Amplification and Overexpression of HER2/neu Gene and HER2/neu Protein in Salivary Duct Carcinoma of the Parotid Gland

Cornolti, Giorgio; Ungari, Marco; Morassi, Maria Laura; Facchetti, Fabio; Rossi, Elisa; Lombardi, Davide; Nicolai, Piero

doi:10.1001/archotol.133.10.1031

Cited by 92 publications

(72 citation statements)

References 30 publications

(48 reference statements)

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“…Due to the limited efficacy and severe complications of surgery and radiotherapy, a more systematic therapeutic approach should be analyzed in order to improve the prognosis of SDC. The present study demonstrated a high positivity rate for HER-2/neu and AR expression in SDC, indicating that SDC carcinogenesis may resemble that of breast ductal carcinoma or prostate cancer (4,7,11,13,15,18,21,22). As HER-2/neu blockers (trastuzumab) are effective in treating HER-2-overexpressing breast cancer, this agent may be useful for the treatment of SDC.…”

Section: A B C D Esupporting

confidence: 50%

“…Due to the rarity of SDC, little data regarding its clinicopathological characteristics exists. The standard treatment for SDC is surgery in combination with radiotherapy, however, the prognosis of SDC is poor (4)(5)(6)(7). Effective therapeutic strategies rely on a sufficient understanding of SDC and its prognostic factors, therefore, the aim of the present retrospective study was to summarize the clinicopathological characteristics of SDC and to evaluate the current treatment modalities currently used at the Affiliated Hospital of Stomatology of Nanjing University (Nanjing, Jiangsu, China).…”

Section: Introductionmentioning

confidence: 99%

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Salivary duct carcinoma: A clinopathological report of 11 cases

et al. 2015

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Abstract. The aim of the present study was to summarize the clinicopathological and immunohistochemical characteristics of salivary duct carcinoma (SDC) and to evaluate the currently available treatment modalities. Between 2001 and 2011, 11 patients with SDC were diagnosed and treated at the Affiliated Hospital of Stomatology of Nanjing University (Nanjing, Jiangsu, China). The present study retrospectively reviewed the clinicopathological and immunohistochemical data of these 11 patients and the results indicated that the parotid gland was the most commonly affected site, followed by the submandibular gland and the palate. Furthermore, the mean age of onset was 58.8 years and all cases were treated with surgery, with 72.7% receiving post-operative radiation therapy. The range for the follow-up period was 10-89 months and of the 11 patients investigated, only two succumbed to the disease. In addition, the two-year overall survival rate was 75% according to Kaplan-Meier analysis and the mean overall survival time was 72.8 months. In conclusion, the present study determined that the site of the malignancy is the best predictor of survival in patients with the rare salivary malignancy SDC, while age, gender, T stage, N stage, American Joint Committee on Cancer stage, nerve paralysis, post-operative radiation, neck dissection, and protein expression levels of Ki-67, androgen receptor and human epidermal growth factor-2/neu are less influential factors. IntroductionSalivary duct carcinoma (SDC) is a rare type of salivary malignancy which accounts for <10% of all salivary malignancies, and the majority of its histological characteristics are similar to those of mammary duct carcinoma (1-3). SDC exhibits characteristic ductal lesions and tumor cells are often arranged in a 'Roman bridge' formation and cribriform architecture, with comedo necrosis (2). Due to the rarity of SDC, little data regarding its clinicopathological characteristics exists. The standard treatment for SDC is surgery in combination with radiotherapy, however, the prognosis of SDC is poor (4-7). Effective therapeutic strategies rely on a sufficient understanding of SDC and its prognostic factors, therefore, the aim of the present retrospective study was to summarize the clinicopathological characteristics of SDC and to evaluate the current treatment modalities currently used at the Affiliated Hospital of Stomatology of Nanjing University (Nanjing, Jiangsu, China). (2), were identified at the Affiliated Hospital of Stomatology. Subsequent to excluding any patients with distant metastasis or a previous history of head-neck surgery, all 11 patients primarily underwent surgical treatment, predominantly consisting of local extensive resection with neck dissection, followed by post-operative radiation therapy. All cases were followed up from the date of the surgical procedure to the date of mortality or the date patients were lost to follow-up. Clinical and histological data were reviewed (Table I). Patients and methods PatientsStatistical analysis. All d...

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Section: A B C D Esupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Salivary duct carcinoma: A clinopathological report of 11 cases

et al. 2015

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“…Overexpression of HER2 contributes to the pathogenesis of many cancers including breast, ovarian, gastric, and salivary gland cancers [111][112][113][114]. Stephens et al reported mutations in ERBB2 kinase domain in 4% of the tumor samples from patients with lung cancer [115].…”

Section: Erbb2mentioning

confidence: 99%

Genomics of Squamous Cell Lung Cancer

2013

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“…erbB receptors, especially of erbB2, play an important role in carcinoma formation, and its dysfunction promotes tumourigenesis. Overexpression of the erbB2 gene was frequently observed in human tumours, including those of breast, lung, stomach, and oral cavity (25)(26)(27). Capable of stable and highly specific silencing of gene expression, siRNAs have been extensively applied to silence abnormal gene expression in the treatment of cancer (28).…”

Section: Discussionmentioning

confidence: 99%

erbB2 gene silencing and its effect on PTEN in SACC-83 salivary adenoid cystic carcinoma cells

Liu

Zhang²,

Ren³

et al. 2010

Oncol Rep

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Abstract. erbB2 gene plays an important role in carcinoma formation. erbB2 overexpression was observed in many types of tumours, including salivary carcinoma. However, a putative erbB2 and PTEN interaction remains largely unknown in salivary adenoid cystic carcinoma cells. The purpose of this study was to silence erbB2 gene and investigate the functional relationship between erbB2 and PTEN in SACC-83 salivary adenoid cystic carcinoma cells. erbB2-specific siRNAs were transfected into SACC-83 cells using cationic liposome. RT-PCR, immunocytochemistry and Western blotting were employed to detect erbB2 and PTEN expression. Compared with the control groups, erbB2 mRNA expression was decreased in the erbB2-siRNA transfection group, and immunocytochemistry and Western blotting indicated a concordant erbB2 protein reduction. The average optical density values for erbB2 proteins in erbB2-siRNA transfected group were significantly lower than that in the control groups (P<0.05). On the other hand, PTEN expression at both mRNA and protein levels were not significantly affected by erbB2 silencing (P>0.05). In conclusion, the data indicate that siRNA could effectively silence erbB2 gene expression in SACC-83 cells, but PTEN expression appeared unaltered following erbB2 silencing. PTEN expression might not be strictly associated with erbB2 amplification in SACC-83 cells. Future studies will more closely examine the molecular and biological relationships of erbB2 and PTEN in salivary adenoid cystic carcinoma. IntroductionSalivary adenoid cystic carcinoma (SACC) is a common oral tumour, known to be highly destructive and unpredictable (1-3). Previous research has demonstrated a possible role of oncogenic activation in SACC (4-6). erbB2, also called HER2, is a cell surface receptor tyrosine kinase (RTK) and becomes internalized upon ligand binding which can trigger a multitude of signaling pathways, such as MAPKs and PI3K. The erbB family consists of four structurally related tyrosine kinase receptors: erbB1, erbB2, erbB3, and erbB4. These four receptors contain multiple cytosolic tyrosines, which can interact with one or more adaptor proteins to activate downstream signaling pathways when phosphorylated. Furthermore, the erbB receptors display functional redundancy with overlapping signaling pathways. erbB2 is the preferred heterodimerization partner of all erbB proteins, and plays important roles in the lateral transmission of signals between other erbB receptors (7). Consequently, erbB2 has been shown to trigger signal transduction leading to cell growth and differentiation. Tumours showing erbB2 amplification/ overexpression have been shown to demonstrate increased aggressiveness and metastatic potential and decreased overall survival (8-10). In previous studies, erbB2 gene expression was found to be elevated in many types of tumours, including salivary gland carcinoma (11-13).PTEN is an important tumour suppressor gene located on chromosome 10q23.3. The encoded protein displays homology with the catalytic domain of tyrosine...

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Amplification and Overexpression of HER2/neu Gene and HER2/neu Protein in Salivary Duct Carcinoma of the Parotid Gland

Abstract: Objectives: To detect amplification of the HER2/neu gene by means of fluorescence in situ hybridization (FISH) in a series of 13 salivary duct carcinomas (SDCs) and to compare the results with immunohistochemical (IHC) assessment of HER2/neu protein expression.

Cited by 92 publications

References 30 publications

Salivary duct carcinoma: A clinopathological report of 11 cases

Salivary duct carcinoma: A clinopathological report of 11 cases

Genomics of Squamous Cell Lung Cancer

erbB2 gene silencing and its effect on PTEN in SACC-83 salivary adenoid cystic carcinoma cells

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