Search

Background: Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the polycomb repressive complex 2, plays an important role in tumor development and progression by interacting with histone and non-histone proteins. EZH2 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types., Material and Methods: This study investigates the prognostic relevance of immunohistochemical EZH2 expression in head and neck squamous cell carcinoma. Tissue microarray sections with 667 cancers of oral cavity, oro- and hypopharynx and larynx were analyzed for EZH2 expression., Results: Nuclear EZH2 staining was recorded in 322 (81.8%) of 394 cases. Staining was weak in 33 (10.2%), moderate in 128 (39.6%), and strong in 103 (32.0%) cancers. The prevalence of EZH2 expression in tumors of the oral cavity and the orohypopharynx was higher as compared to cancers of the larynx (P = .0023). EZH2 expression was correlated to presence of lymph node metastasis (P = .0089) but was unrelated to histological grade, tumor stage, surgical margin, or distant metastasis. EZH2 expression had no impact on patient survival., Conclusion: The high prevalence of EZH2 expression in head and neck squamous cell carcinoma stresses its capability as a therapeutic target., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: βIII-tubulin (TUBB3) is an isotype of microtubules, which are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, and mitosis. Overexpression of TUBB3 was found to be associated with poor prognosis and resistance to tubulin-binding drugs and in several solid tumors including head and neck squamous cell carcinomas (HNSCC). Considering the potential high importance of a prognostic biomarker in these cancers, this study aimed to investigate the clinical relevance of immunohistochemical TUBB3 expression in HNSCC., Methods: Tissue microarray (TMA) sections containing samples from 667 cancers of oral cavity, oro- and hypopharynx, and larynx for which follow-up data were available were analyzed for TUBB3 expression by immunohistochemistry., Results: Over 90% of our analyzed cancers showed unequivocal cytoplasmic TUBB3 expression. Staining was considered weak in 69 (15.5%), moderate in 149 (33.5%), and strong in 188 (42.2%) of cancers. The frequent TUBB3 overexpression showed no significant correlation with pathological grading, tumor stage, nodal status, or surgical margin and had no impact on patient outcomes., Conclusion: Despite lacking prognostic utility in HNSCC, the remarkable high prevalence of TUBB3 expression in HNSCC emphasizes its putative relevance as a target for future drugs targeting TUBB3., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: CD151 is a plasma membrane protein belonging to the tetraspanin family. CD151 represents a putative therapeutic target and has been suggested as a prognostic marker in several cancer types. The present study aims to investigate the prognostic relevance of immunohistochemical CD151 expression in head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: Tissue microarray (TMA) sections containing samples from 667 cancers of oral cavity, oro- and hypopharynx and larynx, for which follow-up data were available, were analyzed for CD151 expression by immunohistochemistry., Results: Membranous CD151 immunostaining was recorded in 269 (60.3 %) of 446 analyzable cases. Staining was considered weak in 129 (28.9 %), moderate in 98 (22.0 %), and strong in 42 (9.4 %) of cancers. CD151 expression was unrelated to histological grade, tumor stage, nodal status, or surgical margin. There was a tendency towards a somewhat lower prevalence of CD151 expression in tumors of the oral cavity (52.9 % positive) as compared to cancers of the oro-hypopharynx (62.1 %) and larynx (63.3 %; p = 0.0100). CD151 expression had no impact on patient survival., Clinical Relevance: In summary, immunohistochemical analysis of CD151 lacks prognostic utility in HNSCC. The high prevalence of CD151 expression in HNSCC emphasizes its putative relevance as a therapeutic target for further development of anti-CD151 drugs.

A novel technique to reduce donor site morbidity after radial forearm free flap (RFFF) harvest, using a local full-thickness skin graft (FTSG), is described. Thirty consecutive patients undergoing RFFF for head and neck reconstruction were enrolled in a prospective study. Donor site defect closure was performed with spindle-shaped FTSGs excised from the wavelike skin incision made for the vascular pedicle. Both the removal site of the FTSG on the volar forearm and the covered RFFF donor site healed uneventfully in 29 cases, with no impairment of function related to the skin graft. No skin graft failure and no exposure, tenting, or adherence of the flexor tendons occurred. All patients expressed satisfaction with postoperative pain, the functional outcome, and cosmetic appearance. Primary donor site defect closure could be achieved in all cases with the use of a local FTSG. This graft can be gained at the access incision for the vascular pedicle, avoids expansion of the incision for a local flap technique, and does not prolong wound healing, and thus reduces both donor site and graft site morbidity of the RFFF. This technique leads to an inconspicuous aesthetic result with no apparent relevant functional deficits and avoids the need for a second donor site., (Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed in a number of malignancies (e.g. prostate, breast, squamous cell carcinoma of the esophagus, lung and head and neck tumors). Based on studies in which ALCAM showed prognostic relevance in several carcinomas, it has been discussed as a potential therapeutic target. We evaluate its expression in head and neck squamous cell carcinomas (HNSCCs). A tissue microarray was constructed from more than 400 HNSCCs. Slides were analyzed by immunohistochemistry for ALCAM. Membranous and cytoplasmic ALCAM positivity were rated separately. The tumors were combined into (a) cases with membranous staining and (b) cases with cytoplasmic staining, independently from membranous/cytoplasmic co-expression. We found staining in 70.3% of interpretable HNSCCs. Pure membranous staining was found in 12.4% of tumors, with cytoplasmic positivity in 40.1% of cases, and membranous/cytoplasmic co-expression in 17.9%. No significant association between ALCAM positivity and clinical parameters was found. No significant association between ALCAM expression and survival data was observed for all tumors. The frequent expression of ALCAM (70.3%) in head and neck squamous cell carcinomas does not support an important role for HNSCC biology. The increased levels of ALCAM suggest the existence of a therapeutic window for potential anti-ALCAM therapies., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p < 0.0001), 46.6 versus 50.0 versus 109.0 for MAGE-A3/A4 (p = 0.0074) and 13.3 versus 50.0 versus 100.2 months for NY-ESO-1 (p = 0.0019). By multivariate analysis, these factors were confirmed as independent markers for poor survival. HNSCC patients showing protein expression of MAGE-A family members or NY-ESO-1 represent a subgroup with an extraordinarily poor survival. The development of immunotherapeutic strategies targeting these CTA may, therefore, be a promising approach to improve the outcome of HNSCC patients., (© 2014 UICC.)

In a total of 171 surgical procedures for lesions in the head and neck region in patients in whom phenprocoumon therapy was not stopped, 16 (9%) postoperative bleeding events were observed over a follow-up period of two weeks. Local measures were sufficient in all cases except one severe case where blood transfusion was needed and anticoagulant treatment was stopped for 7 days. The bleeding risk was significantly higher for the surgical procedures of the nose than those in other areas (21% versus 6%, P = 0.014), but was not influenced by the international normalized ratio (INR) of blood coagulation, size, site and type of the lesion, surgical procedure, and sex and age of the patients. The bleeding rate in patients not on any anticoagulation therapy was significantly lower (6/211 = 3%). Across both groups, just over 80% of the bleeding episodes were within the first two days (55% on the same day and 32% on the next day) of the surgery. No bleeding was recorded after 5 days. Our data suggest that cutaneous surgery in the head and neck region can be safely performed with continued phenprocoumon therapy in most cases in an INR range of 1.3-3.4, but rarely severe bleeding does occur and can be managed with a close-contact follow-up and with 24-h on call services during the first two days postoperatively., (Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: Gene products, which show a significant association to cell proliferation and cell cycle control, are of high scientific interest, because genes as well as gene products could be possible targets for a specific therapeutic approach and eventually be prognostic markers., Materials and Methods: Cyclin D1 expression and amplification as well as the Ki-67 expression status were examined in a two tissue microarray analysis for head and neck squamous cell carcinoma (HNSCC) including 546 patients. A tumour site-specific analysis and a survival analysis of 222 oral squamous cell carcinoma (OSCC) patients were performed. Cyclin D1 amplification status was examined with fluorescence in situ hybridisation analysis, while cyclin D1 expression and Ki-67 expression status were examined with IHC., Results: Amplification of the CCND1 gene and immunohistochemical expression of cyclin D1 and Ki-67 were examined in 546 tumours of the head and neck region in two tissue microarrays. CCND1 amplification was significantly more frequent in pharyngeal carcinomas (63%) than in laryngeal (37%) and oral (25%) carcinomas. Among the 222 cases of OSCCs, both CCND1 amplification and cyclin D1 expression were significantly associated with overall survival of the patients (p = 0.0127 and p = 0.0004, respectively). Ki-67 expression was significantly associated with cyclin D1 expression and with amplification of the CCND1 gene (p = 0.0002 and p = 0.0015, respectively) but not with patient overall survival., Conclusion: Our results suggest the prognostic value of CCND1 amplification and cyclin D1 expression for patients with OSCC and highlight the genetic differences in HNSCC of different subanatomic localisation., Clinical Relevance: Cyclin D1 expression and CCND1 amplification seem to have a prognostic value for OSCC. Further studies of HNSCC should always consider subanatomic genetic differences.

Objectives: The present study aims to investigate the relevance of immunohistochemical p53 expression in carcinomas of the oral cavity and of the head and neck region. Long-term clinical and histopathological follow-up findings as well as HPV status are correlated with the results of this examination., Materials and Methods: Sections made from two tissue arrays composed of 222 oral squamous cell carcinomas and 427 squamous cell carcinomas of the head and neck region, respectively, were examined for p53 expression and Ki-67 index by means of immunohistochemistry. Correlation of long-term clinical findings of the patients and pathological features of tumours with laboratory results were examined statistically., Results: No significant correlation was found between the p53 immunohistochemical expression in the 207 oral carcinomas and features of the tumours and patient outcomes. There was no significant association between the Ki-67 labelling index and the p53 expression., Discussion: Our failure in detecting any association of the p53 immunohistochemical expression regardless of HPV status with clinical features of these tumours suggests it lacks a prognostic value for squamous cell carcinomas of the oral cavity., Clinical Relevance: The prognostic value of p53 immunostaining in oral squamous carcinoma is not clarified yet. In the present study, there is no impact on any prognostical item nor even a correlation with cell proliferation (Ki-67) regardless of HPV status.

Background: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) was found overexpressed in various cancer types suggesting its possible role in carcinogenesis. Analysis of IMP3 expression in head and neck squamous cell carcinomas (HNSCC) is rare so that we evaluated it using tissue microarray method., Method: Immunohistochemical analysis of IMP3 was performed on samples from over 400 patients. The expression was measured semiquantitative, subsequently divided into four categories (negative, weak, medium, or strong) and correlated with several available clinicopathologic parameters., Results: For HNSCC, positive IMP3 expression was observed in patients with all tumor stages (pT1-4) and nodal stages (pN0-3), showing also significant statistical correlation (P=0.023 and P=0.0013, respectively). No further correlations were found. Separate analysis according to tumor localization (oral cavity, oropharyngeal, and laryngeal) showed a significant correlation of positive IMP3 expression and overall survival (P=0.038) only in patients with tumors of the oral cavity. Multivariate analysis showed IMP3 as an independent predictive marker for oral squamous cell carcinomas (OSCC)., Conclusion: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression might be used as an independent prognostic factor in the subgroup of OSCC., (© 2012 John Wiley & Sons A/S.)

This study analyzed the surgical outcome and complications of 1000 microvascular free flaps performed at the authors' institution in Germany, between 1987 and 2010. 972 patients underwent reconstruction with 1000 flaps: 28% latissimus dorsi flaps, 27% radial forearm flaps, 20% iliac crest flaps, 12% fibula flaps, 6% jejunal flaps, 2% anterolateral thigh flaps, and 5% other flaps. 130 failures (7.6%) were encountered, including 58 complete flap failures (44.6%) and 72 partial free-flap failures (55.4%). This study confirms that free flaps are extremely reliable in achieving successful reconstruction of the head and neck, but it is essential that complications be recognized and addressed early in their course to prevent or minimize devastating consequences. Owing to the large number of possible errors in flap transplantation, microsurgeons should always check everything for themselves. The on-duty doctors and nursing staff should not be trusted blindly. Venous thrombosis and cervical haematoma are the most common complications at the recipient site and are mainly responsible for flap failure, while complications occurring at the donor site may result from dehiscence and graft necrosis. When a compromised flap is identified, surgical re-exploration should not be deferred., (Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: This retrospective study was intended to determine the incidence and causes of postoperative complications in patients following head and neck reconstruction using microvascular free flaps., Patients and Methods: A total of 202 consecutive microvascular free flaps were performed for reconstruction of the head and neck by the same surgeon, 85% of the defects arose following the treatment of malignancies. Flap donor sites included latissimus-dorsi flap (n=83), radial forearm (n=35), fibula (n=31), iliac crest (n=36), TRAM flap (n=3), groin flap (n=l), jejunal flap (n=13). The incidence of postoperative complications and patient-related characteristics (age, sex, diagnosis, comorbidity level, operation duration, defect site, history of radiotherapy/chemotherapy) were retrospectively analyzed., Results: Free flaps proved to be extremely reliable, with a 2.9% incidence of free flap failure. Postoperative medical complications occurred in 11.4% of cases, with cardiac, pulmonary and infectious complications predominating., Conclusion: The present study confirms that free flaps are extremely reliable in achieving successful reconstruction of the head and neck. The incidence of postoperative complications is related to the preoperative comorbidity.

The aim of this study was to retrospectively analyze surgical outcome and complications of 540 free flap procedures performed at the Department of Oral and Maxillofacial Surgery of the University Medical Center Hamburg-Eppendorf during 1987-2005. A total of 532 patients were reconstructed with 540 flaps: 32% were latissimus dorsi flaps, 23% were radial forearm flaps, 21% were iliac crest flaps, 10% were fibula flaps, 6% were jejunal flaps, and 8% were other flaps. Thrombosis of one of the vessels and hematoma were the most frequent causes of failure in microvascular free tissue transfer. A total free flap failure occurred in 34 (6.2%) and a partial flap failure in 42 (7.7%) patients. The most reliable flap in regard to survival was the radial forearm flap. The present study confirms that free flaps are extremely reliable in achieving successful reconstruction of the head and neck.