Carcinoid tumour associated with enterovirus infection.

Enteroviruses commonly infect the gastrointestinal tract, and replication of enteroviruses has been well documented in the Peyer patches of the small bowel. Chronic enterovirus infection has been found in the stomach and terminal ileum of patients with myalgic encephalomyelitis/chronic fatigue syndrome. The authors report the unexpected finding of enterovirus VP1 protein, by immunoperoxidase staining, in carcinoid tumours found in one patient with myalgic encephalomyelitis/chronic fatigue syndrome and another patient with chronic lower quadrant abdominal pain, and suggest a possible association between enteroviruses and tumorigenesis.

Unique susceptibility of a human lung carcinoid tumor cell line to infection with BK virus.

Carcinoid syndrome is caused by the unregulated secretion of bioactive amines from neuroendocrine tumors arising primarily in the gastrointestinal tract and lungs. The incidence of carcinoid syndrome is 1-2/100,000 and the syndrome is thought to be increasing. Carcinoid tumors are relatively slow growing but can become highly metastatic. Currently, there is no effective therapy to inhibit cell proliferation or metastasis of neuroendocrine tumor (NET) disease. Polyomaviruses are a family of viruses that are able to transform cells and promote tumor formation. In this study, the polyomaviruses SV40, JCV, and BKV were used to assess the ability of polyomaviruses to productively infect a range of human carcinoid cell lines. Infection was assessed by the immunofluorescence detection of T antigen and V antigen. Viruses and cell lines that exhibited productive infections were subsequently assayed by FACS analysis for cell binding and dual promoter luciferase assay for early and late promoter activity. Most carcinoid cell lines were not susceptible to infection by polyomaviruses. However, BKV efficiently infected the pulmonary carcinoid H727 cell line but did not infect a control, non-carcinoid lung cell line (A549). BKV was found to bind to both the susceptible H727 cells and to the non-susceptible A549 cells but viral genes were only efficiently expressed in the H727 cell line. The data demonstrate that BKV can infect human pulmonary carcinoid cells. Infection does not seem to be solely mediated by the virus' ability to bind to cells, as the virus will also bind to non-carcinoid control cells. Both early and late gene expression are supported by the pulmonary carcinoid cells.

Neuroendocrine carcinoma of the uterine cervix: A clinicopathologic retrospective study of 31 cases with prognostic implications.

The present study describes 31 clinical cases of neuroendocrine cervical carcinoma (NECC) treated at Mackay Memorial Hospital between January 1, 1991 and October 31, 2003. There are two cases of atypical carcinoid tumor (ACT), four cases of large-cell neuroendocrine carcinoma (LCNEC), and 25 cases of small-cell neuroendocrine carcinoma (SCNEC). Overall survival did not differ significantly in relation to surgery, tumor histology, age, FIGO stages, chemotherapeutic regimens or lymph node involvement. The specimens available did not permit HPV (human papillomavirus)-DNA analysis in 5 cases (5/31, 9.7%). The HPV viral infection was absent in 8 cases (8/31, 26%); 17 cases of HPV-18 (17/31); and 1 case of HPV-16 (1/31). The prognosis between mixed and pure type histologic patterns is not significant. The mean survival time for all patients was 32.3 months. The 2-year and 5-year survival rates were 54.8% and 31.5% for all patients. The results of this study reaffirm the biologically aggressive nature of this rare malignancy, its low survival rate, and its very unpredictable prognostic factors. Effective treatments of neuroendocrine cervical tumor still remain inconclusive. Further efforts are still required to identify prognostic factors for this uncommon disease.

Detection of oncogenic virus genomes and gene products in lung carcinoma.

We investigated a series of 122 cases of small cell lung carcinomas and non-small cell lung carcinomas for the presence of several viruses that are known to be oncogenic in humans. Thus, viral genomes (DNA) and/or RNA transcripts and/or proteins of human papillomaviruses (HPV) 16, 18, 31, 33, 51, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), human cytomegalovirus (HCMV) and simian virus 40 (SV40) were investigated on tissue sections (prepared in tissue microarrays) with different techniques of immunohistochemistry and in situ hybridisation. None of the cases displayed a single positive tumour cell for all the viruses tested whatever the technique applied. Of note, in five cases of tumours with lymphoid infiltrates, we detected scattered EBV (EBER)-positive bystander lymphocytes. In three cases, a faint nuclear staining was found with the anti-latent nuclear antigen/LANA1 (HHV-8) antibody. These cases were checked by PCR with two sets of primers (orf 26 and orf 75) and remained negative for this latter virus. Taken together, our data strongly suggest that the conventional human oncogenic viruses (HPV, EBV, HCMV, HHV-8 and SV40) are unlikely to play some role in the development of lung carcinomas..

A case of Epstein-Barr Virus (EBV)-associated thymic carcinoid and investigation of existence of EBV-infected cells in thymus and thymic tumors.

We describe the first case of Epstein-Barr virus (EBV)-associated thymic carcinoid tumor found by in situ hybridization (ISH) on paraffin-embedded sections. ISH revealed that both tumor cells and infiltrated lymphocytes were EBV positive, while a few EBV-infected lymphocytes were detected in 2 of 11 thymuses and 1 of 11 thymomas.

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.