[Risk-adapted multimodal laboratory cervical screening---Pap test of the future?]. / Risikoadaptierte multimodale gynäkozytologische Krebsvorsorge. Pap-Test der Zukunft?

The objective of screening for cervical cancer is to reduce mortality and incidence of the disease. To date there is extensive and strong evidence that this can be achieved by cytology-based screening programs, which continue to be the mainstay of cervical prevention worldwide despite their inherent methodological limitations. This article presents a review on the utility of conventional, ancillary and experimental methods for cervical screening both as single tests and test combinations, and describes possible future directions for enhanced screening accuracy using risk-adapted protocols.

Detection of lymphatic invasion in early stage primary colorectal cancer with the monoclonal antibody D2-40.

PURPOSE: The purpose of this study was to investigate the presence of lymphatic invasion detected by D2-40 immunostaining compared to conventional hematoxylin-eosin (HE) staining in primary colorectal cancer (CRC) and the development of focal new lymphangiogenesis and peritumoral lymphatic proliferation in relation to the tumor stages. Additionally, we analyzed the relation of peritumoral inflammatory reaction (PIR) to tumor stages in CRC. The identification of new categories of patients with high-risk CRC would be very helpful in improving treatment strategies and patient outcome especially in early CRC. PATIENTS AND METHOD: Biopsies were taken from 41 patients with colorectal adenocarcinomas at different stages of disease. Immunohistochemistry was performed on paraffin-embedded sections. First, the whole section was screened for the presence of lymphatic invasion and PIR with routine HE staining. After analysis of the HE-stained slides, the slides were destained and reused for immunohistochemistry with the D2-40 monoclonal antibody. D2-40-immunostained sections were screened for the presence of lymphatic invasion, the proliferation of lymphatic vessels and focally newly developed lymph vessels. RESULTS: Using the D2-40 antibody for immunostaining, our results demonstrate a significantly higher detection (p < 0.05) of lymphatic vessel invasion compared to routine HE staining in primary CRC. 22% more patients with lymphatic vessel invasion could be identified compared to routine HE staining, especially in node-negative tumor stage (UICC II). The positive predictive value of lymphatic invasion evaluated by D2-40 immunostaining to predict lymph node metastasis is 92% (negative predictive value 81%). High PIR was shown in UICC stage I and II. These infiltrations were rarely seen in UICC stage III and were absent in UICC stage IV. Higher UICC tumor stage is associated with a higher rate of focally newly developed lymphatic vessels. In UICC stage I we found peritumoral lymphatic vessel proliferation only in one case (14%) and in UICC stage II no case was found. 47% of the cases in UICC stage III and 50% of the cases in UICC stage IV showed focal peritumoral lymphatic vessel proliferation. CONCLUSIONS: Immunostaining with D2-40 significantly increased the detection rate of lymphatic invasion compared to conventional HE staining in primary CRC. The D2-40 antibody specific for lymphatic endothelium cells has the potential for a prognostic marker in early stage CRC. Further prospective studies are necessary to evaluate the prognostic value of lymphatic invasion and the induction of tumor lymphangiogenesis and its role in human cancer progression.

HPV in anal squamous cell carcinoma and anal intraepithelial neoplasia (AIN). Impact of HPV analysis of anal lesions on diagnosis and prognosis.

BACKGROUND AND AIMS: Majority of cases of anal squamous cell carcinoma are human papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia (AIN). This study was conducted to examine methods which may enable the routine diagnosis of HPV-induced changes in the anal rim and the consequences of such detection especially in view of a more sensitive diagnosis of AIN. Results were clinically correlated. METHODS: The study included biopsy samples from 87 patients who had been diagnosed with the following disease patterns: 47 invasive anal carcinoma, 33 AIN of varying severity and seven condylomatous lesions. In 52 of these cases, a tumour was clinically suspected. All biopsies were retrospectively examined for microscopic indications of HPV infection. After microdissection, additional HPV analysis via PCR was carried out. RESULTS: In 38 of 47 cases of anal carcinoma, HPV DNA could be detected via PCR (80.9%), the majority of which were HPV 16 (33/38=86.8%). In 29 of the 33 cases of AIN, HPV DNA was detected (87.9%), most of these in AIN III (15/16=93.8%). Histological markers of HPV infection were detected in all 87 cases. DISCUSSION: In our series, the clinical diagnosis of the invasive anal carcinoma had a high sensitivity of 93.6%, with a specificity of 80%. The positive predictive value was 84.6%, and the negative predictive value 91.4%. In contrast, AIN had been detected clinically in none of the cases. In this situation, especially with high-risk patients, our findings recommend anal HPV screening in combination with anal cytology and anoscopy. CONCLUSION: Based on our results, we urgently recommend for any histological report on excision of anal lesions to include a statement whether histological markers of HPV infection were detected. In individual cases, validation via HPV PCR must be considered.