Human papillomavirus genotype distribution in cytologically screened women from northwest Germany.

INTRODUCTION: In this study, we evaluate the distribution of 24 human papillomavirus (HPV) genotypes in a cohort of 3,381 cytologically screened women from a rural area of northwest Germany, in correlation to cytological diagnoses and histological outcomes. MATERIALS AND METHODS: We present a retrospective study in which the HPV-genotyping results of women who attended the German cervical screening program were correlated to cytological diagnosis and histological outcome. RESULTS: HPV genotyping showed marked differences among cervical lesions. Although HPV-51 was common in all cervical lesions, it was rarely detected as single-type HPV infection in high-grade cervical intraepithelial neoplasia (CIN)3 (2/118 cases). HPV-16 and 18 were more common in CIN3 (57.6%) than in CIN2 (21.8%), but they were absent in 42.4% of all CIN3 lesions in our cohort. DISCUSSION: Our data show that HPV-16, HPV-31, HPV-51, HPV-53 and HPV-42 are the most prevalent HPV types in the different cervical lesions in this region of northwest Germany. HPV genotyping has been shown to be a powerful tool to triage atypical squamous cells of undetermined significance lesions. Considering the observed heterogeneity of HPV types in CIN2, it could also be useful to triage CIN2+ lesions. Our results underline the usefulness of a morphologically controlled screening program with HPV genotyping as a powerful additional tool.

Quantitative measurement of telomerase activity and localization of its catalytic subunit (hTERT) in chronic inflammation of capsule formation around various model implants and in sarcomas in a rat model.

Telomerase is upregulated in some preneoplastic lesions and overexpressed in the majority of malignant tumors, but absent in most nonneoplastic somatic tissues. We analyzed telomerase activity using TRAP-assay in capsule tissues in a rat model with chronic inflammation and in tumor, and visualized the catalytic subunit of telomerase (hTERT) by immunhistochemistry. Significant elevated telomerase activity was found in tumor tissue compared with nonneoplastic tissue (p = 0.047). Cases with a strong inflammation in capsule tissue showed a specific telomerase activity. In these cases, there were no significant differences in telomerase activities compared with malignant tumor tissue. We demonstrate elevated telomerase activity and its diagnostic limits around model implants in a rat model, and visualize its expression not only in malignant tissue but also in inflammatory cells. So the quantitative measurement of telomerase activity should not be applied in general as a marker for malignancy in capsule tissue.

Implementation of a map in radical prostatectomy specimen allows visual estimation of tumor volume.

INTRODUCTION: Tumor volume is one of the best documented prognostic factors for prostate cancer. There are several methods to gain this important parameter but unfortunately most of the clinicians in the world do not get this information in their routine practice from the pathologist. We developed a standardized method to handle radical prostatectomy specimens including a special form of mapping in order to document relevant morphological data. The aim of this study was to investigate if our model of mapping prostate cancer, which we use in routine practice, may serve for visual estimation of tumor volume. METHODS: We estimated the tumor volume of prostate cancer by visual estimation of 350 maps of radical prostatectomy specimens and correlated these data with established prognostic parameters and clinical outcome. RESULTS: Significant correlations between tumor volumes, as obtained from our mapping, and known prognostic parameters such as preoperative serum levels of prostatic specific antigen, loss of differentiation, histological grade, lymph node metastasis, and margins were found. In a multivariate analysis, only Gleason score and tumor stage were shown to be independent prognostic parameters. DISCUSSION: We demonstrate that mapping of prostate cancer is more than a simple method of documentation but may serve as a method for visual estimation of tumor volume of prostate cancer after radical prostatectomy. This method can further be used for a visual documentation of the tumor stage independent of changes in the TNM classification. The method is inexpensive and practicable and can therefore be applied in routine surgical pathology.

Mucinous cystadenocarcinoma--an extremely rare tumor in a young patient.

We report on an extremely rare case of pulmonary mucinous cystadenocarcinoma. A 29-year-old male patient was admitted because of progressive enlargement of a right lower lobe mass over a period of 10 years. Right lower lobectomy was performed after a malignant mucinous cystadenocarcinoma was diagnosed by intraoperative frozen section. PET and CT scans did not detect metastatic disease. This case is the youngest patient reported so far with a malignant pulmonary mucinous cystadenocarcinoma and highlights the importance of close follow-up of indeterminate pulmonary nodules in patients with unremarkable history.

Radiation-induced capsule tissue reactions around textured breast implants in a rat model.

Capsule fibrosis and other complications around various filled breast implants were evaluated in a rat radiation model after 12 months of implantation. Model implants, one per rat, were implanted subcutaneously. One month after subcutaneous implantation, high voltage radiation followed one half each group. A higher rate of capsule fibrosis occurred in radiated animals. Malignant tumors at the implantation site developed in 40% of radiated and 24% of non-radiated animals, with a much higher rate of mitosis in the radiated group (Mann-Whitney, P=0.008). The presence of an implant is a cofactor for tumor development in rats (chi2-test, chi2=6.927; P=0.008) as well as radiation, since none of the control animals developed tumors. Applied to humans, capsule contracture (fibrosis) is a common complication of radiation, while development of radiation-induced sarcoma is a rare complication after postoperative radiotherapy by all account. Still further long-term follow-up human studies are necessary.

[Cyclooxygenase-2-expression in bladder cancer: tumor-biological and clinical implications]. / Cyclooxygenase-2-Expression beim Harnblasenkarzinom: Tumorbiologische und klinische Bedeutung.

PURPOSE: Cyclooxygenase-2 (Cox-2) contributes to the carcinogenesis of human tumors by various mechanisms. As Cox-2-expression has been found in most human neoplasms, selective Cox-2-inhibitors could be used as a molecular targeted therapy, and first clinical trials have already been initiated. Moreover, Cox-2-inhibitors have been shown to add to the activity of conventional cytotoxic therapies in experimental and clinical studies. We analyzed Cox-2-expression in bladder cancer and its implications on clinical parameters. MATERIALS AND METHODS: Cox-2-expression was evaluated immunohistochemically in 157 patients undergoing radical cystectomy. Sixty-two patients had received cisplatin-based treatment during follow-up, either as adjuvant therapy or for metastatic disease. Cox-2-expression was correlated with clinical and pathological parameters, survival data and outcome of chemotherapy. RESULTS: Cox-2 was expressed in 83.4 % of tumors. No association was found with TNM-staging and histological grading, but a significant relation to the histologic subtype (transitional vs. squamous cell carcinoma, p = 0.038) was present. Survival analysis showed no impact of Cox-2-expression on overall or disease-free survival. However, a subgroup of chemotherapy patients demonstrated a significant correlation of strong Cox-2-expression with worse overall survival time (p = 0.01). CONCLUSIONS: Cox-2-expression was found in the majority of invasive bladder tumors. For patients who underwent chemotherapy, a significant relation of Cox-2-expression and worse overall survival was demonstrated. Cox-2 seems to be an interesting molecular target for the diagnosis and therapy of bladder cancer. Further experimental and clinical studies are warranted to elucidate whether Cox-2-inhibition can serve as an additive therapy to chemotherapy of bladder cancer.

Frequent detection and immunophenotyping of prostate-derived cell clusters in the peripheral blood of prostate cancer patients.

BACKGROUND: Recent scientific studies have failed to determine parameters for the assessment of prostate cancer aggressiveness. The present study deals with the detection of blood-borne cancer cells based on polymerase chain reaction (PCR) and cell enrichment methods. The contradictory results reported in the literature have called into question the clinical usefulness of this diagnostic method in the preoperative staging of clinically localized prostate cancer. METHODS: We established a combined method of density gradient centrifugation and immunomagnetic separation using epithelium-specific antibodies, i.e. cytokeratins, to isolate prostate-derived circulating cells from the peripheral blood of patients with prostate cancer. Isolated cells were characterized by DNA staining and immunocytochemistry using antibodies for the detection of prostate-specific antigen (PSA), proliferation-associated proteins (MIB-1, H1 and H3) and apoptosis-associated proteins (M30, c-FasR). RESULTS: We applied these methods to 68 prostate cancer patients and were able to isolate cell clusters in 98%. Immunophenotypic and morphological characterization of PSA-positive prostate-derived cell clusters found in the peripheral blood of prostate cancer patients showed two main populations: 1) in 35% of the investigated prostate cancer patients we detected rounded cell aggregates of probable cancer cells expressing proliferation-associated proteins and lacking apoptosis-associated protein expression; 2) in all cases there was a high frequency of circulating dysmorphic cell clusters positive for apoptosis-associated protein expression. CONCLUSION: Our results demonstrate the existence of at least two different types of blood-borne prostate-derived circulating cell clusters. Of these, only the less frequent, round, small cell clusters harbor features that are probably necessary for the cells to survive for metastatic spread.

Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy?

An escalation in the incidence of oral cancer and its attributable mortality has been observed in recent decades in Europe; oral cancer is expected to become a public health problem in the foreseeable future. However, survival rates have remained at a disappointingly stable level despite significant development in the multimodality treatment of the disease. Additionally, due to the limited prognostic value of conventional prognostic factors and the uniformity of treatment strategies, several patients are still over- or under-treated with significant personal and socio-economical impact. Here we review some promising prognostic and predictive markers that can help the clinician to improve prognostic accuracy and define the most appropriate management for the individual patient with oral cancer.

[Congenital prepubic sinus: etiology and therapy]. / Kongenitaler präpubischer Sinus: Atiologie und Therapie.

INTRODUCTION: Congenital prepubic sinus (CPS) is a rare diagnosis. It is defined as a blind-ending tract originating from the midline of the genital region. There are three types of CPS classified according to the course of the tract and location of the skin opening. The etiology is thought to be an intussusception during fusion of the abdominal wall or, alternatively, incomplete urethral duplication. CASE REPORT: We report on a two-year-old boy with a skin fistula on the dorsal side of the penis. A slight secretion occurred when the surrounding subcutaneous tissue was compressed. After total resection of the sinus, histological examination revealed that the tract was lined primarily with multilayered epithelium. Immunohistochemical studies showed that the sinus was lined with transitional and squamous epithelium. At the base the lining epithelium was transitional and shifted distally to noncornifying squamous epithelium. The epithelial layer therefore corresponded to the inner surface of the urethra, thus supporting the assumption that CPS results from incomplete urethral duplication. CONCLUSION: The immunohistochemical examination of the epithelium of Type II CPS proved, in this case, the existence of urothelium as the inner surface of the sinus. In view of this evidence it appears likely that the congenital prepubic sinus can be classified etiologically as an incomplete urethral duplication.

Influence of local complications on capsule formation around model implants in a rat model.

We studied the capsule formation around various filled breast implants and other related changes in distant organs (e.g., liver, spleen, lymph nodes) in a rat model 3 and 6 months after implantation. Model implants, one per rat, (filled with saline, n = 19; silicone, n = 14; cohesive silicone, n = 17; and hydrogel, n = 19) were implanted subcutaneous in the lower back of rats. The animals were sacrificed regularly after 3 and 6 months of implantation or when wound defects occurred. The capsules and organs were examined histologically, and immunohistology of the capsules was performed. A monoclonal antibody specific for AIF-1 (allograft inflammatory factor 1) was used to detect activated macrophages. Wound defects occurred most frequently after implantation of saline and hydrogel implants. Increased capsule thickness was associated with increased grade of inflammation, fibrosis, and the type of implant filling. There was a significant positive correlation between capsule thickness, presence of chronic inflammation, and AIF-1-positive macrophages (p < 0.0001), indicating that inflammation plays an important role in capsule formation. Remarkably, saline and silicone implants (in absence of local complications) cause only a blande slight fibrosis in capsules after 6 months of implantation, whereas capsules around cohesive silicone implants exhibited a more severe fibrosis with an increased capsule thickness. Most importantly, hydrogel seems to be most potent to induce an inflammatory infiltrate with AIF-1 expressing macrophages at the implantation site, independent of implantation time, and capsules also produced a significant increase in thickness after 6 months.

Prognostic relevance of Ki-67 antigen expression in 329 cases of oral squamous cell carcinoma.

Prognostic relevance of Ki-67 staining in oral squamous cell carcinomas was investigated by immunohistochemical expression in 329 cases of squamous cell carcinoma of the oral cavity due to a formamide pretreatment. The growth fraction (Ki-67 labelling index, LI) was correlated to histopathological grading, lymphocytic reaction, stroma/tumour proportion, pattern of invasion, mitotic rate, degree of keratinisation, tumour size, thickness of tumor, depth of invasion, lymph node involvement and five-year survival rate. Highly significant inverse correlation was found between the Ki-67 LI, the stroma/tumour proportion and the degree of keratinisation whereas no correlation could be established between the Ki-67 LI and all the other histological and clinical paramters. Ki-67 staining alone has no prognostic relevance in oral cancer.