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Detection of Candida albicans ADH1 and ADH2 mRNAs in human archival oral biopsy samples

Bakri MM, Cannon RD, Holmes AR, Rich AM

J Oral Pathol Med, 2014 Oct;43(9):704-10.
PMID: 24931506 DOI: 10.1111/jop.12193

The aim of this study was to investigate the relationship between expression of Candida albicans alcohol dehydrogenases (ADH) genes in archival formalin-fixed paraffin-embedded (FFPE) samples from biopsies of leukoplakia.
In vitro expression of Candida albicans alcohol dehydrogenase genes involved in acetaldehyde metabolism

Bakri MM, Rich AM, Cannon RD, Holmes AR

Mol Oral Microbiol, 2015 Feb;30(1):27-38.
PMID: 24975985 DOI: 10.1111/omi.12064

Alcohol consumption is a risk factor for oral cancer, possibly via its conversion to acetaldehyde, a known carcinogen. The oral commensal yeast Candida albicans may be one of the agents responsible for this conversion intra-orally. The alcohol dehydrogenase (Adh) family of enzymes are involved in acetaldehyde metabolism in yeast but, for C. albicans it is not known which family member is responsible for the conversion of ethanol to acetaldehyde. In this study we determined the expression of mRNAs from three C. albicans Adh genes (CaADH1, CaADH2 and CaCDH3) for cells grown in different culture media at different growth phases by Northern blot analysis and quantitative reverse transcription polymerase chain reaction. CaADH1 was constitutively expressed under all growth conditions but there was differential expression of CaADH2. CaADH3 expression was not detected. To investigate whether CaAdh1p or CaAdh2p can contribute to alcohol catabolism in C. albicans, each gene from the reference strain C. albicans SC5314 was expressed in Saccharomyces cerevisiae. Cell extracts from an CaAdh1p-expressing S. cerevisiae recombinant, but not an CaAdh2p-expressing recombinant, or an empty vector control strain, possessed ethanol-utilizing Adh activity above endogenous S. cerevisiae activity. Furthermore, expression of C. albicans Adh1p in a recombinant S. cerevisiae strain in which the endogenous ScADH2 gene (known to convert ethanol to acetaldehyde in this yeast) had been deleted, conferred an NAD-dependent ethanol-utilizing, and so acetaldehyde-producing, Adh activity. We conclude that CaAdh1p is the enzyme responsible for ethanol use under in vitro growth conditions, and may contribute to the intra-oral production of acetaldehyde.
Fulltext Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma

Mohd Bakri M, Mohd Hussaini H, Rachel Holmes A, David Cannon R, Mary Rich A

J Oral Microbiol, 2010 Dec 21;2.
PMID: 21523221 DOI: 10.3402/jom.v2i0.5780

BACKGROUND: Tobacco and alcohol are risk factors associated with cancer of the upper aerodigestive tract, but increasingly the role of infection and chronic inflammation is recognized as being significant in cancer development. Bacteria, particularly Helicobacter pylori, and viruses such as members of the human papilloma virus family and hepatitis B and C are strongly implicated as etiological factors in certain cancers. There is less evidence for an association between fungi and cancer, although it has been recognized for many years that white patches on the oral mucosa, which are infected with Candida, have a greater likelihood of undergoing malignant transformation than those that are not infected.
OBJECTIVE: This article reviews the association between the development of oral squamous cell carcinoma in potentially malignant oral lesions with chronic candidal infection and describes mechanisms that may be involved in Candida-associated malignant transformation.
Fulltext Exophytic Verrucous Hyperplasia of the Oral Cavity – Application of Standardized Criteria for Diagnosis from a Consensus Report

Zain RB, Kallarakkal TG, Ramanathan A, Kim J, Tilakaratne WM, Takata T, et al.

Asian Pac J Cancer Prev, 2016 01 09;17(9):4491.
PMID: 27865210 DOI: 10.7314/APJCP.2016.17.(9).4491

Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions
including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous
leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a
viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or
by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as
verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary
squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC)
need to be further clarified for better understanding of their predictable biologic behavior and appropriate
treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to
the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous
hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical
features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a
PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of
the ‘First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral
Cavity’ held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named
‘Exophytic Verrucous Hyperplasia’. Previously described clinical features of OVH such as the ‘blunt’ or ‘sharp’
variants; and the ‘mass’ or ‘plaque’ variants can now collectively fall under this newly described entity. This paper
discusses in detail the application of the standardized criteria guidelines of ‘Exophytic Verrucous Hyperplasia’
as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool
of OVH cases and facilitate a better understanding of OVH malignant potential.