APOS-antibiotic prophylaxis for preventing infectious complications in orthognathic surgery: study protocol for a phase III, multicentre, randomised, controlled, double blinded, clinical trial with two parallel study arms.

BACKGROUND: It is a constant debate among surgeons whether the use of prolonged postoperative antibiotics may reduce surgical site infection rates. As specific treatment guidelines are still lacking, many surgeons continue to use broad-spectrum antibiotics, causing not only increased costs but also contributing to the potential for antibiotic resistance. Hence, there is an urgent need for an appropriately designed prospective clinical trial, to investigate whether a prophylactic use of antibiotics after surgery actually decreases surgical site infections to a clinically relevant degree. METHODS: This study presents a multicentre, randomised, controlled, double-blinded, clinical trial with two parallel study arms to demonstrate that no postoperative antibiotic prophylaxis (AP) is not inferior to antibiotic prophylaxis with respect to surgical site infections in patients having undergone orthognathic surgery. The primary efficacy endpoint is defined as the occurrence of postoperative surgical site infections within 30 days of surgery. Secondary endpoints are further efficacy and subject-oriented parameters within 90 days after surgery. The entire trial is planned for 54 months, with an enrolment of 1420 patients over 39 months by 14 national participating centres. DISCUSSION: As a highly standardised procedure on an exceeding, healthy and young homogenous study population and identical processes all over the world, elective orthognathic surgery as clean-contaminated procedure provides comparable intervention groups with balanced baseline characteristics, comparable surgical duration, even when performed within multiple centres. Therefore, evaluating antibiotic prophylaxis after orthognathic surgery will be of high scientific value representable for other surgical procedures. TRIAL REGISTRATION: DRKS-German Clinical Trials Register- DRKS00022838 ; EudraCT No. 2020-001397-30. Registered on 29 March 2021.

Occurrence of cervical lymph node metastasis of maxillary squamous cell carcinoma - A monocentric study of 171 patients.

INTRODUCTION: Fewer than 5% of oral squamous cell carcinomas (SCC) are presented in the maxilla. The absence of cervical lymph node metastasis (LNM) is one of the main positive prognostic factors. This single-centre study analysed the cervical lymph node metastasis behaviour in patients with oral SCC of the upper jaw and serves as a basis for a cervical lymph node treatment suggestion. MATERIAL AND METHODS: The retrospective study includes 171 patients with isolated SCC of the maxilla. In addition to tumour resection, 83% of the patients underwent a selective neck dissection (ND). The data of cervical metastasis, TNM-status, tumour grade, tumour location as well as nicotine and alcohol behaviour were statistically analysed. RESULTS: The average rate of cervical metastasis was 44% in total. Tumour stage significantly affected risk for cervical metastasis (T1 = 6%, T2 = 41%, T3 = 60% and T4 = 60%) (p < 0.01). Development of cervical LNM was seemingly influenced by male gender. DISCUSSION: This study postulates a high rate of cervical metastasis of maxillary SCC. Risk for metastasis is mainly determined by the tumour stage. Alcohol and nicotine abuse have a negative impact on cervical LNM. CONCLUSION: Reviewing recent literature underlined by the illustrated data, we put up for discussion the treatment of SCC of the maxilla as similar to therapy protocols for SCC of the oral cavity. This would include an ipsilateral ND even in low tumour stage and in T4 staged tumours on both sides. However, prospective multicentre studies are needed to verify and recommend these therapy assumptions.

Oral health-related quality of life and depression/anxiety in long-term recurrence-free patients after treatment for advanced oral squamous cell cancer.

This report focuses on the association between oral health-related quality of life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients who were recurrence-free for 8 years after treatment for advanced oral squamous cell. Participants were 24 patients (mean age 55 years, 75% men) treated with neoadjuvant concurrent radiochemotherapy followed by surgery with a mean recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP) and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2). OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged correlation analysis, the correlation between OHRQoL to t1 and depression to t2 was significant and greater than the non-significant correlation for depression to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than vice versa. However, the difference in the correlation coefficients was not significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL measured with the OHIP was impaired in comparison to the normal population. In the limitations of the study design and bearing the small sample size in mind, the results give evidence that OHRQoL predicts psychological outcomes, namely depression and anxiety, better than vice versa.

The role of elective supraomohyoidal neck dissection in the treatment of early, node-negative oral squamous cell carcinoma (OSCC): a retrospective analysis of 122 cases.

The adequate treatment of the neck in early, clinically node-negative oral squamous cell carcinoma (OSCC) remains controversial. To assess whether elective supraomohyoid neck dissection is reasonable and efficient in early, locally circumscribed OSCC, the outcomes of treatment of 122 patients with an OSCC of clinical UICC stage I or II were retrospectively analysed in this study. Occult lymph node metastases were detected in 13.9% (17/122) of cases. They were more frequently found in T2 compared to T1 tumours (19.7% (14/71) vs. 5.9% (3/51), p=0.03), age, gender and grading had no influence on the prevalence of occult lymph node metastases (all p-values>0.05) in a multivariate logistic regression model. Subsequent multivariate survival analysis found that the presence of occult metastases was an independent predictor of reduced disease-free survival after 5 years (82.2% vs. 62.5%, p=0.004, and 61.9% vs. 17.8%, p<0.001, respectively). Elective supraomohyoid neck dissection detects occult metastases in early, node-negative OSCC, and patients with early OSCC exhibiting occult metastases should be considered as high risk patients, warranting additional therapeutic regimes.

Aberrant expression of p53, p16INK4a and Ki-67 as basic biomarker for malignant progression of oral leukoplakias.

BACKGROUND: 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, p16(INK4a), 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 p16(INK4a) 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/p16(INK4a)/Ki-67 aberration occurred in only three (9%) cases, of which two patients (66.7%) experienced progression to dysplasia and carcinoma in situ. The combined p53/p16(INK4a)/Ki-67 alteration had a negative predictive value (NPV) and sensitivity of 100%, specificity of 97% and positive predictive value (PPV) of 67%. By contrast, the combined p53/p16(INK4a)/Cyclin D1 alteration had 97% NPV and sensitivity of 50%, specificity of 90% and only 25% PPV. Loss of pRb and concomitant overexpression of p16(INK4a) were not observed arguing against an involvement of HPV in oral leukoplakia. CONCLUSIONS: We propose the combined p53/p16(INK4a)/Ki-67 alteration as a basic marker to define high risk leukoplakia patients. Lesions not showing this alteration appear to be harmless. Future studies should validate these findings and search for proteins which can further improve the PPV of the proposed basic marker.

Changes in the mandibular and dento-alveolar structures by the use of tooth borne mandibular symphyseal distraction devices.

PURPOSE: Different devices to perform a mandibular symphyseal distraction osteogenesis (MSDO) are available. This study evaluates how tooth borne distraction devices change to the teeth, the mandible and the condyles. MATERIALS AND METHODS: 19 patients (mean age 27.1) with anterior width deficiencies of the mandible were examined with routine pre- and postoperative CT-scans 1 month before and 4 months after a mean distraction width of 5.68 mm (SD 0.88). The anchorage teeth of the tooth borne device were examined concerning displacement of their axes as well as the movement of the condyles and the mandibular symphysis. The data were evaluated using Wilcoxon signed rank test and Spearman rho correlation. RESULTS: Significant tilting of the anchorage teeth was observed (p<0.01). The axes changed by 3.32° (SD 1.57) in the first premolar and by 2.63° (SD 1.75) in the first molar. A total of 2.67 mm (SD 1.17) of bone was formed on the symphysis. A significant correlation was found between distraction width and intercoronal distance changes of the anchorage teeth (p<0.01). No significant change of the intercondylar distance was found pre- and postoperatively in the Wilcoxon test. CONCLUSION: MSDO with tooth borne devices has strong effects on the anchorage teeth. No severe effects on the condyles were observed. The postoperative width gain is a result of newly generated bone in the symphysis and tooth tilting. Nevertheless stable postoperative bite corrections are achievable.

Comparative expressed sequence hybridization detects recurrent patterns of altered sequence expression in oral squamous cell carcinoma.

Despite its common histology and presentation, oral squamous cell carcinoma (OSCC) is associated with widely varying clinical behaviour and response to therapy. To further elucidate the molecular basis of OSCC, an approach for gene expression analysis termed comparative expressed sequence hybridization (CESH) was used in the present study. This straightforward approach allows the rapid delineation of pathophysiologically interesting candidate chromosome regions by a direct detection of aberrant transcriptional activation. CESH profiling of OSCC specimens led to the identification of several novel chromosomal regions. Increased expression compared to a set of control mucosa specimens was found on 1q22-q23, 3q26.3-qter, 4q31.1-q32, 11q12-q13.2, 14q32, 18q12, 19q13.2-q13.3 and 22q13.1-q13.2. Decreased expression was found on 8p22-p23, 16p12 and 16q23-q24. Using CESH, common patterns of altered sequence expression in different OSCC samples were obtained. While some of these regions overlap with those known to be frequently altered in OSCC on the genomic level, this screen revealed novel chromosome subregions with increased transcriptional activity, which are probably independent of the genomic status of the tumor cells.

Haemangiopericytoma of the mandible.

Haemangiopericytomas (HPCs) found in bony structures are rare sarcomas of vascular origin. Here, we report the case of a 41-year-old female with a HPC originating in the right ramus of the mandible. After tumour staging and biopsy for histological reference the tumour was surgically removed. The surgical technique is described and therapy options of these rare cases are discussed and compared with these cases already documented. To the best of our knowledge, this is the 6th case of mandibular HPC reported in the literature.

Cytogenetic characterization of head and neck squamous cell carcinoma cell lines as model systems for the functional analyses of tumor-associated genes.

Head and neck squamous cell carcinoma (HNSCC) is a solid malignant neoplasm exhibiting aggressive phenotypes and high recurrence rates. To improve its clinical management, understanding the molecular basis of HNSCC development is of critical importance. For the investigation of tumor-associated genes, functional analyses in well-characterized tumor cell systems are required. To establish an experimental platform, a set of 20 HNSCC cell lines was screened for genetic imbalances by chromosomal comparative genomic hybridization (cCGH). Frequent DNA copy number gains were detected on 3q26.3-qter, 5p, 7p11-p13, 8q23-qter, 9p11-p13, 9q31-qter, 11q13 and 20q13.1, whereas copy number losses were found on 3p, 4p, 4q32.1-qter, 8p11-p12 and 18q22 in agreement with previous observations on genetic aberrations detected in primary HNSCC specimens. Subsequent mRNA expression analysis of 11q13 candidate genes CCND1 and CTTN revealed that HNSCC cell lines exhibiting a DNA copy number gain on 11q13 had a higher transcript level of CCND1 and CTTN compared with HNSCC cell lines without 11q13 copy number gain (P = 0.014 and P = 0.009, respectively). Furthermore, CCND1 and CTTN amplification as detected by fluorescence in situ hybridization correlated with protein expression as assessed by immunocytochemistry. In summary, the cytogenetic characterization illustrates that this set of HNSCC cell lines is representative for the HNSCC genome and provides tumor model systems for detailed analysis of genes with a possible role in the pathomechanism of head and neck tumors.

Recurrent copy number gain of transcription factor SOX2 and corresponding high protein expression in oral squamous cell carcinoma.

Gene copy number aberrations are involved in oral squamous cell carcinoma (OSCC) development. To delineate candidate genes inside critical chromosomal regions, array-CGH was applied to 40 OSCC specimens using a microarray covering the whole human genome with an average resolution of 1 Mb. Gene copy number gains were predominantly found at 1q23 (9 cases), 3q26 (11), 5p15 (13), 7p11 (7), 8q24 (17), 11q13 (15), 14q32 (8), 19p13 (8), 19q12 (7), 19q13 (8), and 20q13 (9), whereas gene copy number losses were detected at 3p21-3p12 (15), 8p32 (11), 10p12 (8), and 18q21-q23 (10). Subsequent mRNA expression analyses by quantitative real time polymerase chain reaction found high mRNA expression of candidate genes SOX2 in 3q26.33, FSLT3 in 19p13.3, and CCNE1 in 19q12. Tissue microarray (TMA) analyses in a representative OSCC collection found gene copy number gain for SOX2 in 52% (115/223) and for CCNE1 in 31% (72/233) of the tumors. Immunohistochemical analyses on TMA sections of the corresponding proteins detected high expression of SOX2 in 18.1% (49/271) and of CyclinE1 in 23.3% (64/275) of tumors analyzed. These findings indicate that SOX2 and CCNE1 might be activated via gene copy number gain and participate in oral carcinogenesis. The combination of array-CGH with TMA analyses allows rapid pinpointing of novel promising candidate genes, which might be used as therapeutic stratification markers or target molecules for therapeutic interference.

High 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) uptake measured by positron emission tomography is associated with reduced overall survival in patients with oral squamous cell carcinoma.

Patients with oral squamous cell carcinoma (OSCC) and poor prognosis may benefit from an intensification of the initial therapy scheme. To improve the clinical management of these patients, there is a strong requirement for an accurate assessment of the malignant properties of the individual lesion. The objective of the present analysis was to define the potential value of 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) uptake in the tumor measured by positron emission tomography (PET) in predicting patients' outcome in the clinical course of OSCC. In this respect, a clinically well-defined cohort of 79 patients with primary OSCC was retrospectively evaluated. (18)FDG uptake in the primary tumor site was quantified by calculation of the maximum standardized uptake values (SUV(max)). Subsequent statistical analyses found, that (18)FDG uptake of the primary tumor was significantly higher in stage T3/T4 vs. T1/T2 (p<0.001), in UICC stage IV vs. stage I-III (p=0.01), and in N1-3 vs. N0 tumors (p<0.001), respectively. To define SUV(max) cut-off values for survival analyses, receiver operating curves (ROC) were calculated for overall and disease-free survival after 36 and 60 months, respectively. Univariate survival analysis showed that high SUV(max) was significantly associated with shortened overall survival after 36 (p=0.026) and 60 months (p=0.02). Subsequent multi-variate Cox regression analysis including SUV(max), age, gender and UICC stage as co-variables determined that, high SUV(max) was the only predictor of inferior overall survival after 60 months (p=0.035) in this model. In conclusion, (18)FDG uptake detected by PET predicts adverse outcome of patients with OSCC in this retrospective analysis. (18)FDG-PET might be a promising tool to contribute to therapeutic decisions and should be evaluated in future prospective studies.

Clinical use of navigation based on cone-beam computer tomography in maxillofacial surgery.

Image-guidance in maxillofacial surgery is based predominantly on computed tomographic (CT) images. Its main disadvantage is the considerable amount of radiation to which the patient is exposed, and dental metal artefacts. Recently, a new class of devices based on the concept of cone-beam computed tomography (CBCT) has been introduced for maxillofacial imaging, which we have investigated. In a clinical study, the first seven patients to be operated using a navigation system based on CBCT images, were evaluated. In all cases patient to image recording was uneventful and the surgical objective was reached. The guidance given by the navigation system was helpful. CBCT is an alternative to conventional CT, gives a lower dose of radiation, and costs less. Limitations in the quality of the images and the size of the field of view may restrict its use. It is suitable for image-guided surgery using a navigation system as long as the images show enough of the relevant anatomy and pathology.

Recurrent craniofacial dermatofibrosarcoma protuberans: long-term prognosis after close surgical removal.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant neoplasm of the dermis that rarely manifests in the craniofacial area. In this retrospective analysis, we investigated the long-term survival of 7 patients with recurrent craniofacial DFSP. This study includes all patients in our department with recurrences of DFSP between 1989 and 2006. All patients were treated by radical surgery with 1-cm free safety margin in every direction and remained in routine long-term follow-up for tumor patients. Two of the 7 patients showed a local recurrence, which was again successfully treated surgically with the same technique. Advanced reconstruction with free full-thickness skin transfers, regional flaps, and forearm flaps, respectively, was required in 5 of the 7 patients. The other 2 patients were reconstructed locally. The long-term prognosis of craniofacial DFSP can be assessed optimistically even if the tumor already reoccurred. All 7 patients included in this study are still alive and so far not suffering from local recurrence. Advanced reconstructive techniques are often required in the management of reoccurring craniofacial DFSP. Late recurrences have been reported; therefore, a long-term follow-up for these patients should be considered.

Activation of MAP kinase signaling through ERK5 but not ERK1 expression is associated with lymph node metastases in oral squamous cell carcinoma (OSCC).

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, subsequent tissue microarray analyses by immunohistochemistry revealed an increase in protein expression of MAP kinase-related proteins ERK1 in 22.8% (48 of 209) and ERK5 in 27.4% (76 of 277), respectively. An association of high ERK5 but not of high ERK1 expression with advanced tumor stage and the presence of lymph node metastases was found (P = .008 and P = .016, respectively). Our analysis demonstrates the reliability of the combined approach of gene expression profiling, signaling pathway analyses, and tissue microarray analysis to detect novel distinct molecular aberrations in OSCC.

Interdisciplinary combined treatment of craniofacial osteosarcoma with neoadjuvant and adjuvant chemotherapy and excision of the tumour: a retrospective study.

Osteosarcomas are highly malignant tumours of bone, and are rare in the craniofacial area. They account for only 1% of all head and neck malignancies. In this study we describe the treatment of 12 patients who were diagnosed with osteosarcoma of the mandible or maxilla between 1990 and 2004. These patients were given interdisciplinary treatments, either with a combination of neoadjuvant and adjuvant high-dose chemotherapy following the protocol of the cooperative osteosarcoma study group (COSS) with radical excision of the tumour (n=7), with a combination of radiation and radical excision (n=2), or with radical excision alone of the tumour (n=3). The 5-year survival of the group treated only by excision was 1 of 3, whereas that of the group treated by combination of chemotherapy and surgical removal was 7 of 7. The two patients treated with radiation and excision also lived 5 years after the end of the treatment, but had side-effects of radiation, whereas those treated with chemotherapy had no serious side-effects. We therefore conclude that combined interdisciplinary treatment of radical resection of the tumour with high-dose chemotherapy according to standard protocols is the most effective treatment for craniofacial osteosarcomas.

Neoadjuvant concurrent radiochemotherapy followed by surgery in advanced oral squamous cell carcinoma (OSCC): a retrospective analysis of 207 patients.

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<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.

Frequent high telomerase reverse transcriptase expression in primary oral squamous cell carcinoma.

BACKGROUND: Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC. METHODS: Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC). RESULTS: Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P < 0.001). By contrast, specific TERT amplifications were less common in OSCC (2.1%, 4/191) compared with PSCC/LSCC (9.9%, 8/81) (P = 0.047). CONCLUSIONS: High hTERT expression is a frequent finding in OSCC. It might be a promising target for the development of specific anti-neoplastic therapy approaches.

A large ameloblastic fibro-odontoma of the right mandible.

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.

High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy.

Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p > 0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy.

Recurrent FGFR1 amplification and high FGFR1 protein expression in oral squamous cell carcinoma (OSCC).

Chromosomal aberrations are known to have an impact on the initiation and progression of oral squamous cell carcinoma (OSCC), but individual genes involved in OSCC pathogenesis are poorly described. To elucidate the molecular events underlying oral carcinogenesis, a set of primary OSCC were screened for distinct genetic imbalances by means of array-based comparative genomic hybridisation. For this, a DNA array was used containing 812 genomic targets including oncogenes, tumour-suppressor genes and chromosomal regions frequently altered in human neoplasms. The most frequent aberrations were amplification of MYC, EGFR, CCND1 and PIK3CA, whereas deletions affected TRAILR1 and ATM. Furthermore, a distinct high-level amplification of the fibroblast growth factor receptor 1 (FGFR1) locus was detected in two cases. Detailed FISH analysis on OSCC tissue microarray sections revealed amplification prevalence for FGFR1 of 17.4% (16/92). Furthermore, FGFR1 protein analysis by immunohistochemistry on a TMA containing 178 OSCC found a high FGFR1 expression in tumours of early t-stadium and UICC stage (T1/2 vs. T3/4: p=0.002; SI-II vs. S III-IV: p=0.048). Our results indicate that an increase in FGFR1 expression contributes to oral carcinogenesis at an early stage of development.