Papers by Christof Hofele
The ameloblastic fibro-odontoma is a rare mixed odontogenic tumor. It occurs predominantly in chi... more The ameloblastic fibro-odontoma is a rare mixed odontogenic tumor. It occurs predominantly in children and young adults with no sex predilection and locates most often in the posterior segment of the mandible. A painless swelling is the most common clinical sign. Radiologically, ameloblastic fibro-odontoma shows a circumscribed radiolucency, which contains radio-opaque foci of various sizes and shapes. Histological examination reveals
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Laryngo-Rhino-Otologie
p53 gene aberrations are the most common genetic changes seen in human carcinogenesis. Frequently... more p53 gene aberrations are the most common genetic changes seen in human carcinogenesis. Frequently, single point mutations are detected, resulting in increased levels of (an aberrant) p53 protein in tumor cells. The cellular protein produced appears to become immunogenic during tumor development, inducing the production of circulating antibodies against p53. For this study, sera from 126 patients with oral squamous cell carcinomas (102 primary tumours and 24 recurrent/secondary tumours) were examined for p53 autoantibodies and their further clinical course was followed up for more than 5 years. 80 sera from internal medicine patients without known or suspected neoplasm served as control. A sandwich ELISA (enzyme linked immuno sorbent assay) designed by Dianova, Hamburg was used to detect p53 autoantibodies. In 18.6 % of the patients with primary oral squamous cell carcinomas, p53 autoantibodies were detected, and also in 50 % of the patients with recurrent or local secondary carcinom...
In an attempt to further elucidate the pathomechanisms in oral squamous cell carcinoma (OSCC), ge... more In an attempt to further elucidate the pathomechanisms in oral squamous cell carcinoma (OSCC), gene expression profiling was performed using a whole-transcriptome chip that contains 35,035 gene-specific 70mere oligonucleo- tides (Human OligoSet 4.0; Operon, Cologne, Germany) to a set of 35 primary OSCCs. Altogether, 7390 genes were found differentially expressed between OSCC tumor samples and oral mucosa. To characterize the
Fluorescence in situ hybridization was applied on a collection of 609 squamous cell carcinomas of... more Fluorescence in situ hybridization was applied on a collection of 609 squamous cell carcinomas of the head and neck (HNSCCs), including 511 primary carcinomas of different clinical stage and anatomical localization and 98 recurrent carcinomas, second primary carcinomas, and regional metastases on a tissue microarray. The overall prevalence of amplifica- tions of five oncogenes analyzed was 34.5% for CCND1, 12.7%
British journal of cancer, Jan 28, 2005
Overrepresentation of chromosomal bands 3q25-q29 has been associated with shortened disease-speci... more Overrepresentation of chromosomal bands 3q25-q29 has been associated with shortened disease-specific survival in head and neck squamous cell carcinoma (HNSCC). To assess the prevalence of copy number gains (>4 signals per cell) and high-level amplifications (>8 signals per cell) from putative oncogenes in this chromosomal region (CCNL1, SNO, PIK3CA, TP73L), tissue microarray analysis was applied on 280 HNSCCs by fluorescence in situ hybridization. Overall frequency of additional copy numbers was 34.3% for CCNL1, 31.8% for SNO, 39.0% for PIK3CA and 38.3% for TP73L, respectively. In general, gains were more frequently detected in stage IV compared to stage I-III tumours. Performing multivariate logistic regression analysis, a significant association of CCNL1 gains and the presence of lymph node metastases was found, which was independent of anatomical site and T-stage of the primary tumour (P=0.049). Site-specific subgroup analysis further showed that copy number gains of CCNL1 ...
Mund-, Kiefer- und Gesichtschirurgie : MKG, 2002
Oral squamous cell carcinomas (OSCC) are malignant tumors with a poor prognosis and low long-term... more Oral squamous cell carcinomas (OSCC) are malignant tumors with a poor prognosis and low long-term survival rates, even when using modern adjuvant and neoadjuvant therapy forms in addition to surgery. For the clinical estimation of each tumor, it is necessary to define stage-dependent molecular and/or cellular parameters as it is known that OSCC develop along a multistep pathway including the loss of tumor suppressor genes and the amplification of oncogenes which result in changes in protein expression. In order to establish a reliable pattern of molecular and cellular biomarkers, a large number of tumor specimens from different stages of the disease need to be analysed. In this study, biopsies of a collective of 293 OSCC in different stages were screened with the novel technique of tissue chip microarrays by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). FISH-analysis was performed on the oncogene cyclin D1 and IHC-analysis on the proteins cyclin D1, p53, ...
Medicina oral, patología oral y cirugía bucal, 2007
The ameloblastic fibro-odontoma is a rare mixed odontogenic tumor. It occurs predominantly in chi... more The ameloblastic fibro-odontoma is a rare mixed odontogenic tumor. It occurs predominantly in children and young adults with no sex predilection and locates most often in the posterior segment of the mandible. A painless swelling is the most common clinical sign. Radiologically, ameloblastic fibro-odontoma shows a circumscribed radiolucency, which contains radio-opaque foci of various sizes and shapes. Histological examination reveals a fibrous soft tissue, islands of odontogenic epithelium and a disordered mixture of dental tissues. The tumor produces enamel or enamel matrix, dentin and cementum. The treatment of ameloblastic fibro-odontomas usually consists of enucleation or surgical curettage, which is possible due to their benign biological behaviour.
Oral Oncology Supplement, 2007
Oral and Symposium abstracts, Friday 18 May development of an oral-cutaneous fistula, skin necros... more Oral and Symposium abstracts, Friday 18 May development of an oral-cutaneous fistula, skin necrosis or the need for a second reconstructive procedure as having had a significant affect on outcome (p < 0.05). Conclusion: MVFF reconstruction following the surgical treatment of advanced ORN results in successful outcomes for the majority of patients despite frequent complications.
Oral Oncology Supplement, 2007
International Journal of Oral and Maxillofacial Surgery, 2005
Oral Presentations / 0 14. Reconstructive Surgery I rate of the tumor-free survival was higher in... more Oral Presentations / 0 14. Reconstructive Surgery I rate of the tumor-free survival was higher in the BVM+ group (77%) than in the BVM group (55%). Based on the better histological result and higher tumor-free survival rate in the BVM+ group, we recommend the adjuvant use of Culevit tablets in BVM chemotherapy of oro-pharyngeal squamous-cell cancer to increase further the efficacy of treatment in preventing the recidivism.
Neoplasia (New York, N.Y.)
In an attempt to further elucidate the pathomechanisms in oral squamous cell carcinoma (OSCC), ge... more In an attempt to further elucidate the pathomechanisms in oral squamous cell carcinoma (OSCC), gene expression profiling was performed using a whole-transcriptome chip that contains 35,035 gene-specific 70 mere oligonucleotides (Human OligoSet 4.0; Operon, Cologne, Germany) to a set of 35 primary OSCCs. Altogether, 7390 genes were found differentially expressed between OSCC tumor samples and oral mucosa. To characterize the major biologic processes in this tumor collection, MAPPFinder, a component of GenMAPP version 2.1, was applied to this data set to generate a statistically ranked list of molecular signaling pathways. Among others, cancer-related pathways, such as mitogen-activated protein (MAP) kinase signaling (z score = 4.6, P < .001), transforming growth factor-beta signaling (z score = 3.0, P = .015), and signaling pathways involved in apoptosis (z score = 2.1, P = .037), were found deregulated in the OSCC collection analyzed. Focusing on the MAP kinase signaling pathway,...
Journal of Oral Pathology and Medicine
J Oral Pathol Med (2011) 40: 629–635Background: The risk of malignant progression of oral leukopl... more J Oral Pathol Med (2011) 40: 629–635Background: The risk of malignant progression of oral leukoplakia with and without dysplasia is unpredictable.Materials and methods: Leukoplakias without dysplasia of 35 patients, leukoplakias with dysplasia of 4 patients, and similar lesions obtained from tumor patients were retrospectively examined by immunohistochemistry for the expression of the proteins pRb, p53, p16INK4a, Cyclin D1 and Ki‐67. The predictive power of combined aberrant expression patterns for the progression of leukoplakias without dysplasia was examined.Results: Increased expression of p53, Ki‐67 and Cyclin D1, and loss of p16INK4a occurred in 45.9%, 38.9%, 29.4% and 32.4% of the leukoplakias without dysplasia, respectively. All alterations increased with progression but had poor positive predictive value. However, the combined p53/p16INK4a/Ki‐67 aberration occurred in only three (9%) cases, of which two patients (66.7%) experienced progression to dysplasia and carcinoma in s...
Laryngo-Rhino-Otologie, 2002
International Journal of Oral and Maxillofacial Surgery, 2005
Mund-, Kiefer- und Gesichtschirurgie, 1997
Zusammenfassung Robotiksysteme befinden sich bei stereotaktischen neurochirurgischen Eingriffen ... more Zusammenfassung Robotiksysteme befinden sich bei stereotaktischen neurochirurgischen Eingriffen sowie orthopädischen Eingriffen im Hüftgelenk-oder Kniebereich in der fortgeschrittenen Erprobung oder kurz vor der kommerziellen Einführung. Neben diesen aus der Makrorobotik stammenden Beispielen wird auf dem Gebiet der Mikrorobotik und Mikrosystemtechnik an fortgeschrittenen aktiven Endoskopiesystemen für die minimalinvasive Chirurgie gearbeitet. Im Gegensatz zu den meisten industriellen Werkstücken sind in der Medizin die zu
HNO, 2008
Keratocystic odontogenic tumors are benign neoplasms of the viscerocranium that occur sporadicall... more Keratocystic odontogenic tumors are benign neoplasms of the viscerocranium that occur sporadically as well as in association with Gorlin-Goltz syndrome. Multiple basal cell carcinomas of the skin are another typical feature of Gorlin-Goltz syndrome. Aberrant activation of sonic hedgehog signaling has been reported for sporadic and hereditary basal cell carcinoma caused by specific genetic mutations, but for keratocystic odontogenic tumors, the role of aberrant sonic hedgehog signaling has not yet been evaluated in detail. In the present study, 131 keratocystic odontogenic tumors were analyzed by immunohistochemistry for the expression of sonic hedgehog signaling proteins SHH, PTCH1, SMO, GLI1, and NMYC on tissue microarray sections. High expression of the analyzed proteins-between 67.3% (PTCH1) and 92.9% (SHH)-was found in the epithelial compartment of the keratocystic odontogenic tumors analyzed. In the stromal compartment of the tumors, high expression of the target proteins was found significantly less frequently (all p-values &lt;0.001). Aberrant sonic hedgehog signaling is critically involved in the molecular pathogenesis of keratocystic odontogenic tumors. This finding underlines the neoplastic character of this intraosseous lesion. Because of high recurrence rates after local excision, more radical surgical approaches are recommended for treating keratocystic odontogenic tumors.
Mund- Kiefer- und Gesichtschirurgie
The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrea... more The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradioth...
Oral and Maxillofacial …, 2002
... Die simultane Radiochemothera-pie erhöht sowohl die lokale Tumorkon-trolle als auch das krank... more ... Die simultane Radiochemothera-pie erhöht sowohl die lokale Tumorkon-trolle als auch das krankheitsfreie Über-leben sowohl nach konventioneller Fraktionierung ... 1. Becker A, Buechele T, Sandner A, Haensgen G, Schoeber C, Mir-Salim P, Berghaus A, Dunst J, Schmoll HJ ...
Oral Oncology, 2005
Adenoid cystic carcinoma (ACC) of the salivary gland is characterized by a prolonged but inevitab... more Adenoid cystic carcinoma (ACC) of the salivary gland is characterized by a prolonged but inevitably unfavorable clinical course. Recent studies suggested the transmembrane tyrosine kinase KIT to be involved in ACC pathogenesis. To investigate KIT expression in histologically defined subgroups of ACC and to clarify whether KIT gene copy number gain contributes to KIT overexpression, tumor tissue microarray sections including 55 ACC tumors were analyzed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The prevalence of positive KIT immunostaining was 89% (49/55). Strong immunostaining of KIT was only found in cribriform and tubular but never in solid subtypes (p=0.02). Average KIT staining intensity was higher in cribriform and tubular (n=37) compared to solid (n=18) ACC subtypes (p=0.005). FISH analysis revealed copy number gains of the KIT gene in 6.1% (3/49) of tumors analyzed. Our results implicate that specific KIT tyrosine kinase inhibitors such as imatinib, might be used in future therapeutic approaches against subgroups of ACC.
Oral Oncology, 2008
Locally advanced operable oral squamous cell carcinoma (OSCC) continues to be a major therapeutic... more Locally advanced operable oral squamous cell carcinoma (OSCC) continues to be a major therapeutic challenge despite the implementation of novel multi-modal treatment approaches. To improve local and local-regional control and to allow functional reconstruction after ablative surgery, neoadjuvant protocols have been developed during the last decade implementing radiochemotherapy prior to selective surgery. In the present retrospective analysis, the results of concurrent radiotherapy with 40 Gy and low-dose cisplatin-based chemotherapy followed by major surgery are presented for n=207 patients with an OSCC of stage III or IV. The overall survival for all patients analyzed was 49.5% after 60 months and 37.0% after 120 months. Further subgroup analysis found that histopathologic N0 tumours had a significantly better 5-year and 10-year overall survival rate than N+ tumours (p=0.004). In multivariate analysis, only postoperative N0 stage was a significant predictor for a favourable outcome (p=0.004). Overall disease-free survival of the whole patient collective was 70.4% after 60 months and 62.6% after 120 months with superior 60 month and 120 month disease-free survival for T0 (p=0.018) and N0 tumours (p=0.007), which was verified by multivariate analysis (p=0.019 and p=0.055, respectively). T+ tumours inherited a 2.5-fold increased risk for the development of local or loco-regional failure (p=0.05), and N+ tumours a 6.1-fold increased risk for the development of distant metastases (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). In conclusion, neoadjuvant radiochemotherapy with 40 Gy and concurrent low-dose cisplatin monotherapy followed by selective surgery is a feasible and reliable therapy concept, which results in encouraging overall and disease-free survival rates for therapy responders and which reliably selects therapy non-responders by the histopathological assessment of the neck dissection preparation. Those therapy non-responders might profit from intensified systemic therapy approaches.
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Papers by Christof Hofele