 overexpression occurs in only 8% of patients with CRLM but with 75% of cases HER-3 is frequently overexpressed in CRLM. Therefore, HER-2 and particularly HER-3 could serve as novel targets to be addressed within multimodal treatment approaches.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer

Styczen

Nagelmeier²,

Beißbarth

et al. 2015

Oncotarget

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“…8 Activation of HER-2/neu, activates the pathways that play a primary role in cell proliferation and cell differentiation. Recent studies reported that deregulated HER-2 expression/activity is pivotal in oncogenic transformation, tumorigenesis, and metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…9 Previous studies showed overexpression of HER-2 in wide range of 0-84% among patients with CRC. 8-10 …”

Section: Introductionmentioning

confidence: 99%

Human Epidermal Growth Factor Receptor Expression in Colorectal Cancer and Its Relationship with Clinicopathological Characteristics

Torabizadeh¹,

Nosrati²,

Tahvildari³

2015

Middle East J Dig Dis

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BACKGROUND Some recent studies reported human epidermal growth factor receptor (HER-2/neu) as a marker that can be used in immunological studies of colorectal carcinoma for predicting the prognosis and the treatment. Therefore, we aimed to investigate the frequency of HER-2 expression in patients with colorectal cancer, and explore the relationship between clinicopathological prognostic factors and its expression based on immunohistochemical analysis. METHODS This study included 50 patients with a histologically proven diagnosis of colorectal carcinoma who received surgery at Imam Khomeini Hospital affiliated to Mazandaran University of Medical Sciences. First, HER-2/neu protein expressions were detected by immunohistochemistry and then the data extracted from recorded files. RESULTS The median age of the patients was 60.2±13.9 years (range: 25-93 years). There was no significant relationship between size of tumor, age, sex, lymph node metastases, distant metastasis, differentiation, and stage of the disease with positive expression of HER-2 in this study. CONCLUSION No significant relationship between expression of HER-2 and clinicopathological prognostic factors was found in our study. Further comprehensive and prospective trial with standard method to evaluate the role of HER-2 expression among patients with colorectal cancer is needed.

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Clinicopathological and prognostic significance of HER2 status in surgically resected colorectal liver metastases

Han

Wang

Zhang

et al. 2022

Journal of Surgical Oncology

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Background The clinicopathological and prognostic significance of human epidermal growth factor receptor 2 (HER2) status in surgically resected colorectal liver metastases (CRLM) remains uncertain. Methods HER2 expression was evaluated by immunohistochemical (IHC) in two CRLM tissue microarrays (TMAs). For samples with an IHC score of 2+ or 3+, fluorescence in situ hybridization (FISH) was performed to assess HER2 amplification. The association of HER2 amplification with clinicopathological parameters and prognosis was assessed using Fisher's exact test and Kaplan–Meier method, respectively. Results HER2 expression was consistent between primary tumor and liver metastases in 66.9% (85/127) cases (r = 0.643, p = 0.001). After FISH validation, HER2 amplification was identified in 6.25% (13/208) patients. HER2 amplification was significantly associated with age (p = 0.017), bilobar involvement (p = 0.005) and left‐sided RAS/RAF wild‐type status (p = 0.002). In the overall cohort, HER2 amplification was correlated with significantly worse relapse‐free survival (RFS). Further stratification revealed that among left‐sided RAS/RAF wild‐type cases, HER2 amplification was significantly associated with worse overall survival (OS) (30.2 vs. 50.9 months, p = 0.040) and RFS (5.77 vs. 19.97 months, p = 0.017). Conclusion HER2 amplification is more enriched in CRLMs with younger age, left‐sided RAS/RAF wild‐type, and bilobar involvement. Moreover, HER2 amplification predicts a poorer prognosis especially in left‐sided RAS/RAF wild‐type CRLMs.

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HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series

Cited by 14 publications

References 58 publications

HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer

HER-2 and HER-3 expression in liver metastases of patients with colorectal cancer

Human Epidermal Growth Factor Receptor Expression in Colorectal Cancer and Its Relationship with Clinicopathological Characteristics

Clinicopathological and prognostic significance of HER2 status in surgically resected colorectal liver metastases

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