Abstract is not required for Editorialis not required for Editorial (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 6 No. 8, August 2015. ISSN – [0976-3198] Int J Case Rep Images 2015;6(8):530–533. www.ijcasereportsandimages.com Barresi et al. 530 CASE REPORT OPEN ACCESS HER2 status in premalignant dysplastic gastric lesions Valeria Barresi, Antonio Ieni, Giovanni Tuccari The epidermal growth factor receptor family is constituted by four members with similar structures: HER1/erbB1, HER2/erbB2, HER3/erbB3 and HER4/ erbB4. These receptors play an important role in the processes of proliferation and differentiation of normal cells [1]. The binding of the ligand to these receptors causes the creation of homodimers and heterodimers as well as the activation of downstream signaling pathways [1]. Hence, any aberrations in their structure or function can cause transformation of normal cells to malignant cells with consequent tumor development and progression [1]. However, on the basis of results from an international randomized controlled trial (ToGA), the patients with advanced gastric adenocarcinoma (GC) positive for HER2 over-expression could be eligible for a target treatment with trastuzumab [2]. A significant reduction in the risk of mortality was appreciable when trastuzumab was added to the chemotherapy regimen [2]. There is general agreement with regard to a higher HER2 positivity in gastroesophageal junction cancer (24–35%) compared with GC (9.5–21%) [3]. The rate of HER2 immunoreactivity seemed to be vary variable in relation to the different neoplastic histotype of the stomach [4]. Generally, all studies have reported a prevalence of HER2 amplification in advanced GC of Valeria Barresi1, Antonio Ieni1, Giovanni Tuccari1 Affiliations: 1Azienda Ospedaliera Universitaria “Gaetano Martino” and Department of Human Pathology “Gaetano Barresi”, Section of Anatomic Pathology, University of Messina, Messina 98123, Italy. Corresponding Author: Giovanni Tuccari, MD, Full Professor of Pathology Department of Human Pathology, “Gaetano Barresi” University of Messina, A.O.U. “Policlinico G. Martino” Pad. D, Via Consolare Valeria, 98125 – MESSINA (Italy); Ph: +39-90-2212539; Fax:+39-90-2928150 E-mail: tuccari@unime.it Received: 16 June 2015 Published: 01 August 2015 EdiTO iAlS OPEN A CE S intestinal type (81.6–91%) in comparison with diffuse or mixed ones (4–7.9%) [4]. In addition, a progressive increase in HER2 overexpression has been appreciated moving from the poorly cohesive WHO histotype to mitochondrion-rich adenocarcinomas (MRC), tubular adenocarcinomas and hepatoid carcinomas (HAS), these latter representing the top rate of HER2 positivity, characterized by an extremely poor prognosis [4]. Furthermore, HER2 overexpression was also significantly associated with a high grade, advanced stage and high Ki67-LI value, becoming thus an additional morphological parameter able to affect the mortality of patients with GC [5]. Finally, some investigations have been recently reported regarding the concordance of HER status in primary gastric cancer and corresponding lymph nodes or distant metastases, with either positive or negative conversion in HER2 overexpression [6, 7]. Generally speaking, chronic atrophic gastritis and intestinal metaplasia of the stomach have been regarded to as pre-neoplastic lesions, even if data from literature points towards the existence of other pathways, in which intestinal metaplasia may not play a role, as described by Japanese authors [8]. However, the true precancerous gastric lesion should be considered dysplasia, which includes cellular and structural atypia, also codified under the term intraepithelial neoplasia (IEN), a pathological condition that lies between atrophic gastritis and GC [9]. It is well known, that IEN may develop in the gastric or intestinal metaplastic epithelium and it can be categorized into four categories: indefinite for intraepithelial neoplasia, low-grade intraepithelial neoplasia (LG-IEN), high-grade intraepithelial neoplasia (HG-IEN) and suspicious for invasive cancer [10]. The IEN histological distinction as low or high-grade depends on the severity of architectural and cytological atypia. In LG-IEN, the mucosal structure is only faintly modified maintaining tubular differentiation with the proliferative zone limited to the outward portion, whereas HG-IEN exhibits increasing distortion of the mucosal architecture, resulting in crowded possibly irregular glands with obvious cellular atypia and proliferative activity distributed throughout the lesion [10]. High-grade intraepithelial neoplasia is