| 1. |
- Fehr, Andre, et al.
(författare)
-
Molecular Characterization of Salivary Gland Carcinomas
- 2019
-
Ingår i: In: Salivary Gland Cancer. 1 ed. Licitra L, Locati L, editors.. - Basel, Switzerland : Springer Nature Switzerland AG. ; , s. 17-32
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The recently updated WHO classification of head and neck tumors has listed more than 20 (sub-)types of salivary gland cancers. Although there was consensus of the Board that diagnosis on histological criteria alone may be inaccurate, the editors finally reasoned that the necessary set up for molecular analyses is not globally available, as yet, or the data are either not convincing or robust enough to supplement the histological and immunohistochemical diagnostic tools. Nevertheless, the increasing knowledge about tumor-type specific translocations, point mutations, and amplifications in salivary gland cancers needs more explanatory comments than the new WHO fascicle could afford, particularly taking into account the already established molecular support of diagnostic, and predictive pathology in specialized clinical centers. In the German Salivary Gland Expert Network (www.hansepathnet.de), we advocate the application of molecular analyses for clinicopathological purposes in mucoepidermoid, adenoid cystic, and secretory carcinomas, while more translational research is necessary before molecular tools can be applied in other neoplasias covered in this chapter, in routine clinical practice.
|
|
| 2. |
- Boecker, W., et al.
(författare)
-
Cellular organization and histogenesis of adenosquamous carcinoma of the pancreas: evidence supporting the squamous metaplasia concept.
- 2020
-
Ingår i: Histochemistry and Cell Biology. - : Springer Science and Business Media LLC. - 0948-6143 .- 1432-119X. ; 154:1, s. 97-105
-
Tidskriftsartikel (refereegranskat)abstract
- Adenosquamous carcinoma of the pancreas (ASCAP) is characterized by conventional pancreatic ductal adenocarcinoma (PDAC) and squamous carcinoma components with at least 30% of the tumour showing squamous differentiation. To get further insight into the histogenesis of these lesions, we analysed the cellular organization of ASCAP compared to PDACs. Using Immunohistochemistry and triple immunofluorescence labelling studies for keratins, p63, p40, MUC1, MUC2, MUC5AC, Ki67, and EGFR we demonstrate that many ASCAPs contain a transitional zone between the K8/18-positive adenocarcinomatous component and the p63+/p40+/K5/K14+squamous component initiated by the expression of p63 in K8/18+adenocarcinomatous cells and the appearance of basally located p63+K5/14+cells. p63+K5/14+cells give rise to fully developed squamous differentiation. Notably, 25% of conventional PDACs without histologically recognizable squamous component contain foci of p63+p40+and K5/14+cells similar to the transitional zone. Our data provide evidence that the squamous carcinoma components of ASCAPs originate from pre-existing PDAC via transdifferentiation of keratin K8/18-positive glandular cells to p63-, p40-, and keratin K5/14-positive squamous carcinoma cells supporting the squamous metaplasia hypothesis. Thus our findings provide new evidence about the cellular process behind squamous differentiation in ASCAPs.
|
|
| 3. |
- Fehr, Andre, et al.
(författare)
-
A closer look at Warthin tumors and the t(11;19).
- 2008
-
Ingår i: Cancer genetics and cytogenetics. - : Elsevier BV. - 0165-4608. ; 180:2, s. 135-9
-
Tidskriftsartikel (refereegranskat)abstract
- The translocation t(11;19)(q21;p13) has been described in mucoepidermoid carcinoma (MEC) and rarely in Warthin tumors (WT), both tumors of the salivary gland. The translocation creates a fusion gene in which exon 1 of CRTC1 is linked to exons 2-5 of MAML2. To verify the translocation in WT, we performed nested reverse transcriptase-polymerase chain reaction using RNA from 48 WTs. This revealed the t(11;19)(q21;p13) translocation and expression of the chimeric gene in two metaplastic WT samples, but in none of the remaining ordinary 46 WTs. On review, the two positive cases were classified as tumors highly suspect for MEC. Indeed, our experience and published observations of the t(11;19)(q21;p13) translocation in WT reveal that only a small subset of WTs are positive, and that these tumors are often classified as infarcted or metaplastic WT, known to overlap considerably with MEC on purely morphological grounds. We therefore conclude that the presence of the t(11;19)(q21;p13) rearrangement favors a diagnosis of MEC.
|
|
| 4. |
- Fehr, Andre, et al.
(författare)
-
A link between the expression of the stem cell marker HMGA2, grading, and the fusion CRTC1-MAML2 in mucoepidermoid carcinoma.
- 2009
-
Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 48:9, s. 777-85
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, the concept of cancer stem cells and their expression of embryonic stem cell markers has gained considerable experimental support. In this study, we examined the expression of one such marker, the high-mobility group AT-hook 2 gene (HMGA2) mRNA, in 53 formalin-fixed, paraffin-embedded mucoepidermoid carcinomas (MEC) and four normal parotid tissues using quantitative real-time RT-PCR (qPCR). MECs are often characterized by the fusion gene CRTC1-MAML2, the detection of which is an important tool for the diagnosis and prognosis of MEC. For detection of the CRTC1-MAML2 fusion transcript, we performed RT-PCR. The mean expression level of HMGA2 was higher in fusion negative (302.8 +/- 124.4; n = 14) than in positive tumors (67.3 +/- 13.1; n = 39). Furthermore, the fusion-negative tumors were often high-grade tumors and the HMGA2 expression level rose with the tumor grade (low: 43.7 +/- 11.0, intermediate: 126.2 +/- 28.3, and high: 271.2 +/- 126.5). A significant difference was found in the HMGA2 expression levels between the different grading groups (one-way ANOVA, P = 0.04) and among the fusion-negative and -positive tumors (t-test, P = 0.05), indicating that the expression level of HMGA2 was closely linked to grading, the presence/absence of the CRTC1-MAML2 fusion, and the tumor behavior of MECs. These findings offer further evidence for the theory that the MEC group comprises two subgroups: one group with the CRTC1-MAML2 fusion, which is a group with a moderate aggressiveness and prognosis, and the other group lacking that fusion corresponding to an increased stemness, and thus, higher aggressiveness and worse prognosis.
|
|
| 5. |
- Fehr, Andre, et al.
(författare)
-
A new type of MAML2 fusion in mucoepidermoid carcinoma.
- 2008
-
Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 47:3, s. 203-6
-
Tidskriftsartikel (refereegranskat)abstract
- The present study reports for the first time a CRTC3-MAML2 fusion gene in a mucoepidermoid carcinoma, as determined by RT-PCR and sequencing. We screened a total of 67 formalin-fixed, paraffin-embedded mucoepidermoid carcinomas for the presence of chimeric genes. In one of these samples, a CRTC3-MAML2 fusion gene was detected. Thus, this report demonstrates the existence of a fusion of MAML2 with CREB regulated transcriptional coactivator CRTC3 additional to the already known fusion of MAML2 and CRTC1. Both gene fusions seem to result in an identical tumor phenotype and the fusion genes CRTC1-MAML2 and CRTC3-MAML2 may play a similar role in the development of mucoepidermoid carcinomas.
|
|
| 6. |
|
|
