Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes

Diagnostic Pathology

Tadatoshi Takayama²  Hiroshi Suda²  Megumu Watanabe²  Hidenori Tamegai²  Tomoya Funada²  Yoshiaki Mihara²  Noriaki Kanamori²  Shinobu Masuda¹  Masashi Fujii²  Mitsugu Kochi² 

[1] Department of Pathology, Nihon University School of Medicine, Tokyo, Japan;Department of Digestive Surgery, Nihon University School of Medicine, 30-1OHyaguchi Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan

关键词: Primary tumor;    Lymph node metastasis;    HER2;    Gastric cancer;   

Others  :  1093009
DOI  :  10.1186/1746-1596-8-191

 received in 2013-07-06, accepted in 2013-11-12,  发布年份 2013

【 摘 要 】

Background

The aim of this study was to investigate how differences in expression of HER2 between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents.

Methods

The analysis was conducted in 102 patients who underwent surgical resection for primary gastric cancers (PGCs; adenocarcinoma, intestinal type) with synchronous LNMs. HER2 gene status and protein expression were investigated by immunohistochemistry (IHC) in all patients; fluorescence in situ hybridization (FISH) was performed in 22 patients. The correlation between HER2 gene status in PGCs and their LNMs was evaluated.

Results

Positive HER2 expression as detected by IHC + FISH was observed in 27/102 PGC samples (26.5%) and 29/102 LNM samples (28.4%). HER2 amplification status in 102 paired PGC and LNM samples as evaluated by FISH + IHC was concordant in 92 patients (90.2%), 69 (67.6%) were unamplified and 23/102 (22.5%) were amplified at both sites, and discordant in 10 patients (9.8%), 4 (3.9%) were positive for PGC and negative for LNM, while 6 (5.9%) were positive for LNM and negative for PGC. The results of FISH + IHC showed very strong concordance in HER2 status between the PGC and LNM groups (k = 0.754).

Conclusion

The high concordance between HER2 results for PGCs and their LNMs indicates that assessment of HER2 status in the primary cancer alone is a reliable basis for deciding treatment with anti-HER2 agents in patients with LNMs from gastric adenocarcinoma.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9365749431029643 webcite.

【 授权许可】

   
2013 Kochi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Allgayer H, Babic R, Gruetzner KU, Tarabichi A, Schildberg FW: Heiss MM: c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J ClinOncol 2000, 18:2201-2209.
• [2]Barros-Silva JD, Leitão D, Afonso L, Vieira J, Dinis-Ribeiro M, Fragoso M, Bento MJ, Santos L, Ferreira P, Rêgo S, Brandão C, Carneiro F, Lopes C, Schmitt F, Teixeira MR: Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer 2009, 100:487-493.
• [3]Jørgensen JT: Targeted HER2 treatment in advanced gastric cancer. Oncology 2010, 78:26-33.
• [4]Lee HR, Kim JH, Uhm HD, Ahn JB, Rha SY, Cho JY, Lee JI, Lee KH, Chung HC, Roh JK, Min JS, Lee KS, Shin DH, Kim BS, Hong SW, Choi JH: Overexpression of c-ErbB-2 protein in gastric cancer by immunohistochemical stain. Oncology 1996, 53:192-197.
• [5]Lee KE, Lee HJ, Kim YH, Yu HJ, Yang HK, Kim WH, Lee KU, Choe KJ, Kim JP: Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer. Jpn J ClinOncol 2003, 33:173-179.
• [6]Ooi A, Kobayashi M, Mai M, Nakanishi I: Amplification of c-erbB-2 in gastric cancer: detection in formalin-fixed, paraffin-embedded tissue by fluorescence in situ hybridization. Lab Invest 1998, 78:345-358.
• [7]Yano T, Doi T, Ohtsu A, Boku N, Hashizume K, Nakanishi M, Ochiai A: Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep 2006, 15:65-71.
• [8]Yu GZ, Chen Y, Wang JJ: Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance. J Cancer Res ClinOncol 2009, 135:1331-1339.
• [9]Shan L, Ying J, Lu N: HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagn Pathol 2013, 9:76.
• [10]Laurinaviciene A, Dasevicius D, Ostapenko V, Jarmalaite S, Lazutka J: Laurinavicius: a ABCG2 is associated with HER-2 expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma. Diagn Pathol 2011, 23:87.
• [11]Vogel UF: Confirmation of a low HER2 positivity rate of breast carcinomas - limitations of immunohistochemistry and in situ hybridization. Diagn Pathol 2010, 29:50.
• [12]Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK: ToGA Trial Investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010, 376:687-697.
• [13]Yenidunya S, Bayrak R, Haltas H: Predictive value of pathological and immunohistochemical parameters for axillary lymph node metastasis in breast carcinoma. Diagn Pathol 2011, 13:18.
• [14]Xiang L, Su P, Xia S, Liu Z, Wang Y, Gao P, Zhou G: ABCG2 is associated with HER-2 expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma. Diagn Pathol 2011, 27:90.
• [15]Simon R, Nocito A, Hübscher T, Bucher C, Torhorst J, Schraml P, Bubendorf L, Mihatsch MM, Moch H, Wilber K, Schötzau A, Kononen J, Sauter G: Patterns of her-2/neu amplification and overexpression in primary and metastatic breast cancer. J Natl Cancer Inst 2001, 93:1141-1146.
• [16]Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, Ochiai A, Rüschoff J, Henkel T: Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008, 52:797-805.
• [17]Fukushige S, Matsubara K, Yoshida M, Sasaki M, Suzuki T, Semba K, Toyoshima K, Yamamoto T: Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. Mol Cell Biol 1986, 6:955-958.
• [18]Sakai K, Mori S, Kawamoto T, Taniguchi S, Kobori O, Morioka Y, Kuroki T, Kano K: Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas. J Natl Cancer Inst 1986, 77:1047-1052.
• [19]Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, Miyazaki I, Endou Y, Tanaka M, Sasaki T: Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric ancer. Cancer Res 1991, 51:1034-1038.
• [20]Yonemura Y, Ninomiya I, Ohoyama S, Fushida S, Kimura H, Tsugawa K, Kamata T, Yamaguchi A, Miyazaki I, Endou Y: Correlation of c-erbB-2 protein expression and lymph node status in early gastric cancer. Oncology 1992, 49:363-367.
• [21]Bozzetti C, Negri FV, Lagrasta CA, Crafa P, Bassano C, Tamagnini I, Gardini G, Nizzoli R, Leonardi F, Gasparro D, Camisa R, Cavalli S, Silini EM, Ardizzoni A: Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer 2011, 26:1372-6.
• [22]Marx AH, Tharun L, Muth J, Dancau AM, Simon R, Yekebas E, Kaifi JT, Mirlacher M, Brümmendorf TH, Bokemeyer C, Izbicki JR, Sauter G: HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol 2009, 40:769-777.
• [23]Kim MA, Lee HJ, Yang HK, Bang YJ, Kim WH: Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinoma. Histopathology 2011, 59:822-831.
• [24]Kim JH, Kim MA, Lee HS, Kim WH: Comparative analysis of protein expressions in primary and metastatic gastric carcinomas. Hum Pathol 2009, 40:314-322.