Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity.

OBJECTIVES: Cholesteatoma is a nonneoplastic destructive lesion of the temporal bone with debated pathogenesis and bone resorptive mechanism. Both molecular and cellular events chiefly master its activity. Continued research is necessary to clarify factors related to its aggressiveness. We aimed to investigate the expression of Ki-67, cytokeratin 13 (CK13) and cytokeratin 17 (CK17) in acquired nonrecurrent human cholesteatoma and correlate them with its bone destructive capacity. METHODS: A prospective quantitative immunohistochemical study was carried out using fresh acquired cholesteatoma tissues (n=19), collected during cholesteatoma surgery. Deep meatal skin tissues from the same patients were used as control (n=8). Cholesteatoma patients were divided into 2 groups and compared (invasive and noninvasive) according to a grading score for bone resorption based upon clinical, radiologic and intraoperative findings. To our knowledge, the role of CK17 in cholesteatoma aggressiveness was first investigated in this paper. RESULTS: Both Ki-67 and CK17 were significantly overexpressed in cholesteatoma than control tissues (P<0.001 for both Ki-67 and CK17). In addition, Ki-67 and CK17 were significantly higher in the invasive group than noninvasive group of cholesteatoma (P=0.029, P=0.033, respectively). Furthermore, Ki-67 and CK17 showed a moderate positive correlation with bone erosion scores (r=0.547, P=0.015 and r=0.588, P=0.008, respectively). In terms of CK13, no significant difference was found between cholesteatoma and skin (P=0.766). CONCLUSION: Both Ki-67 and CK17 were overexpressed in cholesteatoma tissue and positively correlated with bone resorption activity. The concept that Ki-67 can be a predictor for aggressiveness of cholesteatoma was supported. In addition, this is the first study demonstrating CK17 as a favoring marker in the aggressiveness of acquired cholesteatoma.

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives.

Cholesteatoma is a cystic non tumorous lesion of the temporal bone that has the ability to destroy nearby structures by its power to cause bone resorption and as a result, fatal complications prevail. We aimed to conduct a comprehensive review for pathogenesis of acquired cholesteatoma, bone resorption mechanisms, and offer a future vision of this serious disease. We have reviewed different theories for pathogenesis of acquired cholesteatoma including the most relevant and updated ones with special emphasis on the mechanisms of bone resorption through Medline/PubMed research using the keywords 'aetiopathogenesis, bone resorption, acquired cholesteatoma, temporal bone, and cytokines.' In order to strengthen our study, we searched the reference lists of identified reviews. Cholesteatoma is a subject of debate among otolaryngologists since it was prescribed firstly. Over many decades, several theories were postulated for aetiopathogenesis of cholesteatoma with a tendency to follow more than one theory to explain the proper nature of that disease. Until now, the mechanism of bone resorption has yet to be more clarified. In the last century, a leap has occurred in the field of biomolecular cholesteatoma research which improved our knowledge about its pathophysiology and bone destructive mechanism. However, surgery is still the only available treatment. We conclude that discovery of new therapeutic choices for cholesteatoma other than surgery by the use of anti-growth, anti-proliferative, apoptotic agents as well as medications that antagonize osteoclastogenesis should be the main concern in the future clinical and experimental research work. Also, searching for predictors of the aggressiveness of cholesteatoma can affect the timing of intervention and prevent occurrence of complications.

The postoperative histologic changes in the nasal mucosa following treatment with amoxycilline or rifampicin: preliminary findings.

This study examines the postoperative histologic changes in the nasal mucosa following treatment with amoxycilline or rifampicin. Three groups of nasal mucosal biopsies were obtained from 20 patients having undergone nasal surgery (partial middle turbinectomy). The first group was obtained immediately before surgery (control group). The second and third groups were taken postoperatively (after the first and 6 weeks of amoxycilline or rifampicin therapy, 10 patients each). The histologic changes in the nasal mucosa and the density of seromucinous glands were examined using histochemical methods and image analyzer. Amoxycilline treatment was associated with squamous metaplasia and a statistically significant reduction in the percent area of the seromucinous glands compared to the control group (p < 0.05). Rifampicin therapy was associated with minimal reduction in the density of the seromucinous glands and absence of metaplastic changes. In nasal surgeries, rifampicin but not amoxycilline had a beneficial effect on postoperative nasal mucosa status.

The role of genetic susceptibility in head and neck squamous cell carcinoma.

Our research is an additional genetic study to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying loss of heterozygosity (LOH) and microsatellite instability (MSI) in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. Patients with HNSCC from various parts of the world may have unique genotypes and this is the first genetic study of HNSCC in Sohag 500 KM to the south of Cairo. We performed a prospective study of 41 patients with precancerous and 79 patients with cancerous laryngeal, esophageal, nasopharyngeal, nasal and oral lesions, and 50 controls (The control patients were cases admitted for ear surgery or simple nasal surgery, from whom we took biopsy from mucosal lining of nasopharynx). The present study included 170 individuals who were admitted to the Ear, Nose and Throat department, Sohag University Hospital, Sohag, in Egypt in the period between April 2001 and March 2003. Samples which were taken by punch biopsy were frozen and stored at -80 degrees C and were subjected to histopathological examination. We investigated LOH and MSI by using six microsatellite markers located at chromosomes 3, 5, 9, and 17. The markers used were D3S1286, D9S171, D9S753, D17S654, D17S695, and CFS1-R. LOH was in all premalignant and malignant lesions at 5q33.3-q34 and 13% of Controls. LOH at 17p21 was absent in all premalignant lesions and was found in 53% of malignant lesions and 12.4% of Controls. In premalignant lesions, LOH was at 3pter-3p24.2 (73% of cases), at 9p21 (46%), at 9q21.1-22.3 (37%), and at 17p13 (37%). These percents increased in malignant lesions to 87, 80, 67, and 63%, respectively. They were 14, 19.4, 17, and 19% in controls. Examination of LOH could improve diagnosis, adds additional confidence, in HNSCC by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and LOH at 3p/9p seems to be of particular value for early detection and definition of progression risk. If there are high percent of LOH at these chromosomes, active intervention should be done (chemoprevention and regular follow up head and neck examination for very early detection and management).