Immunoprofile of Kuttner tumor (chronic sclerosing sialadenitis)

In the present study, the immunoprofile of chronic sclerosing sialadenitis, also known as Kuttner tumor, was analyzed. Two,cases that occurred in the submandibular gland of male patients were submitted to immunohistochemical reactions to different antibodies. Histological examinations showed a submandibular gland exhibiting various degrees of atrophy with destruction of acini, infiltration by inflammatory cells, and periductal fibrosis. Reactions to cytokeratins (CKs) showed acini and duct remnants positive to CKs 7, 8, 19, and 13. CK14 stained myoepithelial cells around preserved acini and intercalated duct, and also basal cell of excretory ducts, but was negative in proliferating and branching ducts. Smooth muscle actin (SMA) was expressed by myofibroblasts in periductal fibrosis, and an intense expression of extracellular components was also seen. Lymphocyte markers showed, besides mature follicles, a higher presence of CD45RO positive cells. Thus, the immunoprofile of Kuttner is much more in keeping with an inflammatory-induced degenerative disease than with a preneoplastic lesion.

Oral lesions and immune reconstitution syndrome in HIV+/AIDS patients receiving highly active antiretroviral therapy. Epidemiological evidence

Objective: To determine whether opportunistic oral infections associated to HIV infection (OOI-HIV) are found in HIV+/AIDS patients with immune reconstitution related to highly active antiretroviral therapy (HAART). Methods. From among 1100 HIV+/AIDS patients (Service of Internal Medicine, Carlos Haya Hospital, Malaga, Spain) subjected to review of the oral cavity between January 1996 and May 2007, we identified those examined in 1996 and which were again examined between 1997 and 2007, and were moreover receiving HAART. The following data were collected: age, gender, form of contagion, antiretroviral therapy at the time of review, number of CD4+ lymphocytes/ml, and viral load (from 1997 onwards). We identified those subjects with an increase in CD4+ lymphocytes/ ml associated to HAART, and classified them as subjects with quantitative evidence of immune reconstitution (QEIR). Among these individuals with QEIR we moreover identified those with undetectable viral loads (QEIR+VL), and differentiated those patients with an increase in CD4+ lymphocytes > 500/ml (QEIRm+VL). In each group we determined the prevalence of OOI-HIV, following the diagnostic recommendations of the EC-Clearinghouse (CDC-Atlanta, USA - WHO). In addition, we analyzed the prevalence of OOI-HIV in the different groups in relation to the duration of HAART. Results. A total of 86 subjects were included (44 females and 42 males; 19 heterosexuals, 34 male homosexuals, and 33 intravenous drug abusers). Forty-two patients showed QEIR: 21 belonged to the QEIR+VL group, and 17 conformed the QEIRm+VL group. The prevalence of OOI-HIV per group was as follows: QEIR = 54.8%; QEIR+VL = 33%; QEIRm+VL = 35%. The most prevalent lesion in all groups was erythematous candidiasis. OOI-HIV increased with the duration of HAART (p=0.008), and were seen to be dependent upon late appearance of the mycotic lesions ( after 24 months under HAART). Conclusions: It is suggested that opportunistic oral infections associated to HIV infection form part of the clinical picture of immune reconstitution inflammatory syndrome, though such infections are of late onset.

Angiomyolipomatous hamartoma of the upper lip: A rare case in an 8-month-old child and differential diagnosis

Hamartoma is a proliferation of normal tissues that are considered endogenous to the site of occurrence. In the head and neck region, hamartomas composed of other tissues different from blood and lymphatic vessels (hemangiomas and lymphangiomas) are very uncommon. We report an unusual case of upper lip angiomyolipomatous hamartoma in an 8-month-old patient. The patient underwent surgical treatment and the 1-year follow-up revealed no signs of recurrence. Angiomyolipomatous hamartoma is a very rare condition in the paediatric population group, especially in the head and neck region. It should be considered in the differential diagnosis of congenital lesions in childhood. (C) 2010 European Association for Cranio-Maxillo-Facial Surgery.

Kaposi sarcoma and paracoccidioidomycosis in the same fragment of oral mucosa biopsy: a rare association in human immunodeficiency virus-positive patient. A case report

The immunossuppression caused by HIV infection makes the affected individuals more susceptible to some diseases including infections, neoplasms, or even the association between them. Kaposi sarcoma (KS) is the most common AIDS-related neoplasm, featured as an angioproliferative disorder. Its cause seems to be related to the human herpesvirus type 8 and it is usually associated with lower CD4+ T cell count. Oral involvement is frequent, presenting red to blue-purplish plaques, maculaes, and nodules. On the other hand, paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in Latin America, caused by Paracoccidioides brasiliensis. This mycosis is not commonly related to human immunodeficiency virus (HIV) infection, although PCM can be present in immunosuppression cases. Oral lesions, as granulomatous ulcers, are often identified in seropositive patients with PCM. A rare case, in which a male HIV-positive patient presented simultaneously Kaposi sarcoma and PCM in the same fragment of oral mucosa biopsy, is described. To the best of our knowledge, this concomitant association had not been previously described. (C) 2011 Elsevier Inc. All rights reserved.

Altered beta-catenin expression related to cancer progression on actinic cheilitis and squamous cell carcinoma of the lip

beta-Catenin is a bifunctional protein related to cell adhesion and gene transcription when activated by Wnt pathway. Altered expression of beta-catenin was related to loss of differentiation, more aggressive phenotype, increase of tumor invasion, and poor prognosis in a number of different cancers. Actinic cheilitis is caused by excessive exposure to ultraviolet radiation and has a high potential to suffer malignant transformation into squamous cell carcinoma (SCC) of the lip, the most frequent oral malignancy. Studies of oral cancer have shown the correlation of beta-catenin expression and oral SCC prognosis, and loss of membrane expression may be considered as a potential marker for early tumor recurrence. Thirty-five cases of actinic cheilitis and 12 cases of SCC of the lip were select and submitted to immunohistochemical staining using beta-catenin antibody. beta-Catenin was positive on the membrane for all cases. Eighty-five percent of actinic cheilitis cases showed cytoplasmatic staining, and 22% nuclear staining. Eighty-three percent of SCC was positive for beta-catenin, and none of them had nuclear staining. Cytoplasmatic and nuclear staining of beta-catenin on studied cases point to pathway alterations. Results demonstrated that beta-catenin expression is altered on epithelial dysplasia, and it is related to degree of alterations. (C) 2011 Elsevier Inc. All rights reserved.

Detection of TGIF1 homeobox gene in oral squamous cell carcinoma according to histologic grading

Objective. TGIF1 homeobox gene involvement in oral cancer has not yet been investigated. This study analyzed the expression of TGIF1 transcripts and protein in oral squamous cell carcinoma (OSCC). Study design. Snap-frozen samples from 16 patients were taken from both OSCC and nontumoral adjacent epithelium (NT) for in situ hybridization (ISH). Forty-six paraffin-embedded samples of OSCC were submitted to immunohistochemistry (IHC). A descriptive analysis of the transcript signal detection was accomplished, and TGIF1 immunoexpression was carried out considering protein levels, localization, and cellular differentiation. Results. ISH reactions showed TGIF1 transcripts with a signal that was frequently intense in NT, and generally weak in OSCC, and that had stronger transcript signal in well-differentiated areas of OSCC when compared with poorly differentiated ones. IHC reactions had poorly differentiated cases associated with TGIF1 protein expression in both the nucleus and cytoplasm (P = .05, Fisher test). Conclusions. TGIF1 gain or loss of function might possibly play a role in oral cancer cell differentiation. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011; 111: 218-224)

Expression of Homeobox Genes in Oral Squamous Cell Carcinoma Cell Lines Treated With All-Trans Retinoic Acid

Oral squamous cell carcinoma (OSCC) may arise from potentially malignant oral lesions. All-trans retinoic acid (atRA), which plays a role in cell growth and differentiation, has been studied as a possible chemotherapeutic agent in the prevention of this progression. While the mechanism by which atRA suppresses cell growth has not been completely elucidated, it is known that homeobox genes are atRA targets. To determine if these genes are involved in the atRA-mediated OSCC growth inhibition, PCR array was performed to evaluate the expression of 84 homeobox genes in atRA-sensitive SCC-25 cells compared to atRA-resistant SCC-9 cells following 7 days with atRA treatment. Results showed that the expression of 8 homeobox genes was downregulated and expression of 4 was upregulated in SCC-25 cells but not in SCC-9 cells. Gene expression levels were confirmed for seven of these genes by RT-qPCR. Expression of three genes that showed threefold downregulation was evaluated in SCC-25 cells treated with atRA for 3, 5, and 7 days. Three different patterns of atRA-dependent gene expression were observed. ALX1 showed downregulation only on day 7. DLX3 showed reduced expression on day 3 and further reduced on clay 7. TLX1 showed downregulation only on days 5 and 7. Clearly the expression of homeobox genes is modulated by atRA in OSCC cell lines. However, the time course of this modulation suggests that these genes are not direct targets of atRA mediating OSCC growth suppression. Instead they appear to act as downstream effectors of atRA signaling. J. Cell. Biochem. 111: 1437-1444, 2010. (C) 2010 Wiley-Liss, Inc.

A role for COX2-derived PGE2 and PGE2-receptor subtypes in head and neck squamous carcinoma cell proliferation

The overexpression of cyclooxygenase (COX)-2 is a frequent event in squamous cell carcinomas of the head and neck (HNSCC), and non-steroidal anti-inflammatory drugs, which are potent inhibitors of COX-1 and COX-2, exert chemopreventive effects on HNSCC cancer development. COX-2 promotes the release of the pro-inflammatory mediator prostaglandin E2 (PGE2), which acts on its cell surface G protein-coupled receptors EP1, EP2, EP3, and EP4. Here, we investigated the role of PGE2 and its receptors in cellular proliferation in HNSCC. The expression of COX-2 and EP1-4 was examined in immortalized oral epithelial cells and in a representative panel of HNSCC cell lines, and based on these data EP1-EP3 and COX-2 expression were evaluated by immunohistochemistry in a large clinical sample collection using HNSCC tissue microarrays. The ability of selective COX-2 inhibition to block PGE2 secretion was measured by ELISA specific assays. The effects of PGE2 on cell proliferation were evaluated using PGE2, its stable analog, and EP2 and EP3-specific synthetic agonists. The results presented here show that HNSCC tumoral lesions and their derived cell lines constitutively express COX-2 and the EP1, EP2 and EP3 receptors for PGE2. HNSCC cells secrete PGE2, which can be suppressed by low concentrations of COX-2 selective inhibitors, without inhibiting cell proliferation. Exogenously added stable PGE2 and EP3-specific agonists induce DNA synthesis in all HNSCC cell lines tested. Overall, our study supports the emerging notion that PGE2 produced in the tumor microenvironment by the overexpression of COX-2 in tumoral and inflammatory cells may promote the growth of HNSCC cells in an autocrine and paracrine fashion by acting on PGE2 receptors that are widely expressed in most HNSCC cancer cells. In particular, our findings suggest that EP3 receptor may play a more prominent role in HNSCC cell growth promotion, thus providing a rationale for the future evaluation of this PGE2 receptor as a target for HNSCC prevention strategies. Published by Elsevier Ltd.

Solitary Neurofibroma of the Temporal Bone

Neurofibroma is a benign peripheral nerve sheath tumor that can be occasionally found in the head and neck region as multiple lesions associated with neurofibromatosis type 1 (NF-1) or as a solitary tumor. The real frequency of isolated neurofibromas not associated with NF is uncertain, and lesions in the temporal region are extremely rare. The aim of the current article was to report an unusual case of solitary neurofibroma localized in the temporal and infratemporal regions with 10 years of evolution in a female patient without any other manifestation or familiar history of NF-1. The patient underwent surgical treatment for complete excision of the lesion, and the 2-year follow-up revealed no signs of recurrence.

Oral squamous cell carcinoma: status of tight junction claudins in the different histopathological patterns and relationship with clinical parameters. A tissue-microarray-based study of 136 cases

Aims Claudins are integral transmembrane proteins of the tight junctions, critical for maintaining cell adhesion and polarity. Alterations in the expression of individual claudins have been detected in carcinomas and appear to correlate with tumour progression. Methods In this study, a panel of anti-claudin antibodies (anti-claudins 1, 2, 3, 4, 5 and 7) was employed to map claudin expression in 136 cases of oral squamous cell carcinoma (OSCC) organised in a tissue microarray. Results Claudins were expressed in a reticular pattern up to the prickle layer in normal mucosal epithelium. In OSCC, claudins were strongly present in well-differentiated tumours, they presented mild and low expression in moderately differentiated OSCC, and were negative in poorly differentiated OSCC; the absences of claudin 1 (p = 0.002) and claudin 4 (p<0.001) were associated with moderately/poorly differentiated tumours. Strong expression of claudin 4 was associated with decreased perineural infiltration (p = 0.024). Claudins 5 and 7 were mostly negative or weakly expressed in all cases studied. Expression of claudin 7 was associated with the early clinical stages of the disease, whereas loss of claudin 7 tended to be more frequent in advanced stages of OSCC (p = 0.054). Absence of claudin 7 was also associated with absent vascular infiltration (p = 0.045) and with presence of recurrence (p = 0.052). Conclusions Claudin expression patterns showed a strong correlation with histological type of OSCC; claudin expression was decreased in areas of invasion, and negative in poorly differentiated tumours. This pattern may be related to evolution and prognosis of these tumours, especially in the case of claudin 7, which seems to be associated with a poor prognosis in OSCC.

Oral manifestations of human T-cell lymphotropic virus infection in adult patients from Brazil

Objective: Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus discovered and its pathogenesis is related to T cells infection. This study aimed to verify the presence of oral manifestations in a Brazilian population of patients who was seropositive for HTLV, and identify risk factors for oral manifestations. Subjects and methods: An assessment was made of 139 patients at the Emilio Ribas Institute of Infectious Diseases. Results: A total of 112 (80.5%) patients were HTLV-1, 26 (18.7%) were HTLV-2+. About 35.2% of patients had myelopathy/tropical spastic paraparesis (HAM/TSP), with 48 of them being HTLV-1+ and one patient was seropositive for HTLV-1 and -2. The most common oral manifestations were: xerostomia (26.8%), candidiasis (20.8%), fissured tongue (17.9%), and loss of tongue papillae (10.0%). A multivariate logistic regression analysis showed that HAM/TSP is an independent risk factor for xerostomia (P = 0.02). The patients who were HAM/TSP+ were three times more likely to develop xerostomia when compared with patients without HAM/TSP (odds ratio = 2.69, 95% confidence interval = 1.17-6.17). Conclusion: Despite the fact that the findings of this study suggest a relationship between xerostomia and HAM/TSP, more studies should be developed to show what the association would be between xerostomia presented by HTLV patients and pathogenesis of the virus.

Oral status and Candida colonization in patients with Sjogren`s Syndrome

Objective: To determine the oral status, salivary flow rate, Candida carriage in saliva, and prevalence of Candida albicans colonization in several areas of the mouth in patients with primary and secondary Sjogren`s syndrome as opposed to those of healthy subjects. Study design: Thirty-seven patients with Sjogren`s syndrome (SS), [14 patients with primary SS (SS-1) and 23 patients with secondary SS (SS-2)], along with 37 healthy controls were examined in regard to number of teeth, pro-bing pocket depth (PPD), approximal plaque index (API), bleeding on probing (BOP), presence of prosthetic appliances and smoking habits. Salivary flow rate (SFR), Candida carriage in saliva, presence of Candida albicans colonization on buccal, angular, palatal and sulcular areas, on dentures and on the tongue`s dorsal surface were determined. Statistical analyses were performed using the 2-tailed Fisher exact and Kruskal-Wallis test. Results: No statistically significant difference was found between SS-1 and SS-2 groups based on the parameters analysed. Statistically significant differences were observed between patients with SS and healthy subjects in terms of SFR, oral signs and symptoms, API, BOP, C. albicans colonization on tongue and buccal area, and Candida carriage in saliva. In the gingival crevicular fluid positive C. albicans colonization was found in only one subject of SS subgroup. Conclusions: SS patients carry a higher risk of having periodontitis and are more predisposed to develop candidiasis. C. albicans is scarcely detected in gingival crevicular fluid despite high scores on C. albicans colonization in different areas of the oral cavity in SS patients.

Differential expression of galectin-3, beta-catenin, and cyclin D1 in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma of salivary glands

Background: Galectin-3 has been implicated in tumor progression of some malignancies as thyroid, prostate, and salivary gland tumors. Recently, it has been suggested that this protein may be an important mediator of the beta-catenin/Wnt pathway. Moreover, nuclear galectin-3 expression has been implicated in cell proliferation, promoting cyclin D1 activation. Thus, the present study aimed to correlate galectin-3 expression with beta-catenin and cyclin D1 expressions in adenoid cystic carcinoma (ACC) and in polymorphous low-grade adenocarcinoma (PLGA). Methods: Fifteen formalin-fixed paraffin-embedded cases of each tumor were retrieved from the files of the Surgical Oral Pathology Service at the University of Sao Paulo and the proteins were analyzed by immunohistochemistry. Results: Adenoid cystic carcinoma showed galectin-3 immunostaining mainly in the nuclei, while PLGA revealed a positive mostly cytoplasmic reaction to galectin-3 in the largest part of tumor cells. Both tumors showed intense cytoplasmic/nuclear staining for beta-catenin in majority of cases. Cyclin D1 immunoreactivity was not detected in 14/15 PLGA and showed specific nuclear staining in 10/15 cases of ACC in more than 5% of the neoplastic cells. Cyclin D1 expression was correlated with cytoplasmic and nuclear galectin-3 expression in ACC (P < 0.05). Conclusions: These results suggest that in ACC galectin-3 may play a role in cellular proliferation through cyclin D1 activation. In addition, nuclear expression of galectin-3 in ACC may be related to a more aggressive behavior of this lesion. Although beta-catenin seems to play a role in carcinogenesis in both lesions, it seems that it does not bind to galectin-3 for cyclin D1 stimulation.

WNT-5A, but not matrix metalloproteinase 3 or beta-catenin protein, expression is related to early stages of lip carcinogenesis

Background: Oncogenic Wnt/beta-catenin signaling occurs in numerous types of cancers, but little is known about the role of the Wnt protein family member, WNT-5A, in lip carcinogenesis. The aim of this study was to investigate WNT-5A, beta-catenin, and matrix metalloproteinase (MMP)-3 protein expression in actinic cheilitis (AC), and lip squamous cell carcinoma (LSCC). Methods: Twenty-one cases of AC, and fifty-one cases of LSCC were analyzed, with normal lip mucosa used as a control. Qualitative and semi-quantitative analyses of WNT-5A, beta-catenin, and MMP-3 immunostaining pattern and cellular distribution were performed. Results: WNT-5A was observed in more than 50% of the cells, scattered in all layers of AC, in contrast to the absence of immunostaining in normal lip mucosa. AC presented a higher level of WNT-5A expression than LSCC (P = 0.0289, Fisher test), while MMP-3 immunoexpression was statistically more significant in LSCC than in AC (P = 0.0285, Fisher test). Immunolabeling of beta-catenin protein was differentially distributed between samples; the majority of AC cases (61.90%) demonstrated a membranous-cytoplasmic pattern, while a considerable number of LSCC cases (29.41%) revealed a cytoplasmic pattern, instead of the usual membranous pattern. Conclusions: The present results suggest that WNT-5A may be an important marker during initial events of AC malignant transformation, in which non-canonical and canonical Wnt/beta-catenin signaling pathways could be involved. Additionally, WNT-5A might recruit other events in LSCC, such as MMP-3 protein synthesis, as its presence is increased in established malignant processes without beta-catenin dependency.

Glial fibrillary acidic protein in tumor types with cartilaginous differentiation

Glial fibrillary acidic protein (GFAP) is a member of the intermediary filament protein family. It is an important component of astrocytes and a known diagnostic marker of glial differentiation. GFAP is expressed in other neural tumors and pleomorphic adenoma and, less frequently, in cartilage tumors, chordomas, and soft tissue myoepitheliomas. The aim of this study was to evaluate the role of GFAP and its reliability in nonglial tumors as an immunohistochemical marker. We evaluated GFAP gene and protein expression using Q-PCR and immunohistochemistry, respectively, in 81 and 387 cases of soft tissue, bone tumors, and salivary pleomorphic adenomas. Immunohistochemistry staining for GFAP was observed in all osteosarcomas (8 cases), all pleomorphic adenomas (7 cases), in 5 of 6 soft tissue myoepitheliomas, and in 21 of 76 chondrosarcomas. By Q-PCR, GFAP was highly expressed in pleomorphic adenomas and, to a lesser extent, chondrosarcomas, soft tissue myoepitheliomas, and chondroblastic osteosarcomas. The results that we obtained by immunohistochemistry and Q-PCR were well correlated. GFAP is a potential marker for tumors with cartilaginous differentiation, supported by evidence that GFAP is expressed in certain cases of myoepithelial tumors by immunohistochemistry, including soft tissue myoepitheliomas, which are related to cartilaginous differentiation. These findings contribute significantly to the diagnosis of soft tissue myoepitheliomas with cartilaginous differentiation and chondroblastic osteosarcoma in mesenchymal tumors. Modern Pathology ( 2009) 22, 1321-1327; doi: 10.1038/modpathol.2009.99; published online 7 August 2009