Expression of HER‐2/<i>neu</i> gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in‐situ hybridization and immunohistochemistry

Skálová, Alena; Stárek, Ivo; Vaněček, Tomáš; Kučerová, V.; Plank, L; Szépe, P; Palma, Silvia; Leivo, Ilmo

doi:10.1046/j.1365-2559.2003.01600.x

Cited by 161 publications

(103 citation statements)

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“…Only in one tumor specimen was the overexpression linked to a gene amplification. These observations are in concordance with a recent study by Etges et al 30 It is noteworthy that patients negative for HER-2/neu expression clinically also had an unfavorable prognosis, an observation that was reported recently by Skalova et al 31 for a small study group.…”

Section: Table 4 Prognostically Significant Factors In Sdc Clinical Csupporting

confidence: 93%

Clinical and immunohistologic typing of salivary duct carcinoma

Jaehne

Roeser

Jaekel

et al. 2005

Cancer

295

346

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BACKGROUNDDue to the low incidence of salivary duct carcinoma (SDC), only limited data in regard to the biologic behavior of this tumor and its immunohistochemical characteristics are available. The authors analyzed the clinical, molecular, and genetic profile of SDC and identified prognostic factors.METHODSThe follow‐up of 50 patients with SDC was obtained and paraffin‐embedded tumor samples were examined immunohistochemically. In all samples, the expression of Ki‐67, HER‐2, and the oncoproteins p16 and p53 was examined immunohistochemically, followed by a mutation analysis of p16 and p53. The survival rate was calculated by the Kaplan–Meier method and prognostic variables were analyzed with the log‐rank test.RESULTSSDC predominantly effected male patients (66%) in their 7th decade of life. SDC mainly occurred in the parotid gland (78%; submandibular gland, 12%; minor salivary glands, 10%). Approximately two‐thirds of the patients (33 of 50) presented with a T3/T4 tumor. In 28 patients (56%), cervical lymph node metastasis was present at the time of diagnosis. Local disease recurrence was observed in 48% of patients an average of 17.4 months after initial treatment. Distant disease metastasis developed in 48% of patients an average of 29 months after initial treatment. The average overall survival period was 56.2 months. In the current study, 20.6% of the probes with positive HER‐2/neu expression were (+++) positive. p53 was expressed in 83.9% of the tumor samples. In 11.8% of the tumor samples, there was a lack of p16 expression.CONCLUSIONSMutations of the p53 gene were more frequent in tumor samples with (++) and (+++) immunoreactivity and mainly affected exons 7 and 8. A mutation of the p16 gene was only found in 1 tumor sample. Expression of HER‐2/neu and p53 was statistically linked (P < 0.05) to early local disease recurrence, distant disease metastasis, and survival rates. Cancer 2005. © 2005 American Cancer Society.

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Section: Table 4 Prognostically Significant Factors In Sdc Clinical Csupporting

confidence: 93%

Clinical and immunohistologic typing of salivary duct carcinoma

Jaehne

Roeser

Jaekel

et al. 2005

Cancer

295

346

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“…A number of previous studies demonstrated that HER-2/neu and p53 expression are statistically associated with SDC survival rates (3,(15)(16)(17)(18)(19)(20). However, in the present study, the protein expression levels of HER-2/neu, AR, Ki-67, p16 and p53 did not correlate with prognosis, although HER-2/neu, AR and p16 demonstrated a positive expression rate of >50%, which may contribute to the diagnosis for SDC.…”

Section: A B C D Econtrasting

confidence: 80%

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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“…The HER2 gene encodes for a receptor tyrosine kinase often amplified and overexpressed in SDC (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Using FISH, we detected HER2 gene amplification in 8 of 27 cases (30%).…”

Section: Clinical Characteristics Of the Cohortmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17]. In contrast to breast carcinoma, SDC are consistently negative for estrogen-a and progesterone receptors, whereas the expression of androgen receptor (AR) is observed in the majority of cases (18).…”

Section: Introductionmentioning

confidence: 99%

Detection of Novel Actionable Genetic Changes in Salivary Duct Carcinoma Helps Direct Patient Treatment

Nardi

Sadow

Juric

et al. 2013

Clinical Cancer Research

105

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Purpose: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland cancers for which cytotoxic chemotherapy has limited efficacy. We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents.Experimental Design: We genotyped 27 SDC archival specimens from patients followed at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2011. These included the tumors of 8 patients who were tested prospectively. Targeted mutational analysis of 13 clinically relevant cancer genes was conducted using SNaPshot multiplexed genotyping. FISH was conducted to detect HER2 gene amplification. Patient medical records and tumor histopathologic features were retrospectively reviewed.Results: Mutually exclusive genetic aberrations were detected in 15 of 27 (56%) tumors, including 2 (7%) mutations in BRAF, 5 (19%) mutations in PIK3CA, and 8 (30%) cases of HER2 gene amplification. To our knowledge, this is the first time that BRAF and PIK3CA mutations have been reported in this tumor type. Prospective clinical testing of 8 patients with SDC identified actionable genetic alterations in 6 tumors and influenced therapeutic decisions for all 6 patients.Conclusion: SNaPshot molecular profiling identified novel genetic changes in SDCs, expanded the therapeutic options for patients with this rare tumor, and is changing SDC management at our institution. These findings highlight the importance of using broad-based genetic profiling to expedite the identification of effective-targeted therapies for patients with rare malignancies. Clin Cancer Res; 19(2); 480-90. Ó2012 AACR.

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Expression of HER‐2/neu gene and protein in salivary duct carcinomas of parotid gland as revealed by fluorescence in‐situ hybridization and immunohistochemistry

Cited by 161 publications

References 37 publications

Clinical and immunohistologic typing of salivary duct carcinoma

Clinical and immunohistologic typing of salivary duct carcinoma

Salivary duct carcinoma: A clinopathological report of 11 cases

Detection of Novel Actionable Genetic Changes in Salivary Duct Carcinoma Helps Direct Patient Treatment

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