Cell death does not herald epithelial involution ("atrophy") in oral sub mucous fibrosis: a TEM study.

ABSTRACT

The disease progression in oral submucous fibrosis (OSF) seems to be in a biphasic manner, along both fibroblastic and keratinocytic lineages. The epithelial malignancy is considered to be a sequel of connective tissue changes. "Atrophy" of epithelium makes it amenable to the effect of oral carcinogens. This concept looks rather simplistic in the light of the current understanding of epithelial cell biology. So the concept of epithelial "atrophy" needs redressal against the backdrop of recent investigations. 12 cases of clinically and histologically advanced OSF cases (MF = 48) who were habitual areca-quid chewers comprise the study group. 5 (MF=14) non-OSF, non-areca-nut chewing healthy volunteers, constituted the control group. Biopsy was done and the sections were processed for light and electron microscopy. Cell countings were made based on established criteria for apoptosis and necrosis under the high resolution of a TEM and electron micrographs were taken. The Apoptotic Index (A1) calculated for the diseased mucosa was 3.0 +/- 1.3 and for the control was 2.1 +/- 1.5 (X2 = 1.21, df= 1, p>0.05). The necrotic indices (NI) were respectively, 2.5 +/- 0.6 and 2.0 +/- 1.3 (X2 = 0.24, df = 1, p>0.05). The Absolute Cell death Index (ACI), which is the cumulative figure of apoptosis and necrosis indices, was 5.5 and 4.2 respectively for diseased and normal samples (X2 = 1.8, df = 1, p>0.05). The inability to compute an increased ACI in OSF epithelium, when compared to normal, goes against the concept of epithelial "atrophy". Atrophy envisages an increased apoptotic cell death of keratinocytes, induced by the same signals that caused atrophy and this may contribute to loss of cell of an entire organ. This basic concept in pathology seems to be unfounded with disease. This prompted us for an alternative concept in favour of a reduced proliferation index of the adult stem cell compartment of the oral epithelium. So this study favours the concept of epithelial hypoplasia, rather than atrophy, which causes thinning of surface epithelium in advanced OSF.