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The stromal reaction in basal cell carcinomas: A prerequisite for tumour progression and treatment strategy
Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology.
2004 (English)In: British Journal of Plastic Surgery, ISSN 0007-1226, Vol. 57, no 5, 429-439 p.Article in journal (Refereed) Published
Abstract [en]

Specimens of basal cell carcinomas collected from 28 patients were classified into three groups: superficial, nodular, and infiltrative, according to their microarchitecture. The specimens were then subjected to histological characterization by means of a biotinylated hyaluronan-binding probe (HABP). By using Ki-67 and PCNA the proliferative activity of the BCC tumours was evaluated with immunohistological techniques. In superficial BCC the tumour islands displayed moderate hyaluronan (HA) staining. Feeble proliferation, denoted by modest mitotic activity and weak Ki-67 and PCNA immunoreactivity, occurred within the tumour islands. The surrounding connective tissue resembled normal skin, and no differentiated tumour stroma was observed. In nodular BCC, the HA staining of the tumour strands was weak to moderate, denoting increased proliferative activity. The differentiated surrounding tumour stroma stained strongly for HA. Tumour islands of infiltrative BCC stained weakly to moderately to HA and evidenced intense proliferation. The intensely HA-stained tumour stroma ended abruptly and the adjacent areas were almost devoid of HA. This study showed that the proliferative activity of BCC cells is associated with increased expression of HA in the tumour stroma. Modification of tumour-associated connective tissue indicates a close relationship between the tumour cells and the adjacent matrix. In particular, in infiltrative BCC, such alterations include degeneration and possible modification and remodelling of the surrounding extracellular matrix. These processes involving areas of probable importance for tumour progression, should be considered when deciding the extent of intended surgical resection.

Place, publisher, year, edition, pages
2004. Vol. 57, no 5, 429-439 p.
Keyword [en]
Carcinoma; Basal Cell/*pathology, Cell Division, Disease Progression, Humans, Immunohistochemistry/methods, Ki-67 Antigen/metabolism, Proliferating Cell Nuclear Antigen/metabolism, Skin Neoplasms/*pathology
URN: urn:nbn:se:umu:diva-7784DOI: 10.1016/j.bjps.2003.12.024PubMedID: 15191824OAI: diva2:147455
Available from: 2008-01-12 Created: 2008-01-12 Last updated: 2009-12-09Bibliographically approved
In thesis
1. Impaired reparative processes in particular related to hyaluronan in various cutaneous disorders: a structural analysis
Open this publication in new window or tab >>Impaired reparative processes in particular related to hyaluronan in various cutaneous disorders: a structural analysis
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cutaneous reparative processes, including wound healing, are highly developed procedures in which a chain of actions occurs to reconstitute the function of the wounded tissue. To prevent a delayed or excessive reparative process it is important to understand how this procedure develops and is maintained. One of the major extracellular matrix components of the skin is the glycosaminoglycan hyaluronan (HA). HA contributes to an extracellular environment, which is permissive for cell motility and proliferation, features that may account for HA’s unique properties observed in scarless foetal wound healing. The molecule is found at high concentration whenever proliferation, regeneration and repair of tissue occur.

The aims of the present studies were to analyse the distribution of HA and to investigate its possible role in various cutaneous conditions associated with an impaired reparative process like in scar tissue formation in healing wounds, changed skin characteristics in diabetes mellitus and proliferating activity in basal cell carcinomas.

Tissue biopsies were obtained from healthy human skin, type-I diabetic skin and various scar tissues. The samples were analysed in the light microscope with a hyaluronan-binding-probe, antibodies for collagen I, III, PCNA and Ki-67. Ultrastructural analyses were performed on the same tissue samples.

In normal skin HA was present mainly in the papillary dermis. In epidermis HA was located in between the keratinocytes in the spinous layer. In the different scar tissues the localization of HA varied, with an HA distribution in mature scar type resembling that in normal skin. In keloids the papillary dermis lacked HA, but the thickened epidermis contained more HA than the other scar types. Ultrastructural studies of keloids revealed an altered collagen structure in the dermal layers, with an abundance of thin collagen fibers in the reticular dermis and thicker collagen fibers in the papillary dermis. Furthermore, the keloids displayed epidermal changes, which involved the basement membrane (BM), exhibiting fewer hemidesmosomes, and an altered shape of desmosomes in the entire enlarged spinous layer. These alterations in epidermis are suggested to influence the hydrodynamic and cell regulatory properties of the wounded skin.

In diabetic patients, a reduced HA staining in the basement membrane zone was seen. The staining intensity of HA correlated to the physical properties of the skin reflected by their grades of limited joint mobility (LJM). Furthermore, the HA staining correlated with serum concentration of the HbA1c.

In basal cell carcinomas (BCC), HA occurred predominantly in the tumour stroma. The distribution was most intense in the highly developed superficial BCC type, and resembled that of the papillary dermis of normal skin. In contrast, in the infiltrative BCC type, the tumour stroma stained weakly in the infiltrative part of the tumour. Moreover, the surrounding dermal layer was deranged and devoid of HA. The findings suggest that the tumour stroma in superficial BCC causes a slow, well-regulated cell growth in which the tumour cells do not substantially disturb the normal skin function. In the infiltrative BCC type, the tumour cells cause a disintegration of the tumour stroma as well as the normal surrounding dermis, which permits further spreading of the tumour. In fact, the behaviour of the infiltrative BCC tumour, growing beyond its boundaries, resembles that of the keloid.

The mapping of the distribution of HA could be a useful tool for prognostic information, for evaluating the degree of progress and for deciding the choice of treatment in various diseases of the skin. In skin malignancies such as BCC it can be used to determine the radicality at the surgical excision of the tumour.

Keywords: Hyaluronan, scar tissue, diabetes mellitus, basal cell carcinoma, skin, wound healing

53 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 892
hyaluronan, scar tissue, diabetes mellitus, basal cell carcinoma, skin, wound healing
Research subject
urn:nbn:se:umu:diva-276 (URN)91-7305-652-9 (ISBN)
Public defence
2004-05-27, Sal B, Byggnad 1 D, Tandläkarhögskolan, 9 tr, NUS, Umeå, 09:00 (English)
Available from: 2004-05-11 Created: 2004-05-11 Last updated: 2009-12-08Bibliographically approved

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