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.
The type-specific persistence of oncogenic human papillomavirus (HPV) is considered to be the true precursor of cervical cancer at which the transcription of the viral oncogenes E6 and E7 is necessary for the malignant transformation and maintenance of the neoplastic state. In the present pilot study, a cohort of 66 women was investigated from a routine officebased screening population who had an index cytological result from normal to high-grade squamous intraepithelial lesions and who were also HPV-DNA positive for at least one of the following high-risk HPV types: HPV 16, 18, 31, 33 and 45 detected by MY09/MY11 consensus and GP5 + /6 + general primers, followed by sequencing. The expression of E6/E7 transcripts from the same HPV types was detected by the PreTect HPV-Proofer. Cervical status was checked 18 months after the mRNA test. The expression of E6/E7 mRNA was found in 58% of the cases showing a 97% concordance with the HPV-DNA types and a positive correlation with increasing cytological and histological grade. All HPV-mRNA positive cases were also positive for HPV DNA whereas 25 (38%) of the HPV-DNA positive cases did not express the respective mRNA. The diagnostic validity of the PreTect assay for detecting histologically-proven prevalent CIN3 lesions were: sensitivity 95%, specificity 55%, positive predictive value (PPV) 81% and negative predictive value (NPV) 86%. The prognostic power of the PreTect test for predicting cytological disease progression was as follows: 78% sensitivity, 60% specificity, 37% PPV and 90% NPV. In conclusion, our results showed that the detection of oncogenic HPV E6/E7 mRNA in cervical smears in a routine screening setting identifies prevalent CIN3 lesions with nearly 100% sensitivity and has a very high negative predictive value for disease progression during the natural course of HPV infection. Thus, testing for HPV oncogenic activity may be used as a clinically predictive marker to enhance the net effectiveness of screening and enable the prognostication of prevalent cervical lesions.
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.
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