Loss of imprinting and loss of heterozygosity on 11p15.5 in head and neck squamous cell carcinomas

Background. IGF2 and H19 are reciprocal imprinted genes with paternal and maternal monoallelic expression, respectively. This is interesting, because IGF2 is known as a growth factor, and H19 encodes a RNA with putative tumor suppressor action. Furthermore, IGF2 and H19 are linked genes located on chromosome 11p15.5, a common site of loss of heterozygosity in human cancers.Methods. We performed an allelic-typing assay using a PCR-RFLP-based method for identification of heterozygous Informative cases in head and neck squamous cell carcinomas. Tumoral total RNA was extracted from each of the heterozygotes and further studied by RT-PCR analysis.Results. We detected the expression of the IGF2 gene in 10 of 10 informative cases. Two cases exhibited LOI of the IGF2 gene as evidenced by biallelic expression, and in another case, LOH was coupled with monoallelic expression of this growth factor. LOI for the H19 gene was observed in 1 of 14 informative samples analyzed. In this case, we also detected parallel mono-allelic expression of the IGF2 gene. Down-regulation of the H19 gene was observed in 10 of 14 cases.Conclusion. These findings support the hypothesis that H19 may be a tumor suppressor gene involved In head and neck carcinogenesis. Furthermore, our data showed that genetic and epigenetic chances at 11p15.5 could lead to abnormal expression of imprinted genes in HNSCC. (C) 2001 John Wiley & Sons, Inc.

Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide

4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the expression of bcl-2 and bax during tongue carcinogenesis induced by 4NQO. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Although no histological changes were induced in the epithelium after 4 weeks of carcinogen exposure, bcl-2 and bax were over-expressed (P < 0.01) in all layers of the 'normal' epithelium. The expression levels were the same in all layers of epithelium for both the antibodies used (bcl-2 or bax). In dysplastic lesions at 12 weeks following carcinogen administration, the levels of bcl-2 and bax expression did not increase when compared to negative control with the immunoreactivity for bcl-2 being restricted to the superficial layer of epithelium. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, bcl-2 was expressed in some cells of tumour islands. on the other hand, immunostaining for bax was widely observed at the tumour nests. The labelling index for bcl-2 and bax showed an increase (P < 0.05) after only 4 weeks of 4NQO administration. In conclusion, our results suggest that abnormalities in the apoptosis pathways are associated with the development of persistent clones of mutated-epithelial cells in the oral mucosa. Bcl-2 and bax expression appears to be associated with a risk factor in the progression of oral cancer.

Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa front 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/ Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors. (C) 2004 Elsevier B.V. All rights reserved.

Detection of HPV in mouth floor squamous cell carcinoma and its correlation with clinicopathologic variables, risk factors and survival

The human papillomavirus (HPV) has been historically associated with head and neck cancers, although its role in oral carcinogenesis remains poorly defined. The purpose of this study was to investigate the prevalence of HPV in mouth floor squamous cell carcinoma and correlate it with clinicopathologic variables, risk factors and survival. HPV presence was evaluated by nested polymerase chain reaction (nPCR) in 29 paraffin-embedded specimens of mouth floor squamous cell carcinoma. HPV DNA was detected in 17.2% (5 of 29) of the specimens; the highest prevalence was observed in non-smoking patients over the age of 60 years. All HPV DNA positive specimens were detected in men with clinical stage III and IV lesions, being most of which were moderately differentiated. Despite this correlation there were no statistically significant differences observed among the analyzed variables, including patients' survival. The relatively low incidence of HPV DNA present in these tumors suggests that this virus does not, by itself, have a significant role in the development of mouth floor squamous cell carcinoma. J Oral Pathol Med (2008) 37: 593-598

Cholangiocarcinoma and Squamous Cell Carcinoma of the Stratified Epithelial Portion of the Stomach in a Horse: A Case Report

Both cholangiocarcinoma and squamous cell carcinoma of the stomach stratified squamous epithelial portion are rarely found in equine medicine despite being more common in human beings, dogs, and cats. The objective of the present article was to report the simultaneous occurrences of these two types of neoplasias in an 11-year-old mare. Numerous firm, whitish nodules were distributed throughout the liver parenchyma and those protruding over its surface were umbilicated in their appearance. It was verified that the nodules adhered to the peritoneum and omentum, diaphragm, spleen, and stomach serosa compressed the adjacent structures. The stomach stratified squamous epithelial portion, particularly originating in the margo plicatus toward the cardia, was covered by numerous smooth, whitish spherules. Microscopic examination allowed the liver, tumor, and the abdominal implants to be identified as a cholangiocarcinoma, and the stomach neoplasia as a carcinoma of its stratified squamous epithelial portion. Considering this as an uncommon finding, although when considered individually, the presence of a cholangiocarcinoma and a squamous cell carcinoma of the stratified squamous epithelial portion of the equine stomach in the same specimen is worthy of reporting. (C) 2011 Elsevier B.V. All rights reserved.

Squamous cell carcinoma in a residual mandibular cyst

Described is a case of squamous-cell carcinoma arising in a residual cyst in a 60-year-old edentulous woman. The clinical and radiographic diagnosis was residual cyst, and the treatment employed was conservative surgical enucleation. The cause of these changes is unknown. Theoretically, the inflammatory reaction may have been a predisposing factor.