Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) is a causal factor in virtually all cervical and a subset of oropharyngeal squamous cell carcinoma (OP-SCC), whereas its role in laryngeal squamous cell carcinoma (L-SCC) is unclear. METHODS: Formalin-fixed paraffin-embedded (N=154) and deep-frozen tissues (N=55) of 102 L-SCC patients were analysed for the presence of 51 mucosal HPV types. HPV DNA-positive (HPV DNA+) cases were analysed for E6*I mRNA transcripts of all high risk (HR)/probably/possibly (p)HR-HPV identified, and for HPV type 16 (HPV16) viral load. Expression of p16(INK4a), pRb, cyclin D1 and p53 was analysed by immunohistochemistry. RESULTS: Ninety-two patients were valid in DNA analysis, of which 32 (35%) had at least one HPV DNA+ sample. Among the 29 single infections, 22 (76%) were HPV16, 2 (7%) HPV56 and 1 each (4%) HPV45, HPV53, HPV70, HPV11 and HPV42. Three cases harboured HPV16 with HPV33 (twice) or HPV45. Only 32% of HPV DNA+ findings were reproducible. Among HPV16 DNA+ L-SCC, 2 out of 23 (9%) had high viral loads, 5 out of 25 (21%) expressed E6*I mRNA and 3 out of 21 (14%) showed high p16(INK4a) and low pRb expression (all three HPV16 RNA-positive), immunohistochemical marker combination not identified in any other HPV DNA+ or HPV DNA-negative (HPV DNA-) L-SCC, respectively. CONCLUSION: HPV type 16 has a causative role in a small subgroup of L-SCC (<5% in this German hospital series).

Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma.

Aberrant promoter methylation of different DNA repair genes has a critical role in the development and progression of various cancer types, including head and neck squamous cell carcinomas (HNSCCs). A systematic analysis of known human repair genes for promoter methylation is however missing. We generated quantitative promoter methylation profiles in single CpG units of 160 human DNA repair genes in a set of DNAs isolated from fresh frozen HNSCC and normal tissues using MassARRAY technology. Ninety-eight percent of these genes contained CpG islands (CGIs) in their promoter region; thus, DNA methylation is a potential regulatory mechanism. Methylation data were obtained for 145 genes, from which 15 genes exhibited more than a 20% difference in methylation levels between tumor and normal tissues, manifested either as hypermethylation or as hypomethylation. Analyses of promoter methylation with mRNA expression identified the DNA glycosylase NEIL1 (nei endonuclease VIII-like 1) as the most prominent candidate gene. NEIL1 promoter hypermethylation was confirmed in additional fresh frozen HNSCC samples, normal mucosa, HNSCC cell lines and primary human skin keratinocytes. The investigation of laser-microdissected tissues further substantiated increased methylation levels in tumor versus matched non-tumor cells. Immunohistological analysis revealed significantly less NEIL1 protein expression in tumor tissues. 5-Aza-2'-deoxycytidine treatment and DNMT1 knockdown resulted in the re-expression of NEIL1 in HNSCC cell lines, which initially carried hypermethylated promoter regions. In conclusion, our results suggest that DNA methylation contributes to the downregulation of NEIL1 expression and might thus have a role in modulating the response to therapies of HNSCC.

A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel.

Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then monthly follow-up; open-label dosing began as needed after three blinded treatments. Tumour response was defined as complete (100% regression) or partial (50-99% regression) sustained for > or =28 day, and patient benefit as attainment of palliative or preventive goals prospectively selected by investigators and patients. With cisplatin/epinephrine gel, 25% (14 out of 57) of tumours responded (16% complete regression, 9% partial regression), vs 3% (one out of 35, complete regression) with placebo (P=0.007). Patient benefit was positively associated with target tumour response in the blinded period among cisplatin/epinephrine gel recipients (P=0.024): 43% (six out of 14) of responders benefited, vs 12% (five out of 43) of non-responders. The most frequent adverse event was pain during injection and the next most frequent was local cytotoxic effects consistent with the gel's mode of action. Systemic adverse events typical of intravenous cisplatin were uncommon. Intratumoural therapy with cisplatin/epinephrine gel provided safe, well-tolerated, effective palliative treatment for patients with locally advanced head and neck squamous cell carcinoma, who lack other satisfactory treatment options.

[Carcinoid of the middle ear. Further therapy after primary tumor excision?]. / Karzinoid des Mittelohrs. Weitere Therapie nach primärer Tumorexstirpation?

The carcinoid tumor of the middle ear is a very rare neoplasm which in general is regarded as benign but may be mistaken for an adenocarcinoma because of its histological heterogeneity. Typical, however, is its neuroendocrine and mucinous differentiation so that an unequivocal diagnosis is possible by means of immunohistochemistry and electron microscopy. As the tumor is very rare, there is no statistical evidence as to whether further treatment is necessary after primary exstirpation of the tumor. Therefore, a review of the literature was performed. We report about a 28-year-old male patient with a carcinoid tumor of the left tympanic cavity. Without any further treatment there has been no evidence for either recurrence or metastases 32 months after surgical resection. As treatment of choice we recommend conservative surgery with complete removal of the tumor and a clinical follow-up on a regular basis.

[Antimycotic therapy in otomycosis with tympanic membrane perforation]. / Antimykotische Therapie bei Otomykose mit Trommelfelldefekt.

Especially after prolonged antibiotic ototopic therapy otomycosis is not rare. An inoculation of fungi into the tympanic cavity however may have serious sequelae. Therefore an eradication of fungi from the external auditory canal is imperative before surgery. In addition to thorough cleaning of the outer ear canal antimycotic preparations are recommended in treating otomycosis. However, all of the commercially available ear drops contain ototoxic agents. In the case of defects of the tympanic membrane a damage of the inner ear may result. Alternatively, we suggest an aqueous solution of Miconazol 0,5%.

Carcinoid tumor of the middle ear in a 28-year-old patient.

Carcinoid tumor of the middle ear is an extremely rare condition. The origin of the tumor cells is still speculative and the closeness of relationship to adenomas of the middle ear has been a matter of discussion since the first description of this tumor entity in 1980. In this study we report a case of a 28-year-old male patient with a carcinoid tumor of the middle ear. We present the results of histomorphological, immunohistochemical and electron microscopic examinations and compare our findings to those of previously published cases.

[Comparative studies on collagen expression of chondrocytes in monolayer and spheroid culture]. / Vergleichende Untersuchungen über die Kollagenexpression von Chondrozyten in Monolayer- und Sphäroidkultur.

Dedifferentiation of cells is well known in cell culture biology. This phenomenon is examined in comparative studies on collagen expression of chondrocytes in monolayer and spheroid culture. Immunohistochemical studies were carried out by the indirect peroxidase technique. In the differentiated state a positive reaction for collagen type II was found. This was lost as dedifferentiation took place, in which case positivity for collagen types I, III, and V increased.