Nazar and colleagues reported a normal

Nazar and colleagues reported a normal HER2 gene number in 13 primary and 2 recurrent ethmoid sinus adenocarcinomas, without any histological and immunohistochemical characterization, so a comparison with the present findings is impossible [14]. More recently, 552 head and neck carcinomas have been tested for HER2 status with both IHC and ISH techniques [9]. However, the histological types of the tumors were not reported, preventing a comparison with the present findings. In the absence of a standardized method for HER2 evaluation in sinonasal ITAC, we chose to assess HER2 using the four-tier immunohistochemical score developed for gastroesophageal cancer given the similar morphology between intestinal type gastroesophageal carcinoma and ITAC [25]. This score is standardized, widely used, and reproducible. Among our cases, only one ITAC showed a 2 + HER2 score, and 6 of 43 cases were scored 1 + . Contrary with previous studies [11,12], we found lower HER2 expression levels with IHC. This variability could be explained by the difference in VU590 hydrochloride sale and diverse scoring systems. These previous studies used different clones than in our study, i.e. mouse monoclonal antibody mAbl (by Triton Diagnostic) [11], and HercepTest with a rabbit anti-human antibody [12]. Additionally, with regards to the scoring systems, the HER2 IHC criteria of the stomach are less restrictive than the breast. The percentage of positive cells (>10%) used as a threshold is the same in these scoring systems and is coupled with a basolateral expression in the stomach, whereas requires a circumferential expression in the breast. So, we would not expect 3+ cases in our series using the breast scoring system. At the genetic level, we found no evidence of gene amplification in the complete series, but this result cannot be compared with the previous studies explained above. Therefore, the present is the first series of homogeneous sinonasal ITACs tested for HER2 status by cytogenetic technique. Moreover, overall concordance between IHC and CISH was excellent. This result supports HER2 IHC as a reliable tool in ITAC, as in breast and gastroesophageal cancer. Besides morphological and immunophenotypical similarities between CRC and sinonasal adenocarcinomas, it is important to also consider the genetic differences [[30], [31], [32], [33]]. The present study is in line with the idea that they are different entities, however, the number of cases does not supply enough evidence on this topic. Patients diagnosed with ITAC, as other histological types in this anatomical site, have a poor prognosis, especially after relapse. The analysis of our study confirms that sinonasal ITACs are quite locally aggressive tumors, which rarely metastasize, often occurring in male patients with occupational exposure, mostly to wood and leather dust. The recurrence rate in our series (18.6%) is in line with existing literature, in the lower part of the reported range (17.6–49.6%) [34]. Four patients (9.3%) died of disease, 3 of which had been exposed to wood dust and relapsed before exitus, and all patients had been treated with surgical excision and adjuvant radiotherapy. Two cases were solid type, and the other 2 were colonic type ITACs. However the number of cases is too small to suggest any prognostic implication.
Authors’ contribution
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Acknowledgments
Introduction Human Epidermal Receptor 2 (HER2), a member of the epidermal growth factor family, is overexpressed in epithelial-derived tumors (Slamon et al., 1987). Studies have shown that the expression of HER2 in gastric cancer tends to predict poor prognosis and a high degree of malignancy (Begnami et al., 2011). Targeting HER2 by blocking HER2-dependent activation of the PI3K/Akt and MAPK/ERK1/2 pathways (Yokoyama et al., 2006) has resulted in tumor growth inhibition in vivo. Therefore, HER2 has emerged as a promising target for antibody therapies. Trastuzumab can specifically bind to HER2 and block the activation of its downstream signaling pathways, which exert a significant effect in HER2-overexpressing breast and gastric cancers (Bang et al., 2010). However, drug resistance has hampered the long-term efficacy of targeted therapy, leading to an urgent need for more modifications and combinations of targeted therapy.