Overexpression of c-ErbB-2 Protein in Gastric Cancer by Immunohistochemical Stain

Lee, Hye Ran; Kim, Joo Hang; Uhm, Hyo Dong; Ahn, Joong Bae; Rha, Sun Young; Cho, Jae Yong; Lee, Jong In; Lee, Kyong Hee; Chung, Hyun Cheol; Roh, Jae Kyong; Min, Jin Sik; Shin, Dong Hwan; Kim, Byung Soo; Hong, Soon Won; Choi, Jin Hyuk

doi:10.1159/000227559

Cited by 30 publications

(17 citation statements)

References 12 publications

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“…(25) 126 (29) 17 (27) 125 (29) Extended gastrectomy 8 (13) 48 (11) 8 (13) 48 (11) Bormann type 0.32 0.41 IV 5 (8) 58 (13) 5 (8) 55 (13) In previous studies, the overall frequency of ERBB2 overexpression in gastric cancer ranged from 7 to 53%. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] This wide range of overexpression of ERBB2 might be explained by the study cohort, localization within the stomach, histological subtype or interpretation of results. ERBB2 positivity is significantly higher in intestinal histology (34%) and gastro-esophageal tumors (34%) than in diffusetype (6%) and gastric locations (20%).…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have reported that ERBB2 is a poor prognostic factor in gastric carcinoma. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] However, Grabsch et al, 35 Kim et al, 37 and Barros-Silva et al 38 reported that ERBB2 is not associated with prognosis in large series consisting of 924, 248, and 463 patients, respectively. The disagreement is probably related to differences in sample size, patient characteristics, and interpretation of results.…”

Section: Discussionmentioning

confidence: 99%

“…2 There is growing evidence that ERBB2 is an important biomarker and key driver of tumorigenesis in gastric cancer, showing amplification or overexpression in 7-53% of tumors. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] A recent multicenter phase III (ToGA) study showed a significant improvement in overall survival in patients with ERBB2 þ advanced gastro-esophageal and gastric adenocarcinoma who were treated with chemotherapy plus trastuzumab compared with patients who received chemotherapy alone. 3 Among various methods for measuring ERBB2 in carcinoma tissue, immunohistochemistry is the most attractive routine test based on issues of cost, convenience, and biological relevance.…”

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confidence: 99%

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Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas

Cho

Park

et al. 2013

Modern Pathology

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Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2 þ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be performed in both primary and distant metastatic sites. The human protooncogene ERBB2 (commonly referred to as HER2) is a 185-kDa transmembrane tyrosine kinase receptor and a member of the epidermal growth factor receptor family. 1 Overexpression of ERBB2 has been found to promote tumorigenesis and is involved in the pathogenesis of several human cancers. Amplification of ERBB2 gene and overexpression of ERBB2 protein in gastric carcinoma were first described in 1986, and since then a number of studies have confirmed these findings. 2 There is growing evidence that ERBB2 is an important biomarker and key driver of tumorigenesis in gastric cancer, showing amplification or overexpression in 7-53% of tumors. 3-20 A recent

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas

Cho

Park

et al. 2013

Modern Pathology

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“…Tateishi et al (18) did not detect significant difference in the 5-year survival rates of HER-2 positive and negative patients. Lee et al (22) determined that 27.4% of 225 patients who underwent locally advanced curative gastric resection showed increased HER-2 expression and that there was no significant difference in overall survival between HER-2 positive and negative groups. Sasano et al (23) reported the HER-2 expression rate as 27%, but there was no correlation with prognosis.…”

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confidence: 99%

HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters

Uprak

Attaallah

Çelikel

et al. 2015

UCD

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Objective: Human epidermal growth factor-2 (HER-2) overexpression has prognostic value in breast cancer. However, the significance of HER-2 positivity in gastric cancer is controversial. In this study, we investigated the frequency of overexpression of HER-2 and its relationship with clinicopathological findings and impact on survival in gastric cancer. Material and Methods:Gastric cancer patients, operated in Marmara University Faculty of Medicine, Pendik Training and Research Hospital, General Surgery Department, between January 2012-December 2013 were enrolled in this study. Medical records were retrospectively evaluated. Tissue samples were stained by immunohistochemistry (IHC) method, and were followed by fluorescence in situ hybridization (FISH) in those with positive results. HER-2 expression rates and its association with other histopathological features and survival have been analyzed.Results: 135 patients were enrolled in the study, with 88 (65%) male and 47 (35%) female patients. The median age was 61 (29-84) years. Only 11 patients (8%) were positive for HER-2. HER-2 positive patients were similar to negative patients in terms of age, gender, tumor size, tumor location, tumor T stage, lymph node metastasis, histological type, differentiation, lymphovascular invasion, perinodal, perineural invasion and stage. No significant difference was detected on 1 and 2-year overall and disease-free survival rates between receptor positive and negative groups. Conclusion:Consistent with the literature data, HER-2 positivity rate in this study was approximately 8%, but this positivity has not been found to be associated with either clinical and pathological parameters or overall and disease-free survival.

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“…For erbB2 protein, positive rates for erbB2 immunoreactivity range from 10 to 50% for the human gastric cancers that have been studied, and is higher for welldierentiated gastric cancers (Kameda et al, 1990;Lee et al, 1996;Motojima et al, 1994;Orita et al, 1997;Uchino et al, 1993;Yonemura et al, 1991a). The expression of erbB2 protein is a signi®cant independent risk factor for long term survival, disease recurrence and lymph-node metastasis (Lin et al, 1995;Motojima et al, 1994;Orita et al, 1997;Sanz-Ortega et al, 2000;Yonemura et al, 1991a).…”

Section: Protein Localization By Immunohistochemistrymentioning

confidence: 99%

Tyrosine kinases and gastric cancer

et al. 2000

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Carcinoma of the stomach is one of the most prevalent cancer types in the world today. Two major forms of gastric cancer are distinguished according to their morphological and clinicopathological classi®cations (well dierentiated/intestinal type and poorly dierentiated/diuse type), characteristics that could also be attributed to the altered expression of dierent types of oncogenes or tumor suppressor genes. Signi®cant dierences exist for gastric cancer incidence comparing people of dierent ethnic origins, implicating various genetic and epigenetic factors for gastric oncogenesis. There are only a limited number of molecular markers available for gastric cancer detection and prognostic evaluation, among which are tyrosine kinases. There is convincing evidence that tyrosine kinases are involved in oncogenesis and disease progression for many human cancers. Ampli®cations of certain tyrosine kinases (cmet, k-sam and erbB2/neu) have been associated with human gastric cancer progression. Alternatively spliced transcripts and enhanced protein-expression levels for some of these tyrosine kinases are correlated with clinical outcomes for gastric cancer patients. With advent of high throughput techniques, it is now possible to detect nearly all expressed tyrosine kinases in a single screen. This increases the chance to identify additional tyrosine kinases as predictive markers for gastric cancers. In this article, we will ®rst review the literature data concerning certain tyrosine kinases implicated in gastric carcinogenesis and then summarize more recent work which provide comprehensive tyrosine kinase pro®les for gastric cancer specimens and cell lines. Two new gastric cancer molecular markers (tie-1 and mkk4) have been identi®ed through the use of these pro®les and demonstrated eective as clinical prognostic indicators. Oncogene (2000) 19, 5680 ± 5689.

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Overexpression of c-ErbB-2 Protein in Gastric Cancer by Immunohistochemical Stain

Cited by 30 publications

References 12 publications

Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas

Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas

HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters

Tyrosine kinases and gastric cancer

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