HER‐2/<i>neu</i> gene amplification in carcinoma ex pleomorphic adenoma in relation to progression and prognosis: a chromogenic <i>in‐situ</i> hybridization study

Hashimoto, Kazuki; Yamamoto, Hidetaka; Shiratsuchi, Hideki; Nakashima, Torahiko; Tamiya, Sadafumi; Nishiyama, Ken Ichi; Higaki, Yasuki; Komune, Shizuo; Tsuneyoshi, Masazumi; Oda, Yoshinao

doi:10.1111/j.1365-2559.2012.04201.x

Cited by 53 publications

(38 citation statements)

References 35 publications

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“…One carcinoma with both genes amplified was metastatic, though the preceding benign tumour revealed no amplification of HER-2 nor c-myc oncogenes. Some researchers suggest that HER-2 plays a role in the progression of carcinoma ex PA, and that the presence of HER-2 amplification might be an indicator of poor prognosis, which is corroborated by the present study (34).…”

Section: Discussionsupporting

confidence: 79%

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

Nikolic¹,

Aničić²,

Tepavčević³

et al. 2013

Journal of Medical Biochemistry

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Summary Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomor- phic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce. Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detec- tion). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes). Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p<0.001). Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c- myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter poly- morphisms represent susceptibility factors for the develop- ment of PAs in the Serbian population.

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Section: Discussionsupporting

confidence: 79%

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

Nikolic¹,

Aničić²,

Tepavčević³

et al. 2013

Journal of Medical Biochemistry

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“…Strong androgen receptor protein expression has been reported in 40% to 86% of salivary duct carcinoma cases, whereas HER2 protein overexpression and gene amplification have been reported in 17% to 44% and 12% to 52% of samples analyzed, respectively . Although the genomics of CEPA are less well defined, several studies have reported HER2 protein expression and gene amplification in CEPA at frequencies comparable to those seen in salivary duct carcinoma; HER2 overexpression has been suggested as a marker of malignant transformation of pleomorphic adenoma to CEPA . In both CEPA and salivary duct carcinoma, high concordance between HER2 amplification and strong protein expression has generally been reported .…”

Section: Discussionmentioning

confidence: 99%

“…Although the genomics of CEPA are less well defined, several studies have reported HER2 protein expression and gene amplification in CEPA at frequencies comparable to those seen in salivary duct carcinoma; HER2 overexpression has been suggested as a marker of malignant transformation of pleomorphic adenoma to CEPA . In both CEPA and salivary duct carcinoma, high concordance between HER2 amplification and strong protein expression has generally been reported . Among the subtypes of salivary gland cancer, HER2 overexpression has been identified most commonly in salivary duct carcinoma and CEPA, less frequently in adenocarcinoma NOS and mucoepidermoid carcinoma, and rarely in other subtypes, such as ACC .…”

Section: Discussionmentioning

confidence: 99%

Significant and durable clinical benefit from trastuzumab in 2 patients with HER2‐amplified salivary gland cancer and a review of the literature

Thorpe¹,

Schrock²,

Erlich³

et al. 2016

Head & Neck

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“…The increasing frequency of HER2 gene amplification increases with CXPA progression, suggesting that HER2 may play a key role in the progression of this tumor [17]. HER2 , which encodes the 185-kDa transmembrane glycoprotein with tyrosine kinase activity, is considered to play an important role in controlling cell growth and development.…”

Section: Discussionmentioning

confidence: 99%

Complete Response to Trastuzumab-Based Chemotherapy in a Patient with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Salivary Duct Carcinoma ex Pleomorphic Adenoma

Kadowaki¹,

Yatabe

Hirakawa

et al. 2013

Case Rep Oncol

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Introduction: Carcinoma ex pleomorphic adenoma (CXPA) of the salivary glands has often a salivary duct carcinoma (SDC) component, which resembles ductal carcinoma of the breast and frequently overexpresses human epidermal growth factor receptor-2 (HER2). We report a case of metastatic CXPA with SDC component who was treated with trastuzumab-based chemotherapy and has had a durable complete response. Case Report: A 74-year-old man was diagnosed with CXPA of the right parotid gland. The resected tumor was histologically diagnosed as CXPA with a predominant SDC component that showed strong positivity for HER2 protein and HER2 gene amplification. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with paclitaxel and trastuzumab was initiated. A complete response was confirmed after 7 treatment cycles, and no evidence of disease progression has been observed after 13 months of initiation of therapy. Conclusions: This report suggests a potential utility of trastuzumab-based chemotherapy for HER2-positive CXPA.

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HER‐2/neu gene amplification in carcinoma ex pleomorphic adenoma in relation to progression and prognosis: a chromogenic in‐situ hybridization study

Abstract: These results suggest that HER2 may play an important role in the progression of CXPA, and that HER2 amplification may be an additional prognostic indicator of CXPA.

Cited by 53 publications

References 35 publications

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

Significant and durable clinical benefit from trastuzumab in 2 patients with HER2‐amplified salivary gland cancer and a review of the literature

Complete Response to Trastuzumab-Based Chemotherapy in a Patient with Human Epidermal Growth Factor Receptor-2-Positive Metastatic Salivary Duct Carcinoma ex Pleomorphic Adenoma

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