HER2 status in advanced gastric carcinoma: A retrospective multicentric analysis from Sicily

Ieni,A.; Barresi,V.; Giuffrè,G.; Caruso,R. A.; Lanzafame,S.; Villari,L.; Salomone,E.; Roz,E.; Cabibi,D.; Franco,V.; Certo,G.; Labate,A.; Nagar,C.; Magliolo,E.; Broggi,B.; Fazzari,C.; Italia,F.; Tuccari,G.

doi:10.3892/ol.2013.1611

HER2 status in advanced gastric carcinoma: A retrospective multicentric analysis from Sicily

Authors:
- A. Ieni
- V. Barresi
- G. Giuffrè
- R. A. Caruso
- S. Lanzafame
- L. Villari
- E. Salomone
- E. Roz
- D. Cabibi
- V. Franco
- G. Certo
- A. Labate
- C. Nagar
- E. Magliolo
- B. Broggi
- C. Fazzari
- F. Italia
- G. Tuccari
View Affiliations

Affiliations: Department of Human Pathology, University of Messina, Messina, Sicily, Italy, Department of Anatomy, Diagnostic Pathology, Legal Medicine and Public Health, University of Catania, Catania, Sicily, Italy, Pathological Anatomy Unit, Vittorio Emanuele II University Hospital, Catania, Sicily, Italy, Health Home Service ‘La Maddalena’, Palermo, Sicily, Italy, Department of Human Pathology, University of Palermo, Palermo, Sicily, Italy, Health Home Service ‘IOMI‑Cappellani’, Messina, Sicily, Italy, Pathological Anatomy Unit, ASP 6 Palermo, Palermo, Sicily, Italy, Pathological Anatomy Unit, ASP 5 Messina, Messina, Sicily, Italy, Pathological Anatomy Unit, ASP 8 Siracusa, Siracusa, Sicily, Italy, Humanitas Center of Oncology, Catania, Sicily, Italy, Oncopathology Laboratory, Floridia, Siracusa, Sicily, Italy
Published online on: October 10, 2013 https://doi.org/10.3892/ol.2013.1611
Pages: 1591-1594

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

According to the ToGA trial, HER2 has been shown to be predictive for the success of treatment with trastuzumab in advanced gastric cancer (AGC). A number of studies have analyzed HER‑2/neu overexpression in gastric carcinoma and identified the rate of HER2 positivity to be markedly varied. To date, the prevalence of HER2 overexpression in Sicilian people with AGC is unknown. Therefore, in the present study, a retrospective immunohistochemical analysis of HER2 was performed in a cohort of 304 AGC samples that were obtained from the archives of 10 Sicilian anatomopathological diagnostic units in order to verify the positive rate of HER2‑positive cases. Furthermore, the characteristics of histotype, grade, stage and Ki‑67 expression were also analyzed. HER2 overexpression was encountered in 17.43% of all the gastric adenocarcinomas, which was consistent with the results that have been reported elsewhere in the literature. A progressive increase in HER2 overexpression was observed, from the poorly cohesive histotype to the tubular adenocarcinomas and gastric hepatoid adenocarcinomas. HER2 overexpression was significantly associated with a high grade, advanced stage and high Ki‑67 labeling index. Further investigations performed jointly by pathologists and oncologists within the geographical area of the present study should confirm that the association of trastuzumab with chemotherapy results in an improvement of survival in patients with AGC.

View Figures

View References

1	Ross JS and McKenna BJ: The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 19:554–568. 2001. View Article : Google Scholar : PubMed/NCBI
2	Latif Z, Watters AD, Bartlett JM, et al: Gene amplification and overexpression of HER2 in renal cell carcinoma. BJU Int. 89:5–9. 2002. View Article : Google Scholar : PubMed/NCBI
3	Leyland-Jones B: Trastuzumab therapy for the metastatic patient: does the primary match? Ann Oncol. 13:993–994. 2002. View Article : Google Scholar : PubMed/NCBI
4	Oxley JD, Winkler MH, Gillatt DA and Peat DS: Her-2/neu oncogene amplification in clinically localised prostate cancer. J Clin Pathol. 55:118–120. 2002. View Article : Google Scholar : PubMed/NCBI
5	Haddad R, Colevas AD, Krane JF, et al: Herceptin in patients with advanced or metastatic salivary gland carcinomas. A phase II study. Oral Oncol. 39:724–727. 2003. View Article : Google Scholar : PubMed/NCBI
6	Latif Z, Watters AD, Dunn I, et al: HER2/neu gene amplification and protein overexpression in G3 pT2 transitional cell carcinoma of the bladder: a role for anti-HER2 therapy? Eur J Cancer. 40:56–63. 2004. View Article : Google Scholar : PubMed/NCBI
7	Hansel DE, Ashfaq R, Rahman A, et al: A subset of pancreatic adenocarcinomas demonstrates coamplification of topoisomerase IIalpha and HER2/neu: use of immunolabeling and multicolor FISH for potential patient screening and treatment. Am J Clin Pathol. 123:28–35. 2005. View Article : Google Scholar
8	Ugocsai K, Mándoky L, Tiszlavicz L and Molnár J: Investigation of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 25:3061–3066. 2005.PubMed/NCBI
9	Tapia C, Savic S, Wagner U, et al: HER2 gene status in primary breast cancers and matched distant metastases. Breast Cancer Res. 9:R312007. View Article : Google Scholar : PubMed/NCBI
10	Bang YJ, Van Cutsem E, Feyereislova A, et al; 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. 376:687–697. 2010. View Article : Google Scholar
11	Tanner M, Hollmén M, Junttila TT, et al: Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 16:273–278. 2005. View Article : Google Scholar : PubMed/NCBI
12	Hede K: Gastric cancer: trastuzumab trial results spur search for other targets. J Natl Cancer Inst. 101:1306–1307. 2009. View Article : Google Scholar : PubMed/NCBI
13	Moelans CB, Milne AN, Morsink FH, et al: Low frequency of HER2 amplification and overexpression in early onset gastric cancer. Cell Oncol (Dordr). 34:89–95. 2011. View Article : Google Scholar : PubMed/NCBI
14	Gravalos C and Jimeno A: HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 19:1523–1529. 2008. View Article : Google Scholar : PubMed/NCBI
15	Rüschoff J, Dietel M, Baretton G, et al: HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 457:299–307. 2010.PubMed/NCBI
16	Giuffrè G, Ieni A, Barresi V, et al: HER2 status in unusual histological variants of gastric adenocarcinomas. J Clin Pathol. 65:237–241. 2012.PubMed/NCBI
17	Crocetti E; AIRTUM Working Group. Incidence and mortality cancer trends of the Italian Network of Cancer Registries (AIRTUM), 1998–2005. Epidemiol Prev. 33(Suppl 1): 36–37. 2009.
18	Bosman FT, Carneiro F, Hruban RH and Theise ND: WHO Classification of Tumours of the Digestive System. 4th edition. IARC; Lyon, France: 2010
19	Albarello L, Pecciarini L and Doglioni C: HER2 testing in gastric cancer. Adv Anat Pathol. 18:53–59. 2011. View Article : Google Scholar
20	Barros-Silva JD, Leitão D, Afonso L, et al: Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients. Br J Cancer. 100:487–493. 2009. View Article : Google Scholar
21	Marx AH, Tharun L, Muth J, et al: HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol. 40:769–777. 2009. View Article : Google Scholar : PubMed/NCBI
22	Grabsch H, Sivakumar S, Gray S, et al: HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic values - conclusions from 924 cases of two independent series. Cell Oncol. 32:57–65. 2010.PubMed/NCBI
23	Yan B, Yau EX, Bte Omar SS, et al: A study of HER2 gene amplification and protein expression in gastric cancer. J Clin Pathol. 63:839–842. 2010. View Article : Google Scholar : PubMed/NCBI
24	Jørgensen JT: Targeted HER2 treatment in advanced gastric cancer. Oncology. 78:26–33. 2010.
25	Hofmann M, Stoss O, Shi D, et al: Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 52:797–805. 2008. View Article : Google Scholar : PubMed/NCBI
26	Yano T, Doi T, Ohtsu A, et al: Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep. 15:65–71. 2006.PubMed/NCBI
27	Kumashiro Y, Yao T, Aishima S, et al: Hepatoid adenocarcinoma of the stomach: histogenesis and progression in association with intestinal phenotype. Hum Pathol. 38:857–863. 2007. View Article : Google Scholar : PubMed/NCBI
28	Gálvez-Muñoz E, Gallego-Plazas J, Gonzalez-Orozco V, et al: Hepatoid adenocarcinoma of the stomach - a different histology for not so different gastric adenocarcinoma: a case report. Int Semin Surg Oncol. 6:132009.PubMed/NCBI
29	Jouret-Mourin A, Hoorens A, De Hertogh G, et al: Analysis of HER2 expression and gene amplification in adenocarcinoma of the stomach and the gastro-oesophageal junction: rationale for the Belgian way of working. Acta Gastroenterol Belg. 75:9–13. 2012.PubMed/NCBI