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Aims: Myoepithelial salivary gland tumours are uncommon and follow an unpredictable biological course. The aim was to examine their molecular background to acquire a better understanding of their clinical behaviour. Methods and results: Expression of protein (E2F1, p16INK4a, p53, cyclin D1, Ki67 and Polycomb group proteins BMI-1, MEL-18 and EZH2) was investigated in 49 benign and 30 primary malignant myoepithelial tumours and five histologically benign recurrences by immunohistochemistry and the findings correlated with histopathological characteristics. Benign tumours showed a higher percentage of cells with expression of p16INK4a pathway members [p16INK4a and E2F1 (both P < 0.001), and cyclin D1, P = 0.002] compared with normal salivary gland. Furthermore, malignant tumours expressed p53 ( P = 0.003) and EZH2 ( P = 0.09) in a higher percentage. Recurrences displayed more p53 + tumour cells ( P = 0.02) than benign primaries. Amongst the benign tumours, the clear cell type had the highest proliferation fraction ( P = 0.05) and a higher percentage of EZH2 was detected in the plasmacytoid cell type ( P = 0.002). Conclusions: This study is the first to demonstrate that deregulation of the p16INK4a senescence pathway is involved in the development of myoepithelial tumours. We propose that additional inactivation of p53 in malignant primaries and benign recurrences contributes to myoepithelial neoplastic transformation and aggressive tumour growth. [ABSTRACT FROM AUTHOR]

We herein report the asymmetric organocatalytic addition of azlactones to allenoates. Upon using chiral quaternary ammonium salt catalysts, i.e., Maruoka's binaphthyl-based spirocyclic ammonium salts, the addition of various azlactones to allenoates proceeds in a β-selective manner with moderate levels of enantioselectivities (up to 83:17 er). Furthermore, the obtained products can be successfully engaged in nucleophilic ring opening reactions, thus giving highly functionalized α-amino acid derivatives., (Copyright © 2024, Nasiri et al.)

The enantioselective addition of isoxazolidin-5-ones to the β-carbon of allenoates has been carried out by using a novel spirobiindane-based quaternary ammonium salt catalyst. This protocol, which proceeds under classical liquid-solid phase-transfer conditions, gives access to unprecedented highly functionalized β 2,2 -amino acid derivatives with good enantioselectivities and in high yields, and further manipulations of these products have been carried out as well., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

The catalytic use of quaternary ammonium iodides under oxidative conditions allows for the direct conversion of readily available β-ketolactones into dihydrobenzofurans via a decarboxylative oxidative cycloetherification sequence facilitated by an in situ formed ammonium hypoiodite species.

We herein report an asymmetric protocol to access a series of orthogonally functionalized acyclic chiral target molecules containing a quaternary stereogenic center by carrying out the enantioselective α-alkylation of novel orthogonally functionalized dioxolane-containing cyanoacetates under chiral ammonium salt catalysis. By using just 1 mol % of Maruoka's spirocyclic ammonium salt catalysts enantioselectivities up to e.r.=97.5 : 2.5 could be achieved and further functional group manipulations of the products were carried out as well., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

Detailed investigations concerning the organocatalytic (asymmetric) α-azidation of prochiral β-ketoesters were carried out. It was shown that the racemic version of such a reaction can either be carried out under oxidative conditions using TMSN₃ as the azide-source with quaternary ammonium iodides as the catalysts, or by using hypervalent iodine-based electrophilic azide-transfer reagents with different organocatalysts. In addition, the latter strategy could also be carried out with modest enantioselectivities when using simple cinchona alkaloid catalysts, albeit with relatively low yields.

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in the majority of lung cancer. This study aims at defining connections between STAT3 function and the malignant properties of non-small cell lung carcinoma (NSCLC) cells. To address possible mechanisms by which STAT3 influences invasiveness, the expression of matrix metalloproteinase-1 (MMP-1) was analyzed and correlated with the STAT3 activity status. Studies on both surgical biopsies and on lung cancer cell lines revealed a coincidence of STAT3 activation and strong expression of MMP-1. MMP-1 and tyrosine-phosphorylated activated STAT3 were found co-localized in cancer tissues, most pronounced in tumor fronts, and in particular in adenocarcinomas. STAT3 activity was constitutive, although to different degrees, in the lung cancer cell lines investigated. Three cell lines (BEN, KNS62, and A549) were identified in which STAT3 activitation was inducible by Interleukin-6 (IL-6). In A549 cells, STAT3 activity enhanced the level of MMP-1 mRNA and stimulated transcription from the MMP-1 promoter in IL-6-stimulated A549 cells. STAT3 specificity of this effect was confirmed by STAT3 knockdown through RNA interference. Our results link aberrant activity of STAT3 in lung cancer cells to malignant tumor progression through up-regulation of expression of invasiveness-associated MMPs., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Basaloid squamous cell carcinoma is a variant of squamous cell carcinoma, preferentially arising in the head and neck region. Current reports point to an association of basaloid squamous cell carcinoma (BSCC) and human papilloma virus (HPV) infection. This virus is supposed to be an aetiological factor in this entity. The aim of this study was to analyse the HPV infection status in different entities of oral neoplasms or dysplasias with basaloid differentiation of epithelial cells., Materials and Methods: The study comprised data from 34 oral lesions of squamous epithelial origin: 17 BSCCs, 10 papillomas and 7 hyperplasias/dysplasias of oral epithelia. HPV DNA was detected by means of a hybrid capture technique. HPV types were identified by direct sequencing. Immunohistochemical investigation of the specimens with anti-p16 antibody was performed in order to elucidate the putative role of p16 as a surrogate marker of HPV infection., Results: The rate of HPV-infected BSCC was extraordinarily high. About two thirds of the cases (61%, 11/17) were infected with HPV high-risk types, predominantly with HPV genotype 16 (>90%, 10/11). The infection status differed significantly between BSCC and other oral lesions in terms of frequency of HPV infection and HPV genotypes. p16 expression proved not to be a suitable surrogate marker of HPV high-risk infection in oral lesions, in particular in BSCC. This was an essential difference of this collective compared to genital carcinomas with HPV high-risk infections., Conclusion: This study revealed a high association between BSCC and HPV type 16. This close phenotype-genotype correlation could be of diagnostic value. Type-specific analysis of HPV infection in head and neck cancer may be important in the differential diagnosis of malignancies in the head and neck region with a basaloid growth pattern. However, the investigation is technically demanding, including hybridisation and sequencing techniques. A simplified test for HPV in BSCC of the oral cavity using the immunohistochemical proof of p16 expression as a surrogate marker is non-effective.

Introduction: Peripheral giant cell granuloma (GC) of the jaw is a tumour-like lesion, situated on the gingiva. The aim of this study was to: (a) better define the cellular compartments of the lesion and (b) compare the protease expression-profile in GC lesions of the jaws to GC lesions of other sites., Materials and Methods: This study comprised 54 GC lesions (jaws: 30, tendon sheaths: 22, salivary glands: 2). A microarray technique was applied to the study of osteoclast-specific or osteoclast-like features of different sites (CD68, CD51, RANK, M-CSF). Proteases were immunohistochemically identified [cathepsin K, L, S and matrix metalloproteinase 9 (MMP9)]., Results: The GC of all lesions were immunoreactive for CD68 and CD51. Factors indicating the differentiation and activation of osteoclasts were detected in all lesions (RANK, M-CSF, cathepsin K, MMP9). The expression profile of M-CSF in GC and stroma cells was of a medium grade in cases with no apparent destruction of bone, whereas RANK was expressed only weakly in mono- or multinuclear CD68-positive cells., Conclusion: The results of this study reveal an identical cellular composition for all lesions irrespective of site. GC of lesions at all sites contain the same osteolytic proteases and express cytokines that are effective in bone metabolism. The reason for the absence of osteolysis in some 'epulis' cases may be due to the topography of the lesion. Furthermore, the reduced number of binding sites, revealed by the low expression profile of RANK, may possibly be responsible for an absence of or only superficial osteolysis in these cases, despite evidence of M-CSF.

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.

Salivary gland myoepithelial tumors are relatively uncommon tumors with an unpredictable clinical course. More knowledge about their genetic profiles is necessary to identify novel predictors of disease. In this study, we subjected 27 primary tumors (15 myoepitheliomas and 12 myoepithelial carcinomas) to genome-wide microarray-based comparative genomic hybridization (array CGH). We set out to delineate known chromosomal aberrations in more detail and to unravel chromosomal differences between benign myoepitheliomas and myoepithelial carcinomas. Patterns of DNA copy number aberrations were analyzed by unsupervised hierarchical cluster analysis. Both benign and malignant tumors revealed a limited amount of chromosomal alterations (median of 5 and 7.5, respectively). In both tumor groups, high frequency gains (> or =20%) were found mainly at loci of growth factors and growth factor receptors (e.g., PDGF, FGF(R)s, and EGFR). In myoepitheliomas, high frequency losses (> or =20%) were detected at regions of proto-cadherins. Cluster analysis of the array CGH data identified three clusters. Differential copy numbers on chromosome arm 8q and chromosome 17 set the clusters apart. Cluster 1 contained a mixture of the two phenotypes (n = 10), cluster 2 included mostly benign tumors (n = 10), and cluster 3 only contained carcinomas (n = 7). Supervised analysis between malignant and benign tumors revealed a 36 Mbp-region at 8q being more frequently gained in malignant tumors (P = 0.007, FDR = 0.05). This is the first study investigating genomic differences between benign and malignant myoepithelial tumors of the salivary glands at a genomic level. Both unsupervised and supervised analysis of the genomic profiles revealed chromosome arm 8q to be involved in the malignant phenotype of salivary gland myoepitheliomas.

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., ((c) 2007 Wiley-Liss, Inc.)

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.

The high-mobility group protein HMGI(Y) is a member of a family of nonhistone chromosomal proteins, which have been implicated in the regulation of inducible gene transcription, integration of retroviruses into chromosomes, and induction of neoplastic transformation and metastatic progression in cancer cells. The human trophoblast is a tissue that shares proliferation capacity and invasiveness with neoplastic tissues, but in which these processes are tightly regulated. Recently we could show that HMGI(Y) is expressed in the normal human placenta, where it is localized in the nuclei of villous cytotrophoblast, in the anchoring villi at the implantation site and in extravillous (intermediate) trophoblast invading the maternal decidua. In contrast, the majority of the nuclei of the villous syncytiotrophoblast, a terminally differentiated tissue, was negative. The purpose of this study was to investigate the expression pattern of HMGI(Y) in gestational trophoblastic diseases (GTD), which has not been studied so far. To analyze the expression of HMGI(Y), we performed immunohistochemistry on a total of 29 cases of GTD, including 21 hydatidiform moles and 8 choriocarcinomas. Hydatidiform moles showed a positivity for HMGI(Y) in villous cytotrophoblast and in areas of the trophoblast proliferations on the villous surface; villous syncytiotrophoblast was negative. The choriocarcinomas showed strong immunoreactivity in all cases. The expression pattern of HMGI(Y) in gestational trophoblastic diseases indicates that it might play a role in the pathogenesis of GTD and might be potentially useful as an additional diagnostic marker for such lesions.

The t(14;18)(q32;q21) involving the MALT1/MLT and IGH genes has been identified recently as a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. The frequency of secondary chromosomal aberrations in MALT lymphomas harboring the t(14;18) is largely unknown. We therefore analyzed six t(14;18)-positive MALT lymphomas (five parotid, one conjunctiva) by interphase fluorescence in situ hybridization for aneuploidies of chromosomes 3, 7, 12, 18, and X, gains or disruption of the CMYC/8q24 and BCL6/3q27 genes, as well as deletions of the retinoblastoma and TP53 tumor suppressor genes. Except for one MALT lymphoma of the parotid with trisomy 3, neither aneuploidies nor deletions were detected in any of our cases.

Salivary duct carcinomas (SDC) are high grade neoplasms morphologically reminiscent of breast ductal carcinomas. Whereas the latter are well characterized, the body of immunophenotypic and cytogenetic data on SDC is limited. We studied 23 SDC by conventional histology, immunohistology, in situ hybridization, and comparative genomic hybridization (CGH). Data were subjected to biomathematical analysis in comparison to previously characterized breast ductal carcinomas in situ and invasive ductal carcinoma cases. Most SDC stained for cytokeratins (Ck) Ck 8/18 (77 %) or Ck 5/6 (30 %), 30 % of cases expressed the androgen receptor (AR), 14 cases (63 %) expressed c-erbB2, and one case stained for prostate specific antigen. Except for two cases, Ck 8/18 and Ck 5/6 were not coexpressed. Ck 8/18 expression positively correlated with presence of c-erbB2 and AR. At variance, Ck 5/6 correlated positively with p63 and inversely with both AR and c-erbB2 expression. Ck 5/6 and p 63 co-expression was also found in a distinct population of ductal epithelial cells of normal salivary glands. CGH analysis of SDC revealed increasing numbers of alterations in correlation with advanced diseases, but no recurrent alterations. Cluster analysis of phenotypic and genotypic markers assigned both salivary and breast carcinomas to numerous clusters independent of the primary tumour site. Although undistinguishable by conventional histology, SDC are heterogeneous, comprising at least two immunophenotypically distinct subgroups of neoplasms. Cluster analysis suggests several distinct patterns of gene expression common to both primary sites explaining morphologic parallels between SDC and high grade breast cancer.

Chromosome translocations in tumors frequently give rise to fusion genes encoding proteins with oncogenic activities. Mucoepidermoid carcinomas (MEC) are characterized by a t(11;19)(q21-22;p13) translocation found in approximately 60% of the tumors. This t(11;19) translocation results in a fusion gene consisting of exon 1 of the MECT 1 gene and exons 2-5 of the MAML 2 gene. As a result of the t(11;19) a fusion protein is generated which, independent of NOTCH-ligands, activates the transcription of the NOTCH target gene HES 1. The altered function of MAML 2 causes a disruption of NOTCH signalling which suggests a novel mechanism of tumorigenesis. Pending the elucidation of the t(11;19) at the molecular level of an apparently identical chromosomal translocation in Warthin's tumor, the identification of the translocation in MEC by FISH- and/or RT-PCR-analyses may become important in diagnosis and might have prognostic relevance. Warthin's tumors are benign salivary gland neoplasms with a distinctive histomorphology and histogenesis completely different from MEC.

The initiation of angiogenesis, called the angiogenetic switch, is a crucial early step in tumor progression and propagation, ensuring an adequate oxygen supply. The rapid growth of tumors is accompanied by a reduced microvessel density, resulting in chronic hypoxia that often leads to necrotic areas within the tumor. These hypoxic and necrotic regions exhibit increased expression of angiogenetic growth factors, eg, vascular endothelial growth factor, and may also attract macrophages, which are known to produce a number of potent angiogenetic cytokines and growth factors. A group of molecules that may act as mediators of angiogenesis are the so-called high-mobility group proteins. Recent studies showed that HMGB1, known as an architectural chromatin-binding protein, can be extracellularly released by passive diffusion from necrotic cells and activated macrophages. To examine the angiogenetic effects of HMGB1 on endothelial cells an in vitro spheroid model was used. The results of the endothelial-sprouting assay clearly show that exogenous HMGB1 induced endothelial cell migration and sprouting in vitro in a dose-dependent manner. Thus, this is the first report showing strong evidence for HMGB1-induced sprouting of endothelial cells.

Purpose: Analysis of the efficacy of fast neutron radiotherapy in the treatment of adenoid cystic carcinomas (ACC) of the salivary glands, identification of prognostic variables and dedifferentiation after radiotherapy., Patients and Methods: Histological slides of primary and recurrent lesions of 71 patients were reviewed to confirm the diagnosis and to analyse subtypes. Median follow-up was 52 months. Local control rate and overall survival were analysed in multivariate analysis. Complications are also described., Results: Primary vs. recurrent therapy (p=0.001), margin-status (p=0.01) and subtype (p=0.019) influenced overall survival. Primary vs. recurrent therapy (p=0.001), margin-status (p=0.018) and T-stage (p=0.043) influenced local control rate. Dedifferentiation was seen in only 1/17 cases., Conclusion: The calculated prognostic factors illustrate the importance of a radical primary therapy. Histological subtype is a significant additional factor for overall survival and, in case of dedifferentiation, it is a strong predictor of a detrimental outcome.

The recently discovered MLT/MALT1 gene is fused with the API2 gene in the t(11;18)(q21;q21), which characterizes about one-third of MALT lymphomas. In order to screen for variant translocations and amplifications of MLT/MALT1, we have developed a novel, undirected two-color interphase fluorescence in situ hybridization (FISH) assay with two PAC clones flanking MLT/MALT1. This assay was applied to 108 marginal zone B-cell lymphomas (MZBCLs), including 72 extranodal MALT lymphomas, 17 nodal, and 19 splenic MZBCL. In 19 MALT lymphomas (26%), but in none of the nodal or splenic MZBCL, separated hybridization signals of the MLT/MALT1 flanking probes, were found. Further FISH analyses showed that 12 of these 19 cases displayed the classical t(11;18) and the remaining seven cases revealed the novel t(14;18)(q32;q21), involving the MLT/MALT1 and IGH genes. The frequency at which these translocations occurred varied significantly with the primary location of disease. The t(11;18) was mainly detected in gastrointestinal MALT lymphomas, whereas the t(14;18) occurred in MALT lymphomas of the parotid gland and the conjunctiva. Amplification of MLT/MALT1 was not observed in any of the lymphomas analyzed. We conclude that the translocations t(11;18)(q21;q21) and t(14;18)(q21;q32) represent the main structural aberrations involving MLT/MALT1 in MALT lymphomas, whereas true amplifications of MLT/MALT1 occur rarely in MZBCL.

The high-mobility group protein HMGI(Y) is a member of a family of non-histone chromosomal proteins, which have been implicated in the regulation of inducible gene transcription, integration of retroviruses into chromosomes and induction of neoplastic transformation and metastatic progression in cancer cells. The human trophoblast is a tissue that shares proliferation capacity and invasiveness with neoplastic tissues, but in which these processes are tightly regulated. In the present study, we analyzed the expression of HMGI(Y) in the human placenta using immunohistochemistry. We found expression of HMGI(Y), with nuclear localization, in the villous cytotrophoblast (vCT), which is a highly proliferative cell type. In contrast, the majority of the nuclei of the villous syncytiotrophoblast, a terminally differentiated tissue, was negative. Interestingly, expression of HMGI(Y) was strongest in anchoring villi at the implantation site and in extravillous (intermediate) trophoblast (EVT) invading the maternal decidua. As vCT cells differentiate to become EVT, the HMGI(Y) protein appears to switch from a nuclear to a cytoplasmic localization. Expression of HMGI(Y) in isolated trophoblast populations in primary cell culture was also confirmed using Western-blot analysis. This study shows for the first time expression and localization of HMGI(Y) in the subpopulations of placental tissue.

Unlabelled: Irradiation damage to salivary glands leads to loss of function and fibrosis. Immunohistochemical analysis of extracellular matrix proteins might give a more precise insight into the irradiation damage of glands. Collagen I (C-I) is a major component of the extracellular space. The aim of this study was to analyse the effects of irradiation on the distribution pattern of C-I in the salivary glands of rats., Materials and Methods: Sixty female Wistar rats were fractionated irradiated up to 60 Gy (left side of the neck; 2 Gy/d, 5d/week; total dosage either 20, 40 or 60 Gy). The glands were explanted after 6 or 12 months following supravital anesthesia, the shielded right gland serving as internal control. C-I was detected immunohistochemically., Results: In non-irradiated animals the immunoreaction was mainly homogeneous and slight around the ductal epithelia, in the area of the capsule and septae and the peri- and epineurium of nerves. A statistically significant difference was identified in the irradiated rats vs control animals and comparing in-the-radiation field (left side) vs outside-the-radiation field (right side) situated glands. Multivariate analysis revealed a statistically significant increase in staining of irradiated rats concerning the excretory ducts, the area of the capsule and septae, the nerves and striated ducts and adventitia of vessels [p = 0.0001]. The increase of immunoreaction in irradiated glands started above 20 Gy total dosage and was at its maximum after 60 Gy. However, the expression profile was inhomogenous following 20 Gy exposure and did not differ statistically from glands of control animals. Neither the age of the animals nor the latency period following exposure to the radiation source yielded a statistically significant effect on the immunoreaction., Conclusion: Studies on irradiation damage to the salivary glands require a more detailed description of the proteins accumulating in the extracellular space, thereby forming the so-called "fibrosis". These accumulations of proteins, e.g. C-I, may both support apoptosis and support a hypoxic environment giving rise to transformed cells.

Objective: Basement membranes-(BM) influence polarization, differentiation, migration and proliferation of cell and play an important role in maintaining structural and functional tissue integrity. While BM alterations have been reported in various lesions (e.g. inflammation, tumors) of laryngeal-tracheal tissues, reports on radiogenic BM alterations are rare. External irradiation (IRR) of advanced head and neck tumors often includes "normal tissues" (tissues without cancer) of the larynx. In these normal tissues both single-cell damage (necrosis, apoptosis, functional cell death) and interstitial damage (edema, fibrosis, vascular alterations, cellular infiltrations) resulting in tissue remodeling can occur, depending on various IRR parameters. In this study, we set out to add to our knowledge on the phenotypic characterization of the radiogenic BM expression pattern in laryngo-tracheal tissues., Materials and Methods: In 63 laryngo-tracheal specimens from Wistar rats, we investigated the laminin (LA) and collagen IV (CIV) expression profile and distribution pattern depending on the IRR dose (fractionated IRR, 2 Gy/day, up to a total dose of 20, 40, or 60 Gy), the time since IRR (6 months vs 12 months) and animal age (1 year vs 1.5 years) using immunohistochemical methods, semiquantitative assessment, and multivariate analysis., Results: In specimens irradiated with more than 20 Gy, both BM constituents predominantly showed dose-dependent increases and sometimes fluctuations in staining at slight to moderate levels. The expression differed in frequency and level among the various tissue structures. In some structures there was decreased expression. In the vocalis muscle, laryngeal and esophageal nerve endings, recurrent laryngeal nerve and laryngeal and tracheal muscles, LA was detected at levels significantly stronger than in controls. BM surrounding gland structures, nerve endings of the piriform sinus and esophageal muscles showed a marked tendency towards increased LA expression. However, the BM underlying the mucosal layer of the supra- and subglottic region revealed decreasing LA immunoreaction up to 40 Gy IRR, but a distinct increase in expression at 60 Gy. In the esophageal and tracheal muscles, tracheal perichondrium, recurrent laryngeal nerve and capillaries, CIV was detected at significantly stronger levels than in the controls. The vocal ligament exhibited positive CIV immunoreactions adjacent to interstitial and infiltrate cells and CIV-positive BM condensations, resulting in increased staining of these structures. CIV reactions of laryngeal and hypopharyngeal nerve endings tended towards increased expression. In contrast, BM staining surrounding vocal muscle cells revealed significantly decreased expression. In addition, there was a tendency towards decreased expression for supraglottic, subglottic and hypopharyngeal muscle cells. Age and time since irradiation had no significant effect on staining., Conclusion: The BM constituents laminin and collagen IV showed prominent dose-dependent increases and sometimes fluctuations in expression. This expression pattern persisted up to one year after completion of the irradiation. Thus, these findings must be related to late radiation effects. The altered BM expression may play a role, at least in part, in structural (e.g. laryngeal edema) and functional (voice disorders) changes associated with irradiation of the head and neck area.

Aim: A clinical presentation of Langerhans cell histiocytosis (LCH) in the maxillary sinus of two patients is given. LCH in the maxillary sinus is a rare occurrence. Our aim was to compare the different treatment alternatives available and to suggest a classification as well as a therapeutic regime., Patients and Method: Records and clinical data of two patients treated between 1994 and 2001 were retrospectively evaluated. Both patients suffered from LCH in the maxillary sinus and the maxilla regions. Only surgical treatment was used. After resection, a large defect of the maxillary sinus, which did not allowing coverage, was seen in both cases. After reconstructive operations, closure was finally achieved. Both patients underwent follow-ups, whereby one suffered from a relapse after 15 months., Results: Although one of the patients under investigation showed a recurrence of LCH, we are of the opinion that surgical treatment is very effective in the elimination of this condition. A proposal for a classification of LCH in the oral-maxillo-facial-region is made., Conclusions: The evaluation of our clinical study suggests that LCH is a disease that should be treated surgically. Only in very severe cases should the surgical treatment be complimented by either radiotherapy or chemotherapy. In disseminated cases, especially chemotherapy seems to improve the outcome. Surgery offers the possibility of eliminating systemic side effects.