Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo‐ and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease‐free survival (DFS), distant metastasis‐free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in‐situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and—to a lesser extent—HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting.
IntroductionHodgkin lymphoma (HL) is characterized by the presence of a malignant cell population consisting of mononucleated Hodgkin cells and multinucleated Reed-Sternberg cells. 1,2 A large variety of secondary molecular aberrations have been defined for HL; however, no HL-specific primary transforming event has been identified. The origin of these cells was elucidated only recently when Küppers et al found that HL cells express rearranged immunoglobulin genes. 3 This indicated that HL cells are of B-cell origin, although they often lack typical B-lineage markers such as CD20, cell surface B-cell receptor (BCR), and CD79a. 1,4 The detection of somatic hypermutations and the presence of crippled immunoglobulin (Ig) 5 indicate that germinal center (GC) B cells are the precursors of HL cells. It is now assumed that GC B cells that escaped negative selection and acquired survival and proliferative advantages are the precursor of HL cells. 2 The B cell-specific transcription program appears to be silenced in HL cells, resulting not only in abolition of Ig gene expression but also in silencing of B cell-specific factors that play essential roles in the GC stages of B cell development and maturation. [6][7][8] The abolition of Ig gene expression may also be caused by epigenetic silencing. 9 Recent evidence has shown that basic helix-loop-helix transcription factor E47, encoded by the E2A gene, which is essential for B-cell development, [10][11][12] is inactivated in HL cells due to a combination of down-regulation of E2A gene expression and up-regulation of the E2A antagonists Id2 and the transcriptional repressor ABF-1. 11 E47 is involved in establishing B-cell identity by regulating expression of a number of B cell-specific proteins and BCR. 10,11 A conspicuous feature of HL cells is the aberrant expression of markers that are specific for cell types other than B cells. For instance, these cells express the myeloid cell marker CD15, 13 the activation marker CD30, 14 and the T-cell lineage transcription factor GATA3. 15 HL cells display constitutively nuclear localization and activation of nuclear factor-B (NF-B). 16,17 The presence of mutations in NFKBIA, the gene encoding IB␣, in 30% of primary Hodgkin lymphomas and NF-B/REL locus amplifications suggests that genetic alterations that lead to continued activation of NF-B play a crucial role in the transformation process of classical HL. 5,18 However, constitutive activation of NF-B can also be observed in other B-cell malignancies, making it unlikely that constitutive activation of NF-B is the sole cause of HL genesis. 19 Other transcription factors that might be involved in HL are the signal transducers of activation and transcription (STAT) proteins. STAT3, 20 STAT5, 21 and STAT6 22 have been shown to be continuously activated in HL cells. A possible role of STATs, in particular STAT3 and STAT5, in genesis of B-cell tumors has generated interest because these factors have been shown to play a role in control of proliferation and differentiation in various stag...
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