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Is Her-2 Status in the Primary Tumor Correlated with Matched Lymph Node Metastases in Patients with Gastric Cancer Undergoing Curative Gastrectomy?

  • Published : 2015.01.22

Abstract

Background: HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastatic nodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expression in the primary tumor and lymph node metastases for patients with gastric cancer. Materials and Methods: Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymph node metastasis upon pathological examination were included. Histopathological samples were obtained from biopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and silver in situ hybridization (SISH). Results: Sixty-four (79%) patients were SISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors and lymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrated discordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance was significantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worse survival rates than concordant patients, the differences were not significant (p>0.05).Conclusions: Our study indicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primary tumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefit from trastuzumab, and it would therefore help guide decision-making processes in administering treatment.

Keywords

References

  1. Arteaga CL, Sliwkowski MX, Osborne CK, et al (2011). Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol, 9, 16-32. https://doi.org/10.1038/nrclinonc.2011.177
  2. Bang YJ, Van Cutsem E, Feyereislova A, et al (2010). ToGA trial investigators. trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophagealjunction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 28, 687-97.
  3. Bozzetti C, Negri FV, Lagrasta CA, et al (2011). Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer, 26, 1372-6.
  4. Czyzewska J, Guzinska-Ustymowicz K, Kemona A (2009). Correlation of c-erbB-2, EGF and EGFR expression with postoperative survival of patients with advanced carcinoma of the stomach. Folia Histochem Cytobiol, 47, 653-61.
  5. Hofmann M, Stoss O, Shi D, et al (2008). Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology, 52, 797-805. https://doi.org/10.1111/j.1365-2559.2008.03028.x
  6. Im SA, Kim JW, Kim JS, et al (2011). Clinicopathologic characteristics of patients with stage III/IV (M(0)) advanced gastric cancer, according to HER2 status assessed by immunohistochemistry and fluorescence insitu hybridization. Diagn Mol Pathol, 20, 94-100. https://doi.org/10.1097/PDM.0b013e3181fc02b7
  7. Kim MA, Jung EJ, Lee HS, et al (2007). Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situhybridization, and real-time quantitative polymerase chain reaction. Hum Pathol, 38, 1386-93. https://doi.org/10.1016/j.humpath.2007.02.005
  8. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  9. Khasraw M, Bell R (2012). Primary systemic therapy in HER2-amplified breast cancer: a clinical review. Expert Rev Anticancer Ther, 12, 1005-13. https://doi.org/10.1586/era.12.62
  10. Kim MA, Jung EJ, Lee HS, et al (2007). Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situhybridization, and real-time quantitative polymerase chain reaction. Hum Pathol, 38, 1386-93. https://doi.org/10.1016/j.humpath.2007.02.005
  11. Kim SY, Kim HP, Kim YJ, et al (2008). Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin. Int J Oncol, 32, 89-95.
  12. Marx AH, Tharun L, Muth J, et al (2009). HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol, 40, 769-77. https://doi.org/10.1016/j.humpath.2008.11.014
  13. Motojima K, Furui J, Kohara N, et al (1994). c-erbB-2 expression in well-differentiated adenocarcinoma of the stomach predicts shorter survival after curative resection. Surgery, 115, 349-54.
  14. Nakajima M, Sawada H, Yamada Y, et al (1999). The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer, 85, 1894-902. https://doi.org/10.1002/(SICI)1097-0142(19990501)85:9<1894::AID-CNCR3>3.0.CO;2-J
  15. Orita H, Maehara Y, Emi Y, et al (1997). Kakeji Y, Baba H, Korenaga D. c-erbB-2 expression is predictive for lymphatic spread of clinical gastric carcinoma. Hepatogastroenterology, 44, 294-8.
  16. Pusztai L, Viale G, Kelly CM, et al (2010). Estrogen and HER-2 receptor discordance between primary breast cancer and metastasis. Oncologist, 15, 1164-8. https://doi.org/10.1634/theoncologist.2010-0059
  17. Sawaki A, Ohashi Y, Omuro Y, et al (2012). Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the trastuzumab for gastric cancer (ToGA) study. GastricCancer, 15, 313-22.
  18. Simon R, Nocito A, Hubscher T, et al (2001). Patterns of her-2/neu amplification and overexpression in primary and metastatic breast cancer. J Natl Cancer Inst, 93, 1141-6. https://doi.org/10.1093/jnci/93.15.1141
  19. Tsigris C, Karayiannakis AJ, Syrigos KN, et al (2002). Clinical significance of soluble c-erbB-2 levels in the serum and urine of patients with gastric cancer. Anti Cancer Res, 22, 3061-65.
  20. Wagner AD, Grothe W, Haerting J, et al (2006). Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol, 24, 2903-9. https://doi.org/10.1200/JCO.2005.05.0245
  21. Wang J, Saukel GW, Garberoglio CA, et al (2010). Pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in gastric cancer: a case report. J Hematol Oncol, 9, 3-31.
  22. Wang S, Zheng G, Chen L, et al (2011). Effect of HER-2/neu over-expression on prognosis in gastric cancer: a meta-analysis. Asian Pac J Cancer Prev.12, 1417-23.
  23. Xu R, Perle MA, Inghirami G, et al (2002). Amplification of Her-2/neu gene in Her-2/neu-overexpressing and nonexpressing breast carcinomas and their synchronous benign, premalignant, and metastatic lesions detected by FISH in archival material. Mod Pathol, 15, 116-24. https://doi.org/10.1038/modpathol.3880503
  24. Yano T, Doi T, Ohtsu A, et al (2006). Comparison of HER2 gene amplification assessed by fluorescence insitu hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep, 15, 65-71.
  25. Yu Ch, Xu S, Ni X, et al (2007). Study on the relationship between P-glycoprotein (P-gp) and c-erbB-2 expression in gastric carcinoma. Chinese-German J Clin Oncol, 6, 222-4. https://doi.org/10.1007/s10330-006-0577-8

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