The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas.

PURPOSE: To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs). METHODS: In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR. RESULTS: Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2-G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort. CONCLUSIONS: Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.

[Planning and design of European prospective randomized trial on the value of drain in parotidectomy]. / Vorstellung einer europaweiten prospektiven Studie zur Wertigkeit einer Drainage bei Parotidektomie.

INTRODUCTION: There are no valid clinical studies on the value of wound drains in parotid surgery. The aim of the current trial is to analyze the influence of the closed wound drain (redon) on the incidence of postoperative complications such as bleeding, wound healing problems, infection, as well as salivary cyst and fistula after superficial or partial parotidectomy. METHODS: A European-wide multicenter prospective randomized study was planned. The study protocol was prepared by the leading study center (ENT University Hospital Cologne) in cooperation with the ENT University Hospitals Jena and Göttingen. The calculation of the number of cases was carried out with G*Power. The study includes test persons with an indication for parotidectomy for a benign tumor without known coagulation disorder or ongoing anticoagulation. Preoperative randomization and data management is software-supported (REDCap 9.1.24, Vanderbilt University). RESULTS: The study has been approved by the leading ethics committee in 10/2019 and is open since 04/2019. Currently, nine (9) ENT hospitals are participating in the study, 6 of them in Germany and 3 in Austria. Enrollment of patients is ongoing in 7 centers. With a calculated follow-up-to-treat population of 800 test persons, the planned duration of the study is 4 years. CONCLUSIONS: The Redon-study is the first prospective randomized study worldwide to investigate the effect of a drain in parotidectomy. In order to achieve the recruitment goal within the planned time frame, the participation of further specialized study centers is needed. We also encourage all ENT physicians to make their patients aware of the Redon study, inform them about the possibility of participating in the study and refer them to one of the participating centers.

Cancer stage and pack-years, but not p16 or HPV, are relevant for survival in hypopharyngeal and laryngeal squamous cell carcinomas.

PURPOSE: Recently, p16 has been included in the TNM guideline for oropharyngeal carcinomas. The role of HPV and p16 in hypopharyngeal and laryngeal carcinomas has not yet been established sufficiently. METHODS: Hundred and thirty-four patients with hypopharyngeal and laryngeal carcinomas were included in this retrospective analysis. Only patients with known HPV status were eligible for the investigation. Survival probabilities were estimated for different risk factors. RESULTS: Eighty-five patients presented with laryngeal carcinoma and 49 patients with hypopharyngeal carcinoma. 8% were HPV positive (10.6% laryngeal, 4.1% hypopharyngeal carcinoma). Median follow-up time was 58 months. We observed a significantly better overall survival for patients with an early tumor stage compared to advanced carcinoma. One of the hypopharyngeal HPV positive carcinomas was also p16 positive and one was p16 negative. Of the nine HPV positive laryngeal carcinomas, four were p16 positive and five p16 negative. Neither patients who were HPV positive nor patients positive for p16 showed a significantly better outcome than HPV or p16 negative patients. In contrast, nicotine pack-years showed a highly significant correlation with survival in our patient collective. CONCLUSIONS: The data suggest that tumor stage and nicotine exposure seem to have the highest impact on survival in hypopharyngeal and laryngeal squamous cell carcinoma patients. There is no evidence for a better survival for p16 positive or HPV positive patients with hypopharyngeal or laryngeal squamous cell carcinoma. HPV seems to play a minor role in these entities of head and neck carcinoma.

Overexpression of DCLK1 is predictive for recurrent disease in major salivary gland malignancies.

Salivary gland carcinomas are a rare malignancy. Therefore, little is known about biomarkers and cancer stem cells in salivary gland malignancies. Double cortin-like kinase 1 (DCLK1) is a promising therapeutic target and cancer stem cell marker, predominantly investigated in pancreatic and colorectal cancer. The purpose of this study was to investigate the expression of DCLK1 in major and minor salivary gland carcinomas and its influence on survival. We examined a total of 80 patients with major or minor salivary gland cancer in this retrospective study. Immunohistochemistry with anti-DCLK1 antibody was applied to assess the expression of DCLK1. Moreover, we evaluated the impact of DCLK1 on overall and disease-free survival. DCLK1 expression could be detected in 66.3 % of all examined cases. Overexpression of DCLK1 was associated with reduced overall and disease-free survival in patients with major salivary gland cancer. Disease-free survival reached statistical significance (p = 0.0107). However, expression of DCLK1 had no influence on survival in patients with minor salivary gland cancer. Since treatment of recurrent disease in oncologic patients is utterly challenging, DCLK1 may be a promising prognostic biomarker that helps to identify patients with a high risk for recurrence of major salivary gland carcinoma.

The prognostic significance of ß-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: ß-catenin predicts overall survival.

Minor salivary gland carcinoma is a rare and heterogeneous type of cancer. Molecular prognostic and predictive markers are sparse. The aim of this study was to identify new prognostic and predictive markers in minor salivary gland carcinoma. 50 tissue samples of carcinomas of the minor salivary glands (adenoid cystic carcinoma n = 23, mucoepidermoid carcinoma n = 12, adenocarcinoma n = 10, carcinoma ex pleomorphic adenoma n = 2, salivary duct carcinoma n = 1, clear cell carcinoma n = 1, basal cell carcinoma n = 1) were immunohistochemically stained for ß-catenin, cyclin D1 and PIN1. Expression patterns were analyzed and correlated to clinical outcome of 37 patients with complete clinical data. High expression of membranous ß-catenin was linked to significantly better overall survival in patients with adenoid cystic carcinoma (log rank test, χ (2) = 13.3, p = .00397, Bonferroni corrected p = .024). PIN1 and cyclin D1 did not show any significant correlation to patients' clinical outcome. Expression of ß-catenin in adenoid cystic carcinoma of the minor salivary glands significantly correlates with better overall survival. Hence, evaluation of ß-catenin might serve as a clinical prognostic marker.

Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines.

BACKGROUND AND PURPOSE: Cafestol is a diterpene molecule found in coffee beans and has anticarcinogenic properties. The aim of the study was to examine the effects of cafestol in head and neck squamous cell carcinoma (HNSCC) cells. MATERIALS AND METHODS: Three HNSCC cell lines (SCC25, CAL27 and FaDu) were treated with increasing doses of cafestol. Then combination experiments with cisplatin and irradiation were carried out. Drug interactions and possible synergy were calculated using the combination index analysis. Clonogenic assays were performed after irradiation with 2, 4, 6 and 8 Gy, respectively, and the rate of apoptosis was measured with flow cytometry. RESULTS: Treatment of HNSCC cells with cafestol leads to a dose-dependent reduction of cell viability and to induction of apoptosis. Combination with irradiation shows a reduction of clonogenic survival compared to each treatment method alone. In two of the cell lines a significant additive effect was observed. CONCLUSION: Cafestol is a naturally occurring effective compound with growth-inhibiting properties in head and neck cancer cells. Moreover, it leads to a significant inhibition of colony formation.

Neurological Complications in Benign Parapharyngeal Space Tumors - Systematic Review and Meta-Analysis.

Introduction Parapharyngeal space tumors with complex anatomy and diverse histology have remained a challenging phenomenon for treating physicians. Objectives We have conducted a comprehensive web search on the PubMed, Web of Science, EMBASE, Cochrane Library, Biomedical Literature Database (CBM), and Clinicaltrials.gov databases to determine the factors that are associated with postoperative complications in parapharyngeal space tumors. Data Synthesis Two researchers reviewed all identified articles independently with a third reviewer for adjudication. Patient demographics and other clinicopathological characteristics were explored. The systematic review has identified 631 benign parapharyngeal space tumors with neurogenic and salivary tissue histology in 13 studies, with a mean age of 42.9 ± 7.76 years old and a median follow-up of 40.98 ± 19.1 months. Salivary gland (50.8%) and neurogenic (49.1%) tumors were the most common histological entities. Tumor size, location, histology, deep parotid lobe involvement, and proximity to great vessels or to the skull base were the deciding factors in selecting the surgical approach. The factors considered to select the surgical approach do not seem to have a correlation with the outcome in terms of neurological sequalae ( p = 0.106). Tumors with neurogenic histology have significantly increased chances of developing neurological complication (OR 6.07; p = 0.001). Conclusion Neurologic complications are significantly associated with neurogenic benign tumors rather than surgical approach.

P53 mutation is a rare event in Merkel cell carcinoma of the head and neck.

The aim of this retrospective analysis was to evaluate the status of p53 and possible mutations in Merkel cell carcinoma (MCC) cell lines and MCC tissue samples. The p53 mutations are common in different cancer origins but rare in MCCs detected so far. MCCs are highly aggressive neuroendocrine tumors with an enhanced potential to metastasize. Until now, less is known about MCC and new approaches to understand this disease are necessary. RNA and DNA were extracted from two MCC cell lines and 27 archival paraffin-embedded patient samples. After reverse transcription, a real-time PCR and a high-resolution melt analysis were carried out. In both MCC cell lines, we could detect a p53 missense mutation at codon 193 (exon 6) with a change in amino acids (His → Leu). This mutation was equal in both cell lines and was investigated in 27 tissue samples in succession to detect possible accounts for the aggressive behavior of MCCs. Unfortunately, no corresponding p53 mutation could be observed in the investigated tissue samples. A new p53 mutation was detected in MCC cell lines. This mutation could not be determined in patients' samples. Therefore, the aggressiveness of MCC seems to be independent of p53 mutations and other mutations might be responsible for developing MCC.

Impact of surgeons' experience and the single-shot perioperative antibiotic prophylaxis on outcome in stapedotomy.

BACKGROUND: The aim of this study was to evaluate whether surgeons´ experience and perioperative single-shot antibiotic prophylaxis affect outcome of patients undergoing stapes surgery. PATIENTS AND METHODS: We retrospectively evaluated audiological outcomes and postoperative complications of 538 consecutive patients who underwent stapes surgery at a single tertiary referral center between 1990 and 2017. Effects of different clinical variables, including single-shot antibiotic prophylaxis and surgeons' experience on outcome were assessed. RESULTS: 538 patients underwent 667 stapedotomies and postoperative complication rate was 7.5% (n = 50). Air conduction and air-bone gap closure improved significantly after surgery (14.2 ± 14.8 dB, p = 0.001; 14.5 ± 12.8 dB, p = 0.001). Multivariate analysis revealed that 6 years or less of surgical experience was independently associated with a higher incidence of persisting or recurrent conductive hearing loss (p = 0.033, OR 5.13) but perioperative application of antibiotics had no significant effect on outcome. CONCLUSION: First, clinical outcome regarding persisting or recurrent conductive hearing loss caused by incus necrosis and prosthesis luxation is linked to surgical performance. This underlines the need for a meticulous training and supervision of less experienced surgeons performing stapes surgery. Second, our results do not support the need for perioperative antibiotic prophylaxis in stapes surgery. Potential standard limitations of retrospective cohort studies (selection bias, confusion bias etc.) could play a role in interpreting our results. However, the probability for these limitations is minimized due to the large patient sample.

Intraparotid and cervical lymph nodes metastasis in primary parotid gland carcinoma-impact on clinical outcome.

OBJECTIVE: The aim of this study was to investigate the prognostic value of evaluation of intraparotid and cervical lymph node metastases in primary parotid cancer. STUDY DESIGN: A retrospective medical chart review and histopathologic evaluation of all patients surgically treated for primary parotid cancer during the period 1993 to 2010 was performed. The presence and ratio of intraparotid and cervical lymph node metastases were assessed and determined as primary predictor variables. Overall survival (OS) and disease-free survival (DFS) were defined as primary outcome variables. RESULTS: In total, 50 patients were included. The presence of pathologic cervical lymph nodes (P = .005) and a high cervical lymph node ratio (LNR) (P = .0001) had a significant association with worse OS. Worse DFS was found in patients with a high cervical LNR (P = .001) and intraparotid lymph node metastases (P = .029). In high-grade carcinoma, a high LNR showed worse DFS (P = .05). A high cervical LNR (P = .012) and resection margin status (P = .002) were identified as independent prognostic markers for OS and the presence of intraparotid lymph nodes for DSS (P = .05). CONCLUSIONS: Evaluation of patterns of lymph node metastases provides additional prognostic value in patients with primary parotid gland cancer.

Total versus subtotal tonsillectomy for recurrent tonsillitis - a prospective randomized noninferiority clinical trial.

Background: For many years experts have called for randomized controlled trials to resolve the question whether tonsillectomy, which is associated with significant comorbidity, can be replaced by partial tonsillectomy in patients with recurrent tonsillitis.Objective: To find out whether subtotal tonsillectomy is a suitable therapeutic alternative to total tonsillectomy in adult patients with recurrent episodes of acute tonsillitis.Material and methods: Study design - Single-blind prospective non-inferiority randomized clinical trial with intraindividual design. Setting - 80 patients were recruited at a tertiary referral center. Subjects - Adult patients with recurrent tonsillitis received total tonsillectomy on one side and subtotal tonsillectomy on the other side after randomization. Main outcome measure was frequency of postoperative tonsillitis on the side of subtotal tonsillectomy and postoperative pharyngitis in the former tonsil area on the side of total tonsillectomy. The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00015628).Results: Within 12 months none of the subjects suffered from recurrent tonsillitis after subtotal tonsillectomy. Subtotal tonsillectomy caused less pain than total tonsillectomy.Conclusion: Subtotal tonsillectomy might be an alternative treatment option associated with lower morbidity than total tonsillectomy in adults with recurrent tonsillitis.

Elective neck treatment in sinonasal undifferentiated carcinoma: Systematic review and meta-analysis.

Sinonasal undifferentiated carcinomas (SNUCs), being an aggressive malignancy with dismal survival outcome, have given limited consideration regarding management of regional failures. A total of 12 studies, published between 1999 and 2019, met inclusion criteria. We performed a meta-analysis assessing regional (neck) relapse after elective neck treatment compared to observation in clinically node negative (N0) necks. Clinical data of 255 patients were used for meta-analysis. Among them, 83.4% of patients presented with T4 tumors and 14.1% had positive neck nodes. Elective neck treatment was applied in 49.5% of analyzed patients. Regional relapses occurred in 3.7% of patients who have undergone elective neck treatment compared to 26.4% in patients who had not. Elective neck treatment significantly reduced the risk of regional recurrence (odds ratio 0.20; 95% confidence interval 0.08-0.49; P = .0004). The meta-analysis indicates that elective neck treatment could significantly reduce the risk of regional failures in patients with SNUCs.

Lymphoepithelial Carcinoma of Larynx and Hypopharynx: A Rare Clinicopathological Entity.

(1) Background: Lymphoepithelial carcinoma of the hypopharynx and larynx is a rare tumor with fewer than 50 cases in the published literature. We present a literature review to discuss the clinical findings, viral or genetic associations, diagnostic challenges, histopathological findings and therapeutic aspects of the disease. (2) Methods: A comprehensive literature review was performed through MEDLINE/PubMed from 1968 to 2018. We identified 21 studies comprising 46 patients. Data on all the clinicopathological features, diagnostic modalities, treatment options and viral or genetic etiology were extracted and analyzed using SPSS. (3) Results: The mean age of presentation was 64 years (range 40-82 years) and mostly involved males. The supraglottis and pyriform sinus were the most commonly involved sub-sites, with surgery as the preferred treatment modality. The presence of the Epstein-Barr virus possibly directs a viral etiology. The incidence of cervical and distant metastasis was 54% and 21%, respectively. The median survival time was 30 months. (4) Conclusions: Lymphoepithelial carcinoma of the hypopharynx is an aggressive tumor with a strong predilection for regional and distant metastasis. Surgery, in combination with adjuvant therapy, provides promising results. Immunohistochemistry helps in differentiating LEC from other pathologies.

ELMO3 - a Negative Prognostic Marker in Minor Salivary Gland Carcinoma.

Engulfment and cell motility 3 protein (ELMO3) is a protein that is involved in cell migration and promotes the remodeling of the cytoskeleton. Moreover, it is described as a prognostic marker in several cancers. The aim of this study was to evaluate ELMO3 expression in patients with minor salivary gland carcinoma. The expression of ELMO3 was examined by immunohistochemistry. The intensity of staining was evaluated and data was correlated to clinical outcome. Forty-six patients with complete clinical data were included into statistical analysis. ELMO3 expression was observed in 85% of the cases. High staining intensity of ELMO3 correlated with a significantly worse disease free survival (p = .0495) and a higher recurrence rate (p = .0071). In conclusion, it is still difficult to predict the clinical outcome of patients with minor salivary gland carcinoma. Evaluation of ELMO3 might serve as a clinical prognostic marker in future.

Neurological Complications in Benign Parapharyngeal Space Tumors - Systematic Review and Meta-Analysis

Abstract Introduction Parapharyngeal space tumors with complex anatomy and diverse histology have remained a challenging phenomenon for treating physicians. Objectives We have conducted a comprehensive web search on the PubMed, Web of Science, EMBASE, Cochrane Library, Biomedical Literature Database (CBM), and Clinicaltrials.gov databases to determine the factors that are associated with postoperative complications in parapharyngeal space tumors. Data Synthesis Two researchers reviewed all identified articles independently with a third reviewer for adjudication. Patient demographics and other clinicopathological characteristics were explored. The systematic review has identified 631 benign parapharyngeal space tumors with neurogenic and salivary tissue histology in 13 studies, with a mean age of 42.9 ± 7.76 years old and a median follow-up of 40.98 ± 19.1 months. Salivary gland (50.8%) and neurogenic (49.1%) tumors were the most common histological entities. Tumor size, location, histology, deep parotid lobe involvement, and proximity to great vessels or to the skull base were the deciding factors in selecting the surgical approach. The factors considered to select the surgical approach do not seem to have a correlation with the outcome in terms of neurological sequalae (p = 0.106). Tumors with neurogenic histology have significantly increased chances of developing neurological complication (OR 6.07; p = 0.001). Conclusion Neurologic complications are significantly associated with neurogenic benign tumors rather than surgical approach.

The effect of tonsillotomy on chronic recurrent tonsillitis in children.

OBJECTIVES: The objective of this study is to determine whether partial tonsillectomy (tonsillotomy) impacts the occurrence of acute or recurrent tonsillitis in children. METHODS: One hundred and eighty patients (1-14 years) were retrospectively surveyed by a questionnaire or by data analysis of a regional database. Subjects who suffered from severe systemic diseases or immunodeficiency syndromes were excluded. Episodes of acute tonsillitis before and after surgery, rate of antibiotic treatment, postoperative hemorrhage, and re-operation were obtained. RESULTS: Fifty-one patients suffered from preoperative tonsillitis. The rate of reinfection was 9.8%. The frequency of tonsillitis was significantly reduced in children after tonsillotomy (p < .001). Further, tonsillotomy led to a significant reduction of antibiotic treatment (p < .001). The rate of definitive tonsillectomy was 1.1% and thus effectiveness was very high. About 1.7% of all children suffered from postoperative bleeding, of which one (0.6%) required surgical revision. None of the bleedings was life threatening. CONCLUSIONS: Tonsillotomy is beneficial for patients with recurrent tonsillitis and carries less risk of postoperative complications than tonsillectomy.

A 5­year update of patients with HPV positive versus negative oropharyngeal cancer after radiochemotherapy in Austria.

BACKGROUND: After publishing promising results for the treatment of patients with human papilloma virus (HPV) positive oropharyngeal cancer with radiochemotherapy regarding 2­year survival, we present an update of the disease-specific and disease-free survival after 5 years. PATIENTS AND METHODS: A total of 29 patients of which 18 were HPV negative and 11 HPV positive with squamous cell carcinoma of the oropharynx received radiation therapy with or without chemotherapy (cisplatin) or immunotherapy (cetuximab) between 2007 and 2009. At time of the present analysis, six patients are still alive including four with HPV positive and two with HPV negative oropharyngeal carcinoma, while 15 out of 16 patients with HPV negative tumors died and 1 died of another cause with evidence of disease. RESULTS: Since the 2­year disease-specific survival of patients with HPV positive cancer of the oropharynx was published with 100% versus 30.4% in HPV negative tumors, we now present the 5­year disease-specific survival after treatment, which was 85.7% in HPV positive versus 11.1% in HPV negative patients. CONCLUSION: We present the results of patients receiving radiochemo(immuno)therapy for oropharyngeal cancer regarding the HPV status, which is still promising.

Sealing of the round and oval window niches with triamcinolone-soaked fascia as salvage surgical therapy in sudden sensorineural hearing loss.

CONCLUSIONS: Triamcinolone-soaked fascia seems to show better hearing improvement when added to tympanotomy for sudden idiopathic sensorineural hearing loss (SSHL), compared to fascia round window occlusion without triamcinolone. OBJECTIVES: To analyse if adding triamcinolone to sealing the round and oval window niches with fascia results in improved audiological outcome for acute SNHL. METHODS: Fifty-three patients (27m:43 ± 12 years, 26f:45 ± 14 years) with acute SSHL ≥50dB over 3 frequencies, who failed primary therapy, underwent transcanal tympanotomy. Twenty-five patients (Group A;cortisone:14m, 11f:46 ± 9 years) received sealing of the round and oval window with fascia soaked in triamcinolone (1ml; 40mg/ml) and 28 controls (Group B;no-cortisone:13m, 15f, 42 ± 12 years) without triamcinolone. Frequency specific and pure tone average (PTA =500-1000-2000-3000Hz) results were compared between Group A and B pre- and postoperatively. RESULTS: In Group A the PTA improved by ≥10dB in 21/25(83%) cases; in Group B 18/28(63%). Group A showed a statistically significantly better improvement across all frequencies, while linear regression revealed a significant decrease of posttherapeutic PTA to 94.96% of the initial PTA (p = .037). The overall PTA improved by 24dB. Group A improved from 73dB to 41dB(-32dB) PTA, Group B improved from 76dB to 56dB PTA (-20dB) (p < .05). Group A showed a significant additional decrease of 12.8dB (p < .001).

Correlation of ß-catenin, but not PIN1 and cyclin D1, overexpression with disease-free and overall survival in patients with cancer of the parotid gland.

BACKGROUND: Malignant tumors of the salivary glands comprise about 3% to 5% of all head and neck carcinomas. The purpose of our study was to find possible predictive and/or prognostic markers for parotid cancer. METHODS: A total of 46 tissue samples of carcinomas of the parotid gland were immunohistochemically stained for ß-catenin, cyclin D1, and PIN1. The factors were analyzed regarding their prognostic value for disease-free and overall survival. RESULTS: An overexpression of the cytoplasmatic ß-catenin was linked to a statistically significant worse outcome regarding disease-free (p = .0296) and overall survival (p = .0416). The 5-year overall survival was 83.9% in patients without and 0% in patients presenting with overexpression of cytoplasmatic ß-catenin. Additionally, Union Internationale Contre le Cancer (UICC) stage correlated with overall survival (p = .0306) and disease-free survival (DFS; p = .0473). CONCLUSION: Multivariate analysis showed that overexpression of cytoplasmatic ß-catenin and the UICC stage are 2 independent prognostic markers for survival in patients with parotid cancer.

Expression of ß-catenin and cyclin D1 in Merkel cell carcinomas of the head and neck.

BACKGROUND: Merkel cell carcinomas (MCC) are very aggressive tumors of the sun-exposed skin with a high potential to metastasize. Little is known about the genesis of MCC and very few prognostic markers have been detected so far. The Wnt pathway protein ß-catenin and the cell cycle protein cyclin D1 are two promotors of tumor growth and are expressed in a variety of malignant neoplasms such as lymphomas, thyroid, breast cancer, and many others. PATIENTS AND METHODS: Tissue samples of 27 patients with MCC were immunohistochemically stained for ß-catenin and cyclin D1 and correlated with overall survival of patients. In addition, western blot analysis was carried out in the two MCC cell lines MCC-13 and MCC-26. RESULTS: ß-catenin showed a cytoplasmatic expression of 10-30 % in 11 samples and an expression lower than 10 % in eight samples. Nuclear staining was visible in two samples. None of the 27 samples expressed cyclin D1. CONCLUSION: Neither cyclin D1 nor ß-catenin was expressed in a statistically significant manner, concluding that the development of MCCs is independent of ß-catenin and cyclin D1 expression and these proteins are not suitable as prognostic markers. We could describe the expression pattern of cyclin D1 for the first time.