Expression of the E-cadherin-catenin complex in lung neuroendocrine tumours.

Neuroendocrine tumours (NETs) of the lung represent a wide spectrum of phenotypically distinct entities, with differences in tumour progression and aggressiveness. The redistribution and/or the loss of various cell adhesion molecules, such as the E-cadherin-catenin complex, play a predominant role in carcinogenesis and in tumour invasion. Moreover, mutations in exon 3 of the beta-catenin gene, the adenomatous polyposis coli (APC) gene or the E-cadherin genes were previously found to result in intracytoplasmic and/or nuclear beta-catenin protein accumulation, activating nuclear transcription of target genes involved in tumour progression. In the present study, the distribution of the components of this E-cadherin-catenin complex has been investigated by immunohistochemistry and an attempt has been made to correlate the abnormal expression pattern with the eventual detection of mutations in the corresponding genes. This study included 27 primary NETs of the lung, with nine typical carcinoids (TCs), three atypical carcinoids (ACs), and 15 large cell neuroendocrine carcinomas (LCNECs). The E-cadherin-catenin complex remained expressed in most of these lung tumours, but with a cytoplasmic and/or nuclear redistribution of beta-catenin, E-cadherin, and alpha-catenin; abnormal positive immunoreactivity was observed in 24 (88.9%), in 21 (80.8%), and in 20 (76.9%) NETs, respectively. In the great majority of cases, there was a good correlation between the expression of these three proteins, but no significant association with histological classification or TNM stage. Thus, E-cadherin-complex redistribution cannot be considered a prognostic marker in NET of the lung. Of particular interest was the frequent focal beta-catenin nuclear immunostaining (55.5% in total), which was also unrelated to histological type or TNM stage. However, this study failed to detect any mutation in exon 3 of the beta-catenin gene, in the APC gene or in the E-cadherin gene. These data suggest another mechanism of regulation of beta-catenin in these tumours.

Detection of human papillomavirus DNA in bronchopulmonary carcinomas by hybrid capture II: a study of 185 tumors.

BACKGROUND: Some human papillomaviruses (HPVs) are oncogenic in the cervix and are also associated with benign and malignant proliferations in other organs. Currently, the association of HPV with tumors of the lower respiratory tract is not so clearly defined because the studies are difficult to compare; series of cases reported from different geographic regions have used frozen or formalin fixed samples and a variety of techniques of HPV detection. METHODS: The authors studied the prevalence of HPV in a large series of 185 frozen bronchopulmonary tumor samples with a new solution hybridization technique, Hybrid Capture II assay. This test is largely applied in cervical pathology. Its sensitivity is very close to the sensitivity of PCR. It allows the detection of 18 mucosal HPV types, divided into 1 oncogenic and 1 nononcogenic group. RESULTS: Oncogenic HPV DNA was detected by the Hybrid Capture II assay in 5 cases (2.7%) of 185 (3 males and 2 females). In the rare positive cases detected, the authors could not find any consistent morphologic changes classically associated with HPV infection in anogenital lesions, such as koilocytosis. CONCLUSIONS: Oncogenic HPV DNA is detected in a small proportion of cases of bronchopulmonary carcinoma, and thus HPV infection appears to play a limited role in the tumorigenesis of most lung carcinomas.

Mucosal oncogenic human papillomaviruses and extragenital Bowen disease.

BACKGROUND: Genital Bowen disease is known to have a strong association with human papillomavirus (HPV) type 16. On the other hand, previous studies of extragenital Bowen disease (EBD) that have used different hybridization techniques have produced discordant results in the detection of mucosal oncogenic HPV. METHODS: Ninety-four samples of EBD from 78 patients were investigated clinicopathologically. DNA extracted from fixed and embedded tissues was analyzed for the presence of the main mucosal oncogenic HPV types 16, 18, 31, and 33 using polymerase chain reaction (PCR) with specific primers described in 1996 by Baay et al., which are particularly well adapted to fixed tissues and give small amplimers. Moreover, 11 EBD of the hands were investigated by in situ hybridization (ISH). RESULTS: Of the 94 extragenital BD obtained from 78 patients, HPV DNA type 16 was detected in 78 cases (83%) from 65 patients (83.3%) by PCR. Nine patients with EBD of the hands (90%) had HPV type 16, and ISH displayed a diffuse hybridization pattern that corresponded to the episomal viral form of HPV DNA. CONCLUSIONS: The current retrospective study of 94 samples clearly demonstrates the high prevalence of HPV type 16 infection in EBD, especially in EBD of the hands. In this study, no specific clinical, topographic, or histopathologic features of any lesions were found to be indicative of the presence or absence of HPV.