Human papillomavirus and salivary gland neoplasia: a p16INK4 immunohistochemical and in situ hybridisation study.

OBJECTIVE: This study aimed to evaluate the association between human papillomavirus infection and salivary gland tumours in a Scottish cohort. METHODS: Specimens from a range of salivary gland tumours operated on between 1997 and 2012 were studied. A tissue microarray constructed from tissue blocks was subjected to p16INK4 (cyclin-dependent kinase inhibitor 2A) immunohistochemistry and in situ hybridisation using probes specific for human papillomavirus, including types 16 and 18. RESULTS: A total of 61 tumours (benign and malignant) were deemed suitable for the study. p16INK4 staining yielded three (4.9 per cent) positive samples: one small cell carcinoma, one squamous cell carcinoma and one poorly differentiated carcinoma. Human papillomavirus in situ hybridisation demonstrated a positive signal in the latter sample only (1.6 per cent). CONCLUSION: This study demonstrated a very low human papillomavirus detection rate in salivary gland tumours. It can therefore be concluded that human papillomavirus infection is unlikely to play a role in salivary gland neoplasia. Rare human papillomavirus positive cases should be carefully evaluated to exclude the possibility of a metastatic lesion.

Ultrastructural study of intranuclear inclusion bodies of pulmonary adenocarcinoma.

Intranuclear inclusion bodies are sometimes observed in pulmonary adenocarcinoma by light microscopy. Electron microscopic characteristics of lung cancer cells with intranuclear inclusion bodies were studied. In addition, polymerase chain reaction (PCR) was performed using primers coding for human papillomavirus (HPV) types 16, 18, and 33. Eosinophilic intranuclear inclusion bodies were observed in 22 out of 285 cases by light microscopy. Immunohistochemically, cancer cell nuclei stained with PE-10. Three types of intranuclear inclusion bodies were classified electron microscopically. Type A showed aggregation of electron dense particles (30-40 nm) with an electron-dense core and was most frequently observed. Type B consisted of a mass of branching and whirling tubular structures. Type B intranuclear inclusions had a relationship with inner nuclear membrane. In type C, several spherical inclusions were observed in one nucleus. HPV DNA was detected using PCR and type-specific probes in a case with type A inclusion bodies. This study suggests that intranuclear inclusion bodies in pulmonary adenocarcinoma are formed by several different mechanisms.

A simian virus 40 large T-antigen segment containing amino acids 1 to 127 and expressed under the control of the rat elastase-1 promoter produces pancreatic acinar carcinomas in transgenic mice.

The simian virus 40 large T antigen induces tumors in a wide variety of tissues in transgenic mice, the precise tissues depending on the tissue specificity of the upstream region controlling T-antigen expression. Expression of mutant T antigens that contain a subset of the protein's activities restricts the spectrum of tumors induced. Others showed previously that expression of a mutant large T antigen containing the N-terminal 121 amino acids (T1-121) under control of the lymphotropic papovavirus promoter resulted in slow-growing choroid plexus tumors, whereas full-length T antigen under the same promoter induced rapidly growing CPR tumors, T-cell lymphomas, and B-cell lymphomas. In those instances, the alteration in tumor induction or progression correlated with inability of the mutant large T antigen to bind the tumor suppressor p53. In the study reported here, we investigated the capacity of an N-terminal T antigen segment (T1-127) expressed in conjunction with small t antigen under control of the rat elastase-1 (E1) promoter to induce pancreatic tumors. The results show that pancreases of transgenic mice expressing T1-127 and small t antigen display acinar cell dysplasia at birth that progresses to neoplasia. The average age to death in these mice is within the range reported for transgenic mice expressing full-length T antigen under control of the E1 promoter. These results indicate that sequestering p53 by binding is not required for the development of rapidly growing acinar cell carcinomas. In addition, we provide evidence that small t antigen is unlikely to be required. Finally, we show that the p53 protein in acinar cell carcinomas is wild type in conformation.

Human papillomavirus type 18 DNA and E6-E7 mRNA are detected in squamous cell carcinoma and adenocarcinoma of the lung.

To provide an accurate evaluation of the association of human papillomavirus (HPV) with lung cancer, 36 cases of lung cancer were analysed for HPV DNAs by polymerase chain reaction (PCR) with dot-blot and Southern blot analyses, and for the transcripts from the E6-E7 transforming region by in situ hybridisation (ISH). HPV-18 DNA was detected in three (8%) of 36 specimens; histologically, in one (10%) of 10 squamous cell carcinomas and two (9%) of 22 adenocarcinomas. Neither HPV-16 nor -33 DNA was detected in any cases examined. Expression of E6-E7 mRNA was confirmed in the cases which contained, HPV-18 DNA. HPV-18 may play an important role in the development and progression of cancer in some cases of both squamous cell carcinoma and adenocarcinoma of the lung.