Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project: confirmation by microarray analysis.

The near completion of the human genome project and the recent development of novel, highly sensitive high-throughput techniques have now afforded the unique opportunity to perform a comprehensive molecular characterization of normal, precancerous, and malignant cells, including those derived from squamous carcinomas of the head and neck (HNSCC). As part of these efforts, representative cDNA libraries from patient sets, comprising of normal and malignant squamous epithelium, were generated and contributed to the Head and Neck Cancer Genome Anatomy Project (HN-CGAP). Initial analysis of the sequence information indicated the existence of many novel genes in these libraries [Oral Oncol 36 (2000) 474]. In this study, we surveyed the available sequence information using bioinformatic tools and identified a number of known genes that were differentially expressed in normal and malignant epithelium. Furthermore, this effort resulted in the identification of 168 novel genes. Comparison of these clones to the human genome identified clusters in loci that were not previously recognized as being altered in HNSCC. To begin addressing which of these novel genes are frequently expressed in HNSCC, their DNA was used to construct an oral-cancer-specific microarray, which was used to hybridize alpha-(33)P dCTP labeled cDNA derived from five HNSCC patient sets. Initial assessment demonstrated 10 clones to be highly expressed (>2-fold) in the normal squamous epithelium, while 14 were highly represented in the malignant counterpart, in three of the five patient sets, thus suggesting that a subset of these newly discovered transcripts might be highly expressed in this tumor type. These efforts, together with other multi-institutional genomic and proteomic initiatives are expected to contribute to the complete understanding of the molecular pathogenesis of HNSCCs, thus helping to identify new markers for the early detection of preneoplastic lesions and novel targets for pharmacological intervention in this disease.

The olfactory loss that accompanies an HIV infection.

A number of studies have shown that HIV infection is associated with decreased olfactory ability. Additionally, it has been hypothesized that a reduced odorant identification may precede the advent of AIDS Dementia Complex (ADC). However, it is not known whether changes in olfactory ability are a manifestation of neurocognitive decline which may precede the appearance of AIDS Dementia Complex, damage to the peripheral olfactory system from opportunistic infection, or whether olfactory structures have a particular sensitivity to HIV. These issues were addressed in a cross-sectional study examining variability in the neuropsychological, neurological, otolaryngological, auditory, and olfactory status in HIV-positive subjects. A stepwise regression provided evidence that the ability to identify odorants was influenced by age, nasal structure and pathology, neurocognitive ability, and level of AIDS Dementia Complex. On the other hand, only nasal pathologies accounted for the variability in olfactory thresholds. These data suggest that identification and thresholds tests may reflect different olfactory pathologies. Additionally, these data suggest at least part of the decline in olfactory ability accompanying an HIV infection may be secondary to nasal pathologies. Because of their rapidly changing neurocognitive status, HIV-positive patients represent an excellent group in which to study the determinants of olfactory ability.

Histopathology of olfactory mucosa in Kallmann's syndrome.

Olfactory mucosa was harvested by intranasal biopsy from a man with Kallmann's syndrome in whom the absence of the olfactory bulbs was documented by magnetic resonance imaging. On electron microscopic examination, several pathologic changes were evident in the olfactory mucosa. First, most olfactory neurons lacked cilia (ie, were morphologically immature). Second, the fila olfactoria had fewer than the normal number of axons, and a large proportion of them were apparently undergoing electron lucent degeneration. Finally, neuromatous collections of axons were seen superficial to the basement membrane in the epithelium. Similar changes have been observed in the mucosa of experimentally bulbectomized rodents. Accordingly, a constellation of pathologic changes--axonal degeneration, neuronal immaturity, and the formation of intraepithelial neuromas--seems to be characteristic of olfactory mucosa that cannot innervate the olfactory bulb in both humans and animals. On the basis of our observations, it is worth investigating the status of the olfactory bulb in other forms of human anosmia in which similar morphological changes are observed in the mucosa, such as persistent posttraumatic anosmia and isolated congenital anosmia.

Coexistent oral cryptococcosis and Kaposi's sarcoma in acquired immunodeficiency syndrome.

As experience with the acquired immunodeficiency syndrome has grown during the last decade, it has become important to recognize interactions between the opportunistic infections and malignancies that complicate the course of patients with acquired immunodeficiency syndrome. Our recent experience as described in this paper reveals that Kaposi's sarcoma and cryptococcal infection can associate in such a manner. The first reported case of oral Cryptococcus neoformans infection within a Kaposi's sarcoma lesion in a patient with acquired immunodeficiency syndrome is described. Based on the clinical course of this patient, it is an important consideration that the sarcoma may have harbored and even protected the fungus during systemic amphotericin B therapy.