Differential expression of hormonal and growth factor receptors in salivary duct carcinomas: biologic significance and potential role in therapeutic stratification of patients.
ABSTRACT Salivary duct carcinoma (SDC), a rare malignancy, manifests remarkable morphologic and biologic resemblance to high-grade mammary ductal carcinoma. We contend that, similar to mammary ductal carcinoma, hormones and growth factors may play a role in SDCs. Our aim was to determine the incidence and clinical significance of the expression of several hormone and growth factor receptors and evaluate their potential in therapeutic stratification of SDC patients in the largest cohort studied to date. Eighty-four archived tumor tissue blocks were analyzed immunohistochemically for expression of estrogen receptor-beta (ERbeta), androgen receptor (AR), and proline, glutamic acid, and leucine-rich protein-1 and growth factor receptors HER-2 and epidermal growth factor receptor. The results were correlated with available pathologic, demographic, and clinical data from 59 of 84 cases. Proline, glutamic acid, and leucine-rich protein-1, ERbeta, and AR were expressed individually in 94% (71/76), 73% (57/80), and 67% (56/84) of SDCs, respectively, and coexpressed in 45% (34/75). AR was expressed significantly more often in SDCs of men than in SDCs of women [79% (35/57) vs. 33% (9/27), P<0.001]. Epidermal growth factor receptor and HER-2 were overexpressed individually in 48% (40/83) and 25% (21/84), respectively, and co-overexpressed in 12% (10/83). Survival decreased significantly in patients with lymph node metastasis (P=0.002) and positive surgical margins (P=0.006). Lack of ERbeta expression correlated with increased local and regional recurrence (P=0.05 and P=0.002, respectively). Together, these results indicate that (a) ERbeta down-regulation is associated with adverse clinical features, (b) lymph node and surgical margin status are significant survival factors, and (c) the differential expression of these hormones and growth factor receptors may assist in triaging patients with SDC for novel therapies.
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ABSTRACT: We reviewed treatment outcomes and prognostic factors for patients with salivary ductal carcinoma (SDC) treated with surgery and postoperative radiotherapy from 2005 to 2012.09/2014; 32(3):125-31. DOI:10.3857/roj.2014.32.3.125
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ABSTRACT: Background Salivary ductal carcinoma is a rare cancer with poor prognosis and limited treatment options. Human epidermal receptor 2 (HER2)-directed treatment has been attempted in HER2-amplified or overexpressed salivary gland malignancies with limited success. Methods We report resolution of measurable disease and minimal residual disease in a patient with salivary duct cancer treated with trastuzumab, lapatinib, and bevacizumab, with treatment ongoing for more than 2 years. ResultsThis treatment has been tolerated well except for grade 2 diarrhea and mucositis, which required a dose reduction of lapatinib to 1000 mg daily. The response observed was achieved in spite of receiving extensive prior therapy, including trastuzumab and/or chemotherapy for 20 months on which his tumors progressed. Conclusion The combination of trastuzumab, lapatinib, and bevacizumab may warrant investigation as a non-cytotoxic alternative for treatment of HER2-amplified or overexpressed salivary duct carcinoma and other HER2-amplified or overexpressed salivary gland tumors, particularly those not responsive to trastuzumab monotherapy. © 2013 Wiley Periodicals, Inc. Head Neck 36: E25–E27, 2014Head & Neck 03/2014; 36(3). DOI:10.1002/hed.23429 · 2.83 Impact Factor
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ABSTRACT: Despite the fact that numerous researches have been carried out to prevent head and neck cancer (HNC) and treat those patients, there is no reduction in morbidity rate because the underlying molecular pathogenesis is still poorly understood. Endocrine microenvironment is another vital factor besides other traditional risk factors like tobacco smoking, infections, and alcohol. It has been proven that sex hormone receptors are also expressed in larynx and lungs, in addition to sex organs. Sex hormones play a vital role in gene expression involved in the plethora of biological and neoplastic processes. The role of sex hormones in HNC is still divisive and very few researches have been conducted to describe their role. So, this article is an effort to attract the attention of researchers, endocrinologists, pathologists, and clinicians toward the impending role of sex hormones, with special emphasis on progesterone, estrogen, and prolactin in HNC onset and progression, along with their therapeutic role.11/2014; 4(Suppl 1):S1-S4. DOI:10.4103/2231-0762.144557