Differential Expression of Hormonal and Growth Factor Receptors in Salivary Duct Carcinomas

Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
American Journal of Surgical Pathology (Impact Factor: 5.15). 11/2007; 31(11):1645-52. DOI: 10.1097/PAS.0b013e3180caa099
Source: PubMed


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: Introduction: 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, SCD is characterized by an 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 rare occurrence. Presentation of case: We report patient with stage IV HER2/neu negative SDC successfully treated with surgery followed by adjuvant radiotherapy, patient is followed up for 40 months without evidence of recurrence or metastasis. Discussion: SDC is reported to be similar to mammary duct carcinoma in clinical and immunohistologic typing, further it shows an association of expression of HER-2/neu and p53, with early local disease recurrence, distant metastasis and survival, however; current case was adequately followed up and reevaluated after 26 months, MRI did not show evidence of recurrence. Conclusion: SDC is a rare tumor and information on association of HER2/neu with survival is useful in further research on this tumor.
    Full-text · Article · Jan 2015 · International Journal of Surgery Case Reports
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    • "An immunohistochemical analysis indicates that AR and GCDFP-15 are highly and specifically expressed in more than 80% and 90% of patients with SDC, respectively, whereas ER and PgR, well known as common breast carcinoma markers, are very weakly or negatively stained [11,20-22]. Actually, one paper proposed that, when the cytologic features of high grade adenocarcinoma with a variety of cell morphology are difficult to make an accurate diagnosis, immunostaining for AR and ER on cytologic smears would be very useful for the diagnosis of SDC [19]. "
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    ABSTRACT: A history of a recent rapid increase in long-standing swelling mass was presented in the right parotid gland of an 85-year-old male. The inadequate cytologic specimens contained few small clusters of three-dimensional malignant epithelial cells having hyperchromatic pleomorphic nuclei and prominent nucleoli, adjacent to a cluster of benign monomorphic myoepithelial cells. We first interpreted it merely as an adenocarcinoma, not otherwise specified. A radical parotidectomy was performed, and gross examination revealed an encapsulated and firm tumor lesion, looking grayish-blue to yellowish-white, focally associated with extracapsular invasion. On microscopic examination, the tumor was predominantly composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, often arranged in a Roman-bridge appearance with foci of comedo necrosis, alternating with extensive infiltration to adjacent stroma in a trabecular or alveolar fashion with severe vessel permeation. Within the background of pleomorphic adenoma, the carcinoma cells sometimes replaced ductal luminal cells while retaining an intact-like myoepithelial layer. Therefore, we finally made a diagnosis of invasive salivary duct carcinoma ex pleomorphic adenoma. We should be aware that owing to its characteristic features, cytopathologists might be able to determine correct diagnosis, based on multiple and adequate samplings. Virtual slides The virtual slide(s) for this article can be found here:
    Full-text · Article · May 2012 · Diagnostic Pathology
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    • "Williams et al. reported that most tumors derived from breast and salivary glands expressed estrogen receptor-beta (ER-β) and that the patients whose tumors lacked ER-β were at higher risk for local recurrence (Williams et al., 2007). In addition, previous studies have linked the loss of ER expression to aggressive features in adenocarcinomas of the breast, prostate, and colon (Foley et al., 2000; Fuqua et al., 2003; Leygue et al., 1999; Maggiolini et al., 2004; Strom et al., 2004; Wong et al., 2005). "

    Full-text · Chapter · Jan 2012
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