HER2 status in advanced gastric cancer: the dark side of the moon

Antonio Ieni, Giuseppe Angelico, Rosalba De Sarro, Giuseppe Speciale, Giuseppe Giuffrè, Giovanni Tuccari

Abstract


The present study evaluated HER2 status between primary gastric and paired metastatic disease to lymph nodes, collecting 62 formalin-fixed paraffin-embedded representative tissue blocks as well as synchronous metastatic lymph nodes by immunohistochemistry and FISH. The discordant HER2 pooled rate, regardless either negative or positive conversion, was 9.26% in primary gastric carcinoma and corresponding nodal metastasis. Moreover, a high level concordance in HER2 expression between primary carcinoma and synchronous metastatic lymph nodes was achieved in 90.74% of cases. In our opinion, the observed event of discordant HER2 status should be ascribed to intra-tumor heterogeneity. In any case, the shift from positive to negative HER2 expression suggests that Trastuzumab could be the targeted treatment choice, while the opposite shift should be evaluated by a simultaneous HER2 determination in both primary and metastatic lymph nodes.

Keywords


HER2; advanced gastric cancer; lymph node; metastasis; prognosis

Full Text:

PDF

References


Ieni, A., Giuffrè, G., Lanzafame, S., Nuciforo, G., Curduman, M., Villari, L., Roz, E., Certo, G., Cabibi, D., Salomone, E., Labate, A., Messina, D., Franco, V., Adamo, V., Tuccari, G. (2012). Morphological and biomolecular characteristics of subcentimetric invasive breast carcinomas in Sicily: A multicentre retrospective study in relation to trastuzumab treatment. Oncol Lett, 3(1), 141-146.

Ballinger, T.J., Sanders, M.E., Abramson, V.G. (2015). Current HER2 Testing Recommendations and Clinical Relevance as a Predictor of Response to Targeted Therapy. Clin Breast Cancer, 15(3), 171-180. Al-Momani, H., Barnes, R., El-Hadi, A., Shah, R., Lewis, W.G., Edwards, P. (2012). Human epidermal growth factor receptor-2 in oesophageal cancers: an observational study. World J Gastroenterol, 18(44), 6447-6451.

Bang, Y.J., Van, C.E., Feyereislova, A., Chung, H.C., Shen, L., Sawaki, A., Lordick, F., Ohtsu, A., Omuro, Y., Satoh, T., Aprile, G., Kulikov, E., Hill, J., Lehle, M., Rüschoff, J., Kang, Y.K. (2010). Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 376(9742), 687-697.

Koopman, T., Smits, M.M., Louwen, M., Hage, M., Boot, H., Imholz, A.L. (2015). HER2 positivity in gastric and esophageal adenocarcinoma: clinicopathological analysis and comparison. J Cancer Res Clin Oncol, 141(8), 1343-1351.

Giuffrè, G., Ieni, A., Barresi, V., Caruso, R.A., Tuccari, G. (2012). HER2 status in unusual histological variants of gastric adenocarcinomas. J Clin Pathol, 65(3), 237-41.

Barresi, V., Giuffrè, G., Caruso, R.A., Tuccari, G. (2013). HER2 status in rarer histologic types of gastric adenocarcinomas. Arch Pathol Lab Med, 137(6), 741.

Bilous, M., Osamura, R.Y., Rüschoff, J., van de Vijver, M., Hanna, W., Penault-Llorca, F., Roche, P. (2010). HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol, 41(2), 304-305.

Rüschoff, J., Hanna, W., Bilous, M., Hofmann, M., Osamura, R.Y., Penault-Llorca, F., van de Vijver, M., Viale, G. (2012). HER2 testing in gastric cancer: A practical approach. Mod Pathol, 25(5), 637-650.

Bozzetti, C., Negri, F.V., Lagrasta, C.A., Crafa, P., Bassano, C., Tamagnini, I., Gardini, G., Nizzoli, R., Leonardi, F., Gasparro, D., Camisa, R., Cavalli, S., Silini, E.M., Ardizzoni, A. (2011). Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma. Br J Cancer, 104(12), 1929.

Wang, T., Hsieh, E.T, Henry, P., Hanna, W., Streutker, C.J., Grin, A. (2014). Matched biopsy and resection specimens of gastric and gastroesophageal adenocarcinoma show high concordance in HER2 status. Hum Pathol, 45(5), 970-975.

Hofmann, M., Stoss, O., Shi, D., Büttner, R., van de Vijver, M., Kim, W., Ochiai, A., Rüschoff, J., Henkel, T. (2008). Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology, 52(7), 797-805.

Ieni, A,, Barresi, V,, Caltabiano, R., Cascone, A.M., Del Sordo, R., Cabibi, D., Zeppa, P., Lanzafame, S., Sidoni, A., Franco, V., Tuccari, G. (2014). Discordance rate of HER2 status in primary breast carcinomas versus synchronous axillary lymph node metastases: A multicenter retrospective investigation. Onco Targets Ther, 7, 1267-1272.

Ieni, A., Barresi, V., Caltabiano, R., Caleo, A., Bonetti, L.R., Lanzafame, S., Zeppa, P., Caruso, R.A., Tuccari, G. (2014). Discordance Rate of HER2 Status in Primary Gastric Carcinomas and Synchronous Lymph Node Metastases: A Multicenter Retrospective Analysis. Int J Mol Sci, 15(12), 22331-22341.

Ieni, A., Barresi, V., Branca, G., Licata, L., Caruso, R.A., Tuccari, G. (2015). Changes in human epidermal growth factor receptor 2 status between primary breast/gastric carcinomas and synchronous metastatic lymph nodes: how can we explain them?. J Cancer Metastasis Treat, 1, 21-26.




DOI: https://doi.org/10.6092/1828-6550/APMB.105.1.2017.A9

Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 Ieni Antonio, Giuseppe Angelico, Rosalba De Sarro, Giuseppe Speciale, Giuseppe Giuffrè, Giovanni Tuccari

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.