Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs)

Locati, Laura D.; Perrone, Francesco; Losa, Marco; Mela, Micol; Casieri, Paola; Orsenigo, Marta; Cortelazzi, Barbara; Negri, Tiziana; Tamborini, Elena; Quattrone, Pasquale; Bossi, Paolo; Rinaldi, Gaetana; Bergamini, Cristiana; Calderone, Rosa Gioia; Liberatoscioli, C.; Licitra, Lisa

doi:10.1016/j.oraloncology.2009.05.635

Cited by 143 publications

(120 citation statements)

References 30 publications

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“…Most of the drugs currently in trials were selected based on observations from preclinical studies initiated before the elucidation of ACC genome (Table 1). For example, the finding that 65% to 90% of ACCs overexpress c‐KIT (CD117), a known oncoprotein, suggested that this receptor would be an appropriate therapeutic target 21, 65, 66. Imatinib, a c‐KIT inhibitor, produces high rates of responses in gastrointestinal stromal tumors with mutant forms of c‐KIT.…”

Section: Introductionmentioning

confidence: 99%

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Chakraborty²,

et al. 2015

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BackgroundAdenoid cystic carcinoma (ACC) is a rare tumor of secretory glands. In this study, recent advances in molecular characterization and in therapeutics are reviewed.MethodsA search of articles in PubMed and of abstracts from national meetings was performed regarding ACC.ResultsRecent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published that may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare.ConclusionACCs have a characteristic chromosomal translocation, but also frequently pick up additional mutations. Clinical research is limited by the rarity and slow growth of ACC. Several ongoing trials are testing agents that inhibit fibroblast growth factor receptor signaling or other signaling pathways. Novel treatments based on the recently sequenced tumor genome are under development. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. 38: 620–627, 2016

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Section: Introductionmentioning

confidence: 99%

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Chakraborty²,

et al. 2015

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“…[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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“…3 Importantly, salivary gland cancer accounts for 3-5% of total head and neck cancer 4,5 and of wide histological and biological diversity. 6 SGT could be benign and malignant type. The chances for malignant transformation of benign SGT vary from 1.9% to 23.3% which is a concern for oncologist all over the world.…”

Section: Introductionmentioning

confidence: 99%

Sperm associated antigen 9(SPAG9) expression and humoral response in benign and malignant salivary gland tumors

et al. 2014

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Keywords: biomarker, cancer testis antigen, early detection and diagnosis, immunotherapeutic target, SPAG9Salivary gland cancers are highly aggressive epithelial tumor associated with metastatic potential and high mortality. The tumors are biologically diverse and are of various histotypes. Besides, the detection and diagnosis is a major problem of salivary gland cancer for available treatment modalities. In the present study, we have investigated the association of sperm associated antigen 9 (SPAG9) expression with salivary gland tumor (SGT). Clinical specimens of benign (n D 16) and malignant tumors (n D 86) were examined for the SPAG9 expression. In addition, the sera and adjacent non-cancerous tissues (n D 72) from available patients were obtained. Our in situ RNA hybridization and immunohistochemistry (IHC) analysis revealed significant difference (p D 0.0001) in SPAG9 gene and protein expression in benign (63%) and malignant tumor (84%) specimens. Further, significant association was also observed between SPAG9 expression and malignant tumors (P D 0.05). A cut-off value of >10% cells expressing SPAG9 protein designated as positive in IHC, predicted presence of malignant SGT with 83.72% sensitivity, 100% specificity, 100% PPV and 83.72% NPV. Humoral response against SPAG9 protein was generated in 68% of SGT patients. A cut-off value of 0.212 OD for anti-SPAG9 antibodies in ELISA predicted presence of malignant SGT with 69.23% sensitivity, 100% specificity, 100% PPV and 78.94% NPV. Collectively, our data suggests that the majority of SGT show significant difference and association among benign and malignant tumors for SPAG9 gene and protein expression and also exhibit humoral response against SPAG9 protein. Hence, SPAG9 may be developed as a biomarker for detection and diagnosis of salivary gland tumors.

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Treatment relevant target immunophenotyping of 139 salivary gland carcinomas (SGCs)

Cited by 143 publications

References 30 publications

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

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

Sperm associated antigen 9(SPAG9) expression and humoral response in benign and malignant salivary gland tumors

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