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Basement membrane changes and Langerhans cell alterations during tumour development


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Mc Ardle, John Patrick 1988 , 'Basement membrane changes and Langerhans cell alterations during tumour development', MD thesis, University of Tasmania.

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This thesis examines tumour development from two separate
Firstly, with regard to basement membrane changes in tumour
development, this study confirms the prior observation that tumour
cells, both in the primary focus and in metastatic deposits, are
capable of producing an intact and continuous basement membrane.
Assessment as to whether or not a given tumour is invasive, then,
requires correlation between the integrity of the basement membrane
and the tissue architecture. The mere presence of an intact basement
membrane does not mean that a tumour is in an "in—situ" phase if the
tissue architecture is that of an invasive carcinoma. In metastatic
deposits of epithelial tumours the development of a new basement
membrane appears to be dependent upon interaction with mesenchymally
derived connective tissue suggesting that the normal formation of
epithelial basement membrane requires interaction with stromal
connective tissue. In metastatic carcinoma, as in primary tumours
(Albrechtsen et al., 1986) the redevelopment of extracellular basement
membrane is related to the degree of tumour, cell differentiation.
The abrupt loss of basement membrane associated with a focus
of invasive tumour growth , seen particularly in nodular basal cell
carcinoma, supports the concept that the basement membrane, though
flexible, is continuous, insoluble and impermeable to cell movement.
Expansion of an intact basement membrane may be seen in superficial
spreading basal cell carcinoma and early nodular basal cell carcinoma
which therefore, by definition, may be regarded as in—situ tumours.
The advent of the immunoperoxidase method, which can be used
on paraffin—processed tissue, by allowing the detection of subtle
histologic changes, has clarified observations previously noted in the
literature on early tumour development. The variation in thickness of
the basal lamina in epidermal tumours, previously noted by Frappart et
al. (1982), we now believe to be an artefact due to tangential
sectioning of the basement membrane. Globular fragments staining
positively for laminin and type IV collagen noted by Weber et al.
(1982) and van Cauwenberge et al. (1983), in basal cell carcinoma
prove to be incorporated stroma and accompanying basal lamina and are
not due to defective basement membrane formation by the tumour cells.
Secondly, with regard to Langerhans cell changes in in—situ
and invasive neoplasia, this study has shown that the Langerhans cell
density is significantly increased in intraepidermal carcinoma—in—situ
(Bowen's disease), cervical intraepithelial neoplasia, and invasive
neoplasms, including squamous cell carcinoma, basal cell carcinoma and
keratoacanthoma, when compared to normal epidermis. In addition the
Langerhans cell density increases in cervical intraepithelial
neoplasia correlating with the severity of the intraepithelial lesion.
This increase in Langerhans cell density suggests activation of a
local immune mechanism and is supportive evidence for the concept that
Langerhans cells play a role in tumour surveillance.
In addition to being increased within neoplastic lesions,
the Langerhans cell density was also found to be increased in
epithelium adjacent to the neoplasm in both skin and cervix,
suggesting either that the neoplastic lesion is producing a
chemotactic factor which diffuses into the adjacent epithelium or that
the adjacent morphologically normal epithelium is functionally
Langerhans cell density is decreased in cervical wart virus
infection and in koilocytic dysplasia and this depletion appears to be
related to viral expression rather than to the presence of viral DNA.
This finding supports the recent suggestion that human papilloma virus
(HPV), the causative agent in cervical wart virus infection, is
involved in cervical carcinogenesis as a tumour promoter. Tumour
promotion by the human papilloma virus may act both through
stimulation of epithelial cell proliferation and through a reduction
in Langerhans cell immunosurveillance.
Two indirect results of the study include:- 1) the
development of a double-staining technique to facilitate
differentiation between Langerhans cells and melanocytes in fresh
human skin; this procedure is based on the ability of anti-S100
antibody to stain both epidermal Langerhans cells and melanocytes,
while L-Dopa stains only melanocytes; and 2) the conclusion that under
conditions of varying epithelial thickness Langerhans cell density
should be estimated per unit length of surface epithelium in order to
determine whether or not there has been a change in Langerhans cell
density in abnormal epithelium.
Although this study has answered some questions, many more
have arisen, ttie solution of which should add greatly to our
understanding of early tumour development both in its in-situ and
invasive phases.

Item Type: Thesis - MD
Authors/Creators:Mc Ardle, John Patrick
Keywords: Membranes, Basement, Pathology, Cellular
Copyright Holders: The Author
Copyright Information:

Copyright 1988 the Author - The University is continuing to endeavour to trace the copyright
owner(s) and in the meantime this item has been reproduced here in good faith. We
would be pleased to hear from the copyright owner(s).

Additional Information:

Thesis (M.D.)--University of Tasmania, 1988. Includes bibliographies

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