Sibel Elif Gültekin

P16(INK4A) immunostaining is a strong indicator for high-risk-HPV-associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low-risk-HPV-infection in head and neck papillomas and laryngeal dysplasias

Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16INK4A is often used as a surrogate marker for HPV‐infection, although there is still controversy with respect its reliability. Our aim was to determine if p16INK4A overexpression can accurately predict both high‐risk and low‐risk‐HPV‐presence in (pre)malignant and benign head and neck lesions. P16INK4A immunohistochemistry was performed on paraffin‐embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC), 14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal papillomas. PCR, enzyme‐immunoassay and FISH analysis were used to assess HPV‐presence and type. Of the 162 OPSCC and 14 tonsillar dysplasias, 51 (31%) and 10 (71%) were HPV16‐positive, respectively. All tonsillar papillomas were HPV‐negative and four laryngeal dysplasias and 26 laryngeal papillomas were positive for HPV6 or −11. P16INK4A immunohistochemistry revealed a strong nuclear and cytoplasmic staining in 50 out of 51 HPV16‐positive and 5 out of 111 HPV‐negative OPSCC (p < 0.0001) and in all HPV16‐positive tonsillar dysplasias, whereas highly variable staining patterns were detected in the papillomas and laryngeal dysplasias, irrespective of the HPV‐status. In addition, the latter lesions generally showed a higher nuclear than cytoplasmic p16INK4A immunostaining intensity. In conclusion, our data show that strong nuclear and cytoplasmic p16INK4A overexpression is a reliable surrogate indicator for HPV16 in OPSCC and (adjacent) dysplasias. For HPV6 or −11‐positive and HPV‐negative benign and premalignant lesions of the tonsil and larynx, however, p16INK4A immunostaining is highly variable and cannot be recommended to predict HPV‐presence.

Effects of Low-Dose Doxycycline and Bisphosphonate Clodronate on Alveolar Bone Loss and Gingival Levels of Matrix Metalloproteinase-9 and Interleukin-1β in Rats With Diabetes: A Histomorphometric and Immunohistochemical Study

BACKGROUND Bisphosphonates (BPs) and low-dose doxycycline (LDD) have been shown to inhibit bone resorption and to improve the levels of proinflammatory mediators and destructive enzymes in gingival tissues, respectively. The purpose of this study is to evaluate the effect of mono and combined BP clodronate and LDD therapies in reducing gingival levels of matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), and alveolar bone loss in rats with diabetes. METHODS Fifty adult Wistar rats were divided into five study groups as follows: 1) group 1 = diabetes control; 2) group 2 = diabetes + periodontitis; 3) group 3 = diabetes + periodontitis + LDD; 4) group 4 = diabetes + periodontitis + clodronate; and 5) group 5 = diabetes + periodontitis + LDD + clodronate. LDD and clodronate were given as a single agent or as combination therapy during the 7 days of the post-experimental periodontitis period. On day 7, the rats were sacrificed, the mobility of the tooth was recorded, and block biopsies were removed. The gingival tissues were analyzed histologically and immunohistochemically for expression of MMP-9 and IL-1β. Alveolar bone loss was evaluated morphometrically under a light microscope. Data analysis was performed statistically by Kruskal-Wallis and post hoc Tukey and Spearman correlation tests. RESULTS Alveolar bone loss was significantly greater in groups 2 through 5 than group 1 (P <0.05) but was not significantly different among groups 2 through 5 (P >0.05). Animals with periodontitis (group 2) expressed significantly higher levels of MMP-9 and IL-1β compared with those without periodontitis (group 1) (P <0.05). MMP-9 expression was significantly lower in group 3 than groups 1, 2, and 5 (P <0.05). IL-1β expression was significantly lower in the groups 1, 3, 4, and 5 than 2 (P <0.01) but was not significantly different among groups 1, 3, 4, and 5. Positive correlations were found between alveolar bone loss and density of inflammation (ρ = 0.319, P = 0.021) and between MMP-9 and IL-1β (ρ = 0.418, P = 0.002), respectively. CONCLUSION Our findings suggest that ligature-induced periodontitis in animals with diabetes results in significantly higher levels of MMP-9 and IL-1β expression in gingiva. The use of mono and combined clodronate and LDD administrations may significantly reduce levels of MMP-9 and IL-1β expression. However, drug administration did not affect alveolar bone levels during the study period.

Parosteal osteochondrolıpoma of the mandıble

Osteochondrolipoma is a rare benign soft tissue neoplasm. It is occasionally considered to be a variant of adipose tissue neoplasm ‘lipoma’ showing multiple differentiation pathways of pluripotent stem cells. As with the lipomas they can be seen at any location and show cartilagenous and osteoid differentiation when located parosteally. We present a case of osteochondrolipoma located at the symphysis of the mandible. To our knowledge, this is the first reported case of an oral osteochondrolipoma associated with parosteal localization.

Effect of the Topical Use of the Antioxidant Taurine on the Two Basement Membrane Proteins of Regenerating Oral Gingival Epithelium

BACKGROUND The essential amino acid taurine has important physiologic and pathologic roles, and has been shown to have osmoregulatory, antioxidative, antiapoptotic, anti-inflammatory, and antilipid activities. However, the response of oral gingival epithelium to taurine during wound healing remains unclear. The goal of this study is to evaluate the expression of laminin 5 and Type IV collagen histologically in regenerating gingival epithelium after direct application of taurine on incised human gingival samples. METHODS The study was conducted on 16 gingival samples obtained from gingivectomy specimens of eight adult patients with generalized gingival overgrowth. The samples were divided into two groups: gingiva with 1% taurine-hydrated collagen membrane (n = 8) and saline-hydrated collagen membrane (n = 8) applied specimens. The length of the newly formed epithelium on the wound surface and inflammation was assessed on hematoxylin and eosin-stained sections. Basement membrane formation was evaluated by detection of laminin 5 and Type IV collagen expressions on immunohistochemically stained samples. RESULTS Complete new epithelial formation was observed in 1% taurine-treated gingivectomy specimens, whereas incomplete regeneration of the epithelium was observed in control gingivectomy specimens (P <0.05). The length of the newly formed epithelium showed a negative correlation with inflammation in the taurine group (P = -0.712; P <0.05). Immunoreactivity for both laminin 5 and Type IV collagen did not show any significant difference between groups. CONCLUSION The local application of taurine-hydrated collagen membrane on human gingival wounds demonstrated the histologic evidence of rapid reepithelization with taurine.

The landscape of genetic alterations in ameloblastomas relates to clinical features

Ameloblastoma is a mostly benign, but locally invasive odontogenic tumor eliciting frequent relapses and significant morbidity. Recently, mutually exclusive mutations in BRAF and SMO were identified causing constitutive activation of MAPK and hedgehog signaling pathways. To explore further such clinically relevant genotype-phenotype correlations, we here comprehensively analyzed a large series of ameloblastomas (98 paraffin block of 76 patients) with respect to genomic alterations, clinical presentation, and histological features collected from the archives of three different pathology centers in France, Germany, and Turkey. In good agreement with previously published data, we observed BRAF mutations almost exclusively in mandibular tumors, SMO mutations predominantly in maxillary tumors, and single mutations in EGFR, KRAS, and NRAS. KRAS, NRAS, PIK3CA, PTEN, CDKN2A, FGFR, and CTNNB1 mutations co-occurred in the background of either BRAF or SMO mutations. Strikingly, multiple mutations were exclusively observed in European patients, in solid ameloblastomas and were associated with a very high risk for recurrence. In contrast, tumors with a single BRAF mutation revealed a lower risk for relapse. We here establish a comprehensive landscape of mutations in the MAPK and hedgehog signaling pathways relating to clinical features of ameloblastoma. Our data suggest that ameloblastomas harboring single BRAF mutations are excellent candidates for neo-adjuvant therapies with combined BRAF/MEK inhibitors and that the risk of recurrence maybe stratified based on the mutational spectrum.

Lactobacillus rhamnosus could inhibit Porphyromonas gingivalis derived CXCL8 attenuation

ABSTRACT An increasing body of evidence suggests that the use of probiotic bacteria is a promising intervention approach for the treatment of inflammatory diseases with a polymicrobial etiology. P. gingivalis has been noted to have a different way of interacting with the innate immune response of the host compared to other pathogenic bacteria, which is a recognized feature that inhibits CXCL8 expression. Objective The aim of the study was to determine if P. gingivalis infection modulates the inflammatory response of gingival stromal stem cells (G-MSSCs), including the release of CXCL8, and the expression of TLRs and if immunomodulatory L. rhamnosus ATCC9595 could prevent CXCL8 inhibition in experimental inflammation. Material and Methods G-MSSCs were pretreated with L. rhamnosus ATCC9595 and then stimulated with P. gingivalis ATCC33277. CXCL8 and IL-10 levels were investigated with ELISA and the TLR-4 and 2 were determined through flow cytometer analysis. Results CXCL8 was suppressed by P. gingivalis and L. rhamnosus ATCC9595, whereas incubation with both strains did not abolish CXCL8. L. rhamnosus ATCC9595 scaled down the expression of TLR4 and induced TLR2 expression when exposed to P. gingivalis stimulation (p<0.01). Conclusions These findings provide evidence that L. rhamnosus ATCC9595 can modulate the inflammatory signals and could introduce P. gingivalis to immune systems by inducing CXCL8 secretion.

Histologic and histomorphometric assessment of eggshell-derived bone graft substitutes on bone healing in rats

Objective: The objective of this study was to histologically and histomorphometrically evaluate the efficacy of the new formulations of eggshell-derived calcium carbonate in rats. Study Design: The study was conducted on 30 adult male rats. Four standardized and circular intrabony defects were created in the both maxilla and mandibula of each animal. Three different graft materials were prepared as follows: 1) Material A: Eggshell-derived calcium carbonate combined with carrageenan gel, 2) Material B: Eggshell-derived calcium carbonate combined with xanthan gum gel, and 3) Material C: Eggshell-derived calcium carbonate powder. The right mandibular defect sites were grafted with Material A in all animals, and defects on the left were grafted with Material B. Defects on the right side of maxilla were received Material C in all animals, and all left maxillary defects were remained untreated as controls. The animals were sacrificed either postoperatively on the 15th day, postoperatively on the 30th day or postoperatively on the 45th day. Histomorphometric measurements were made of the areas of newly formed bone, necrotic bone, fibrous tissue and residual graft material. Results: Material A exhibited the highest level of osteoid formation followed by Material B and Material C on the 45th day. In terms of osteoid formation, statistically significant differences were observed between graft materials and controls at 45th day compared to 15th and 30th day (p<0.05). Conclusions: Eggshell-derived graft substitutes in both gel and powder forms are biocompatible materials which may have the potential to enhance the new bone formation. Key words:Bone graft material, bone defects, eggshell, histopathological evaluation, rat.

Molecular Profiling of Odontogenic Tumors - Pilot Study

Summary Background/Aim: In the pathogenesis of odontogenic tumors which arise from the rests of the dental apparatus in the jaw, several molecular pathways have been shown to play critical roles such as genetic alterations in the hedgehog, BRAF/Ras/MAPK, epidermal growth factor receptor. Next generation genomic sequencing has identified gene mutations in many different tumors. Materials and Methods: Here we report four types of odontogenic tumor including six cases in which five had mutation according to next generation sequencing analysis from archival paraffin blocks that diagnosed previously as ameloblastoma (solid), amloblastoma (unicystic-mural), ameloblastic fibroma, squamous odontogenic tumor, and adenomatoid odontogenic tumor. Results: All ameloblastomatic tumors were shown BRAF mutation and adenomatoid odontogenic tumors were KRAS mutation. Conclusion: This evidence may highlight the poorly understood pathogenesis of odontogenic tumors. Further comparisons need to be made with other benign and malignant odontogenic tumors so that unique odontogenic features may be found.

Unusual Presentation of an Adenocarcinoma of the Lung Metastasizing to the Mandible, Including Molecular Analysis and a Review of the Literature.

Lung cancer is the most frequent cause of cancer-related death worldwide. Metastases of non-small cell lung carcinoma to the oral and maxillofacial region are rare. Thus, the diagnosis of a metastatic lesion in the oral cavity is challenging to the clinician and to the pathologist. This report presents a case of a 72-year-old man with metastatic lung adenocarcinoma located in the posterior mandibular region. Next-generation sequencing analysis showed no important mutations in the relevant genes except in the TP53 tumor suppressor gene.