The myofiber disarray in the inner myometrium, and the nuclear membrane irregularities in adenomyosis, are evidence for ultramicro-trauma in adenomyosis. The migrating nonleukocytic pale cells may be involved in pathogenesis of adenomyosis.

Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis

Persistent infections by high-risk human papillomaviruses (HPVs) are the main etiological factor for cervical cancer, and expression of HPV E7 oncoproteins was suggested to be a potential marker for tumor progression. The objective of this study was to generate new reagents for the detection of the HPV18 E7 oncoprotein in cervical smears. Rabbit monoclonal antibodies against recombinant E7 protein of HPV type 18 (HPV18) were generated and characterized using Western blotting, epitope mapping, indirect immunofluorescence, and immunohistochemistry. One clone specifically recognizing HPV18 E7 was used for the development of a sandwich enzyme-linked immunosorbent assay (ELISA). The assay was validated using recombinant E7 proteins of various HPV types and lysates from E7-positive cervical carcinoma cells. A total of 14 HPV18 DNA-positive cervical swab specimens and 24 HPV DNA-negative-control specimens were used for the determination of E7 protein levels by the newly established sandwich ELISA. On the basis of the average absorbance values obtained from all 24 negative controls, a cutoff above which a clinical sample can be judged E7 positive was established. Significant E7 signals 6-to 30-fold over background were found in 7 out of 14 abnormal HPV18 DNA-positive cervical smear specimens. This feasibility study demonstrates for the first time that HPV18 E7 oncoprotein can be detected in cervical smears. P ersistent infections by human papillomaviruses (HPVs) are the main etiologic factor for cervical cancer (41). Approximately 85% of cervical cancers are squamous cell carcinomas (SCCs) which arise from dividing keratinocytes in the squamous epithelium of the ectocervix and 15% are adenocarcinomas (ACs) which arise from glandular cells located in the endocervix (3, 25). About 40 HPV genotypes that can infect epithelial squamous and glandular cells in the cervical mucosa have been described. On the basis of epidemiological and biochemical data, only a subgroup of HPV types, referred to as high-risk HPVs, is associated with intraepithelial lesions that have a high potential for progression to invasive carcinoma. Infections by high-risk HPV genotypes have been detected in virtually all cervical cancers (37). At least 15 highrisk HPV types have been associated with these cancers. HPV type 16 (HPV16) and HPV18 are the most prevalent genotypes worldwide in SCCs as well as in ACs (23).A persistent infection with oncogenic HPVs is necessary for the development of cervical precancer and cancer (3, 37, 40, 41). Initial events of cervical carcinogenesis after viral infection by highrisk HPV types are specific changes that overcome the transcriptional control of viral gene expression in the infected keratinocytes (40). Inactivation of these cellular control functions permits deregulated transcription of the early viral genes E6 and E7. This event triggers reprogramming of cell proliferation, apoptosis, differentiation, metabolism, epigenetic reorganization, and genomic instability (21). These changes can support the integration ...

A 19-yr-old woman with previously diagnosed clear cell adenocarcinoma was referred to the Charité for further treatment. Biopsies were taken from the cervix, the endometrium, pseudomembranes in the peritoneum, and sentinel lymph nodes. The morphologic picture of pseudomembranes and inflammation together with the provided information about plasminogen deficiency of the patients led to the hypothesis of ligneous cervicitis. The previously taken biopsies of the adenocarcinoma were reevaluated and showed a clear cell lesion. Further immunohistochemical examination with antibodies against p16, Ki67, CEA, and p53 could not prove its malignant character. As a result we diagnosed an atypical form of microglandular hyperplasia in a patient with ligneous cervicitis. Ligneous cervicitis is a rare inflammatory condition that might affect all mucus membranes in patients with plasminogen deficiency. This case shows the importance of correlating pathologic and clinical findings in the diagnosis of ligneous cervicitis because of the rarity of the disease and the heterogeneity at presentation.