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Differential expression of hormonal and growth factor receptors in salivary duct carcinomas: biologic significance and potential role in therapeutic stratification of patients.

Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
American Journal of Surgical Pathology (Impact Factor: 4.59). 11/2007; 31(11):1645-52. DOI: 10.1097/PAS.0b013e3180caa099
Source: PubMed

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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    • "The incidence of cervical lymph node metastasis is greater in SDC to other parotid malignancies, approximately two thirds of SDC patients present at T3 or T4 stage [4]. The prognosis of SDC is poor with less than 60% five year survival [6] [7], the factors considerable regarding prognosis are advanced clinical presentation, resection margin positivity [8] and HER2/neu positivity [4]. The current case reported at an advanced stage with multiple cervical lymph nodal metastases, lymphovascular emboli, extension to skull base and internal jugular vein, however, absence of perineural spread, intact facial nerve function, adequate tumor free resection margins and negative status of HER2/neu were favorable indicators. "
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    ABSTRACT: Salivary duct carcinoma (SDC) is very rare, only 1–3% of all salivary gland tumors are reported as SDC. SDC predominantly occurs in elderly males, characterized by very aggressive clinical course of the disease with less than 60% five years survival from the day of initial diagnosis, lymph node metastasis and facial nerve involvement is common, the current literature lacks protocol regarding management of this entity and the advantage of adjuvant therapy has not been evaluated due to its rarity in occurrence.
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    • "It is concluded that sex steroids may affect SS and focal adenitis also via their effects on immune cells. Apart from the above mentioned SS, examples of runaway diseases caused by pathological effects of sex steroids on salivary gland cells are seen in many different types of salivary gland cancers that have been shown to carry androgen or estrogen receptors and ⁄ or to be regulated by sex steroids or sex steroid depletion (Nasser et al, 2003; Williams et al, 2007; Sygut et al, 2008). ARs can be used for the classification of some tumors and in the treatment of these diseases in particular androgen deprivation treatments appear promising so that partial or complete remissions of parotid gland carcinoma have been reported (van der Hulst et al, 1994; Locati et al, 2003). "
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    ABSTRACT: Usually no distinction is made between female and male salivary glands although cyclic changes of and ⁄ or differences in serum and salivary sex steroid concentrations characterize women and men. Moreover, sexual dimorphism is well recognized in salivary glands of rodents.Salivary glands contain estrogen and androgen receptors and are, according to modern high throughput technologies,subjected to gender differences not explainable by gene dose effects by the X chromosome alone. Because sex steroids are lipophilic, it is often thought that approximately 10% of them passively diffuse from plasma to saliva. Indeed, saliva can find use as sample material in sports medicine, pediatrics, veterinary medicine and behavioral sciences. Last but not least, humans and other primates are unique in that they have a reticular zone in their adrenal cortex, which produces dehydroepiandrosterone and androstendione pro-hormones. These are processed in peripheral tissues, not only in female breast and uterus and male prostate, but also in salivary glands by an intracrine enzymatic machinery to active 17b-estradiol,dihydrotestosterone and others, to satisfy and buffer against a constantly changing needs caused by circadian,menstrual, pregnancy and chronobiological hormonal changes in the systemic circulation. Female dominance of Sjögren's syndrome and certain forms of salivary gland cancer probably reflect these gender-based differences.
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