Stefan Gottschlich

Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in patients with head‐and‐neck squamous‐cell carcinoma

Human papillomaviruses (HPVs) have been recognized as an essential pathogenic factor in anogenital cancer. HPV DNA has also been found in a subgroup of head‐and‐neck squamous‐cell carcinomas (HNSCCs), and a causative role of the virus in the development of these tumors has been suggested by the concomitant inactivation of the tumor‐suppressor protein pRb. Using 4 second‐generation ELISAs, we found antibodies against at least 1 of the oncoproteins E6 and E7 of the high‐risk HPV types 16 and 18 in 11 of 92 sera (12%) taken from HNSCC patients at or near diagnosis, in 1 of 52 sera (2%) taken from HNSCC patients >6 months after diagnosis and in 10 of 288 sera (3.5%) taken from sex‐ and age‐matched healthy control individuals of the normal population. In 11 of the 12 seropositive HNSCC cases, antibodies were directed against HPV16 proteins. In patients, the HPV16 antibodies were mostly of high titer, and in 6 cases, antibodies against both HPV16 oncoproteins were present. Seven of the 8 HPV16 antibody–positive sera from the control group were of low titer, and none of the 10 antibody‐positive sera reacted with both oncoproteins of the same HPV type. The HPV type of the antigens detected by the antibodies in HNSCC patients correlated well with that of the HPV DNA found in the tumor. Of 19 patients known to have HPV16 DNA–positive tumors, 7 (37%) also had HPV16 E6 and/or E7 antibodies. Our finding suggests that the antibodies were formed in an immune response against HPV E6 and E7 proteins expressed in the HNSCC and thus strongly supports the concept of a biologically active role of HPV in the development of a subgroup of HNSCC. Int. J. Cancer 85:815–818, 2000.

Ultrasound-guided interstitial Nd:YAG laser treatment of voluminous hemangiomas and vascular malformations in 92 patients

In many cases voluminous vascular anomalies of the head and neck region are still treated with conventional surgery, although neodymium:yttrium‐aluminum‐garnet (Nd:YAG) laser therapy offers a valuable treatment alternative. Ninety‐two patients with voluminous hemangiomas and vascular malformations were treated with interstitial Nd:YAG laser therapy (power density, 1300 to 3300 W/cm2), partly complemented by a noncontact‐mode Nd:YAG laser light application (energy density, 1000 to 2500 J/cm2). The vascular tumors had a diameter of more than 3 cm in at least two dimensions. Treatment was carried out under ultrasound and manual control. Nearly 60% of the patients (n = 55) showed a complete clinical regression. Thirty‐three patients (35.8%) had a partial regression and were satisfied with the treatment outcome. Four patients were treated unsuccessfully with the laser, and three of them subsequently underwent conventional surgery. Only nine of the 92 patients (9.8%) showed cosmetic or functional impairments. The results of this first consecutive series study with a retrospective clinical evaluation of the interstitial Nd:YAG laser therapy of voluminous hemangiomas and vascular malformations in a large patient group demonstrate a high effectiveness of this novel therapy modality.

Metalloproteinases and their inhibitors: influence on tumor invasiveness and metastasis formation in head and neck squamous cell carcinomas.

Matrix metalloproteinases (MMPs) play an important role in tumor invasiveness. This study investigates the expression status of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in head and neck squamous cell carcinomas (HNSCC).

Selective upregulation and amplification of the lysyl oxidase like‐4 (LOXL4) gene in head and neck squamous cell carcinoma

Members of the lysyl oxidase family (LOX) are copper and lysyl‐tyrosine quinone cofactor‐containing amine oxidases that are important for the assembly and maintenance of components of the extracellular matrix. Our previous results demonstrated that a novel member, LOXL4, is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. Results of the current study showed overexpression of the LOXL4 transcript in 74% (46 of 62) of invasive HNSCC tumours and 90% of both primary and metastatic HNSCC cell lines. Significant correlation was found between LOXL4 expression and local lymph node metastases versus primary tumour types (p < 0.01) and higher tumour stages (p < 0.01). Immunocytochemistry demonstrated cellular overexpression of the LOXL4 protein that correlated with the increased mRNA transcription in HNSCC cells. HNSCC cell lines displayed in significant subset of nuclei increased copies of the LOX4 gene locus on chromosome 10q24, demonstrated by fluorescence in situ hybridization (FISH). Extensive metaphase cytogenetic analysis was performed on UTSCC19A cells, identifying an isochromosome i(10)(q10). Taken together, these results highlight LOXL4 expression as a distinctive trait and suggest a functional role for LOXL4 in the molecular pathogenesis of invasive head and neck carcinomas. Copyright

Human papillomaviruses in lymph node neck metastases of head and neck cancers.

Conclusion The results of this study corroborate earlier findings that human papillomavirus (HPV)16 is the most prevalent type of HPV in squamous cell carcinomas of the head and neck (SCCHNs) and reinforce a possible influence of HPV on SCCHN progression by showing that the majority of HPV-positive patients harbor HPV16 (or HPV33) both in their primary tumors and in lymph node neck metastases (LNNMs). Objective HPVs are causally associated with carcinomas of the uterine cervix and have also been linked to a subset of SCCHNs. In order to further investigate the predicted causative role of HPV in SCCHNs, we analyzed pairs of primary tumors and LNNMs or LNNMs alone for the presence of HPV DNA using polymerase chain reaction (PCR). Material and methods DNA was extracted from fresh frozen tissue samples of primary tumors and the corresponding LNNMs of 18 patients and from LNNMs alone in 17 patients. For the detection and typing of HPV, PCR was performed using both type-specific and consensus primer pairs, followed by Southern hybridization and, in selected cases, sequencing of the PCR products. Results Of the 35 patients investigated, 22 (63%) were found to have HPV DNA in their tumors: HPV16 DNA in 21 cases and HPV33 in 1. The highest HPV prevalence was detected in tumors of Waldeyers tonsillar ring (8/9 patients; 89%). Of the 18 patients in whom primary tumors and LNNMs were analyzed, 7 (39%) were HPV-positive in both samples (HPV16, n=6; HPV33, n=1), in 3 (17%) the primary tumors were HPV-negative and the LNNMs HPV16-positive and in 1 (5.5%) the primary tumor contained HPV16 and the LNNM was negative. Interestingly, of the 7 patients in whom LNNMs had been detected only several months after diagnosis and treatment of the primary tumors, only 1 showed infection with HPV (HPV33).

p53 serum antibodies as prognostic indicator in head and neck cancer

Abstract p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The post-therapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer.

Experimental and clinical results of Er:YAG laser stapedotomy

At the beginning of the 1980s, different laser types were used for stapes surgery to reduce potential harm to inner ear structures through manipulation with conventional instruments during stapedotomy. Most clinical studies were carried out with the CO2 or the argon laser. The Er:YAG laser has been used rarely in patients with otosclerosis.

Human proteinase 3 (PR3) and its binding molecules: implications for inflammatory and PR3-related autoimmune responses.

Abstract:  Human proteinase 3 (PR3) is a multifunctional serine protease, mainly located in the azurophilic granules and on the cell surface of polymorphonuclear leukocytes (PMN). Cumulated data indicate that PR3, which is the main target autoantigen of antineutrophilic cytoplasmic antibodies (ANCA), interacts with several surface receptors and participates in the local inflammatory response. Herein, we summarize the efforts made to elucidate ANCA‐binding epitopes of PR3, extended by data derived from the use of a random peptide library. The inserts for 107 peptides were obtained by panning of a random peptide library with PR3‐ANCA+ immunoglobulins. Analysis of the amino acid sequences of the inserted peptides derived from isolated positive clones suggested that they do not belong to linear epitopes of PR03 and possess a high proportion of positively charged amino acids. Furthermore, this article focuses on immune functions of PR3 with respect to PR3 modulation of cell activation via cleavage of protease‐activated receptor‐2 (PAR‐2) and as binding protein for the proinflammatory cytokine IL‐32α. Altogether, there are a number of (auto)molecules that bind to PR3, some of them even competitive and each binding interaction seems to have specific implications.

Tracing Human Papillomavirus DNA in Nasal Polyps by Polymerase Chain Reaction

Human papillomavirus (HPV) infections are related to the genesis of various benign and malignant human neoplasias. The HPV types 16 and 18 seem to be causally related to the development of most squamous cell carcinoma of the anogenital tract and a proportion of carcinomas of the upper aerodigestive tract. The near 100% positivity of the HPV types 6 and 11 in laryngeal papillomatosis is well established. We investigated whether HPV also plays a role in non-neoplastic mucosal entities such as sinunasal polyposis, the genesis of which has been discussed as being triggered by viral infections. On DNA from 39 sinunasal polyps (33 patients), polymerase chain reaction (PCR) was performed using

Microendoscopic treatment of the hypopharyngeal diverticulum with the CO2 laser.

The hypopharyngeal (Zenkers) diverticulum is a herniation of mucosa and submucosa on the posterior wall of the pharynx. The only treatment is surgical.