Alteration in keratinocyte ganglioside content in basal cell carcinomas.

We examined the ganglioside content of normal human keratinocytes and basal cell carcinomas (BCC). The total ganglioside content of the epidermis was 0.098 +/- 0.01 microgram lipid-bound sialic acid/mg dry weight. GM3 was the predominant ganglioside of epidermis. GM2 and GD3 were also found in significant amounts. Polysialylated gangliosides were identified in only small amounts. In contrast to all other body locations, breast epidermis showed large amounts of GM1. The total ganglioside content of nodular and sclerosing facial BCC was approximately 3.5 times that of normal facial epidermis. This marked elevation of total ganglioside was not affected by dermal ganglioside contamination, because the total ganglioside content of the dermis was similar to that of the epidermis. The relative percentage of GM2 was significantly decreased, whereas the relative percentage of GM3 was slightly decreased in BCC. 9-O-acetyl-GD3 was present in the BCC, but not in normal epidermis or dermis. 9-O-acetyl-GD3 may be a surface marker for BCC. Furthermore, the alterations in amount and composition of individual gangliosides on neoplastic membranes may lead to novel therapeutic interventions.     

Expression of EGF receptor,involucrin, and cytokeratins in basal cell carcinomas and squamous cell,carcinomas of the skin

Summary The distribution of several markers of keratinocyte differentiation was studied in normal epidermis, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs) using the immunoperoxidase technique on frozen sections of punch biopsy specimens. As markers a panel of chain-specific monoclonal antibodies (MoAbs) directed against cytokeratin (CK) 4, 8, 10, 13, 18, and 19, a polyclonal antiserum against involucrin, as well as a MoAb against the epidermal growth factor (EGF) receptor were used. In 15 out of 19 BCCs tested, expression of CK 8 was seen. Only a few individual cells in a limited number of BCCs showed positive staining for CK 4, 18, or 19. No expression of CK 10 was seen except for some foci of cell keratinization. Involucrin was not found in BCCs except for some squamous horn cysts. In all BCC cells expression of EGF receptor was found. In the suprabasal layers of normal epidermis from SCC patients, positive staining for CK 10 was seen. A few individual cells in a limited number of SCCs showed positive staining for CK 4, 8, or 18. Involucrin was expressed in the center of SCCs and in the upper layers of normal epidermis. Expression of EGF receptor was found in all SCC cells. These results demonstrate differences in cellular origin and differentiation between BCC and SCC.     

Expression of stromelysin 3 in basal cell carcinomas.

Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.     

Expression of CD44 isoforms in basal cell carcinomas

The expression of CD44 isoforms (CD44std, CD44v6, CD44v10) was investigated by an immuno-histochemical technique in 42 basal cell carcinomas (BCC) of the superficial and nodular variety. All BCCs studied displayed very low amounts of CD44std, a receptor for hyaluronic acid. Except for single CD44std-positive cells located preferentially in the central parts of the BCC nests, the bulk of the tumour formations were CD44std-negative. CD44v6 showed a heterogeneous distribution pattern accentuated in the peripheral palisading tumour cells. In superficial BCCs, the labelling intensity for CD44v6) increased with the size of the tumour nests. CD44v10 was not detectable in BCCs Our findings support the notion that CD44v6 is not linked to the metastatic proclivity of tumours originating from keratinocytes. We suggest that the very low expression of the receptor for hyaluronic acid (CD44std) may be one of the factors which block the formation of metastases from BCCs.     

Ras oncogene mutations in basal cell carcinomas and squamous cell carcinomas of human skin

Activated ras oncogenes have been detected in a variety of human malignancies. Activation of ras oncogenes usually occurs by point mutations within specific codons of the H-ras, N-ras, and K-ras genes. For the present study, DNA was isolated from 30 basal cell carcinomas (BCC) and 12 squamous cell carcinomas (SCC). After amplification of genomic DNA by using the polymerase chain reaction, the occurrence of point mutations was investigated with 32P-labeled synthetic oligonucleotides. These probes are complementary to the known point-mutated nucleotide sequences of the ras genes. In four out of the 30 BCC studied, point mutations were detected at codon 12 of the K-ras gene and at codon 61 of the H-ras gene. The K-ras mutations involve glycine to cysteine and glycine to asparagine amino acid changes. The mutation at codon 61 of the H-ras gene is consistent with a replacement of glutamine by histidine. In one SCC, a point mutation was detected at codon 12 of the K-ras gene, involving a glycine to cysteine substitution in the gene product. These findings demonstrate that mutational activation of ras genes takes place in skin carcinomas, but the rate at which these mutations occur seems to be relatively low.     

Squamous epithelial and basal cell carcinomas in naevus sebaceus (Jadassohn)

Investigation of 181 nevi sebacei (Jadassohn) revealed the development of basal cell carcinoma in 21 cases, prickle-cell carcinoma in 1 patient. 2 basal cell carcinomas had been taken from different parts of the same systematized nevus. All these secondary tumors had developed in postpubertal patients.     

角质形成细胞μ-阿片受体表达的研究

目的：研究不同特性的角质形成细胞μ-阿片受体的表达情况。方法：以体外培养的角质形成细胞株HaCaT细胞、人鳞状细胞癌(简称鳞癌)细胞株A431、神经母细胞瘤SK-N-SH细胞株为对象，采用逆转录(RT)-PCR方法研究细胞μ-阿片受体的表达。结果：在常规体外培养条件下，角质形成细胞株HaCaT细胞、人鳞癌细胞株A431的RT-PCR结果显示有μ-阿片受体mRNA的表达，后者的表达水平略高于前者。结论：μ-阿片受体在角质形成细胞的表达，为神经系统和皮肤通过神经肽直接发生作用提供依据。     

Expression of p27kip1 in basal cell carcinomas and trichoepitheliomas

Immunohistochemical analysis was used to evaluate p27kip1 expression in normal hair follicles and in a series of 39 basal cell carcinomas (BCC) (13 of superficial type, 7 infiltrating, 7 morphea-like, 12 nodular) and 20 trichoepitheliomas (TE) (9 of classic type, 9 immature, 2 desmoplastic). The labeling index (LI) was derived semiautomatically by means of a computer-assisted cellular image analyzer, and statistical analysis was carried out using the Student t test. A positive reaction for p27kip1 was detected in the hair germ papillae, in supramatrical cells, and in the inner pilar sheath, whereas matrical cells and the outer pilar sheath were negative. All BCC and TE cases showed a positive immunoreaction for p27kip1, but the staining pattern was different in the two groups of lesions, being patchy with focal peripheral accentuation in TE and more diffusely dispersed in BCC. The quantitative study showed lower p27kip1 expression in BCC (LI = 27.51 +/- 12.55) than in TE (LI = 45.27 +/- 20.27) (P < 0.0001). Statistically significant differences were also observed between TE subgroups and nodular or infiltrating BCC subtypes. The occurrence of a wide overlap of LI values hampers the practical application of a p27kip1 LI in the differential diagnosis between BCC and TE in difficult cases, however.     

The detection of basal cell determinants in human basal cell carcinomas using two different monoclonal antibodies

This report deals with the reaction pattern(s) of two monoclonal antibodies (MoAbs) with normal skin and basal cell carcinomas (BCC). Using indirect immunoperoxidase (IIP) and indirect immunofluorescence (IIF) techniques, MoAb 12 G7 was observed to react with a determinant related to the cell membrane of the epidermal basal cells. In the IIP technique MoAb 12 G7 showed a positive reaction with 32 out of 34 BCC (94%), while in IIF all the 14 BCC that were studied were positive. In most cases only the cells at the periphery of the tumour nests were stained. MoAb 253 B7 reacted with cytoplasmic determinant(s) of the epidermal basal cells both in the IIF as well as in the IIP techniques. Using the IIP technique only 5 out of 34 BCC (15%) showed a positive reaction with this MoAb. Four of the 5 positively staining tumours showed aggressive histological features. Using IIF technique only 2 out of 14 BCC were positive. The results presented in this communication are discussed with regard to the possible expression of selective differentiation and tumor-associated determinant(s) in BCC.     

盐酸博宁霉素对人表皮角质形成细胞、宫颈鳞癌细胞和表皮癌细胞增殖的影响

目的:探讨盐酸博宁霉素对人角质形成细胞HaCaT、人宫颈上皮癌细胞HeLa及人表皮癌细胞A431增殖的影响.方法:采用MTT法检测盐酸博宁霉素处理后培养的HaCaT细胞、HeLa细胞和A431细胞的增殖率.结果:盐酸博宁霉素能剂量依赖性抑制HaCaT细胞和HeLa细胞的增殖,IC50值分别为11.57 μg/mL和16.47 μg/mL, 但对A431细胞增殖的抑制作用较弱.结论:盐酸博宁霉素的细胞毒性是抗尖锐湿疣药物的治疗学基础.     

Expression of activation antigens by T cells infiltrating basal cell carcinomas

The association of T lymphocytes and dendritic cells with the stromal mononuclear cell response to basal cell carcinomas has led to speculation that cellular immunity may, in part, regulate the growth and development of this neoplasm. It has not been established, however, whether these T cells are functionally competent, or simply coincidental bystanders. We examined the immunologic phenotypes of mononuclear cells in 32 lesions of basal cell carcinoma obtained from 26 patients. The majority of infiltrating mononuclear cells were T cells that were equally distributed between the helper/inducer (Leu 3a+) and cytotoxic/suppressor (Leu 2a+) subtypes; a minority of cells were dendritic and expressed Leu 6 antigen. Virtually all T cells and dendritic cells were HLA-DR+, and many (greater than 30%) of the T cells expressed antigens consistent with stages of ongoing activation (T9, T10). TS2/7, a novel monoclonal antibody recently documented to identify activation-specific subcomponents of 210/165/130 kD glycoprotein complex present on the surface of mitogen- or alloantigen-stimulated human T cells, was also used. Greater than 50% of the T cells observed were TS2/7+. These observations provide in situ immunomorphologic evidence of stromal T cell activation in association with basal cell carcinomas, and suggest a role for active and ongoing cellular immune mechanisms as a determinant of local biological behavior of this neoplasm.     

Epiligrin is decreased in papulonodular basal cell carcinoma tumor nest basement membranes and the extracellular matrix of transformed human epithelial cells

Abstract Patients with anti-epiligrin cicatricial pemphigoid have anti-basement membrane autoantibodies that immunoprecipitate a set of disulfide-linked human keratinocyte polypeptides that co-migrate in sodium dodecyl sulfate polyacrylamide gel electrophoresis with the same complex identified by monoclonal anti-epiligrin (P1E1) and monoclonal anti-nicein/kalinin (GB3) antibodies. In an attempt to further compare the reactivity of patient autoantibodies, P1E1 and GB3, these reagents were tested against the tumor nest basement membranes of 7 papulonodular basal cell carcinomas. These studies found that all of these reagents showed markedly decreased or no reactivity against this substrate. Though their concordant lack of reactivity failed to distinguish these antibodies, these studies did identify a significant defect in papulonodular basal cell carcinoma tumor nest basement membranes. Similarly, integrin subunits α₆, β₄, α₃. and α₂ as well as bullous pemphigoid antigens 1 and 2 (all potential receptors for the extracellular matrix ligands epiligrin and nicein/kalinin) were also reduced in these tumor nest basement membranes. These findings signify an extensive impairment in the lamina lucida of this neoplasm's basement membrane. Related comparative studies of normal human keratinocytes and transformed human epithelial cell lines (specifically, A-431 and HaCat cells) showed that epiligrin production is markedly decreased in the latter. Decreased expression of epiligrin and nicein/ kalinin in papulonodular basal cell carcinoma tumor nest basement membranes in vivo and transformed epithelial cells in vitro indicate that this complex is a transformation-sensitive cell adhesion ligand.     

Multiple infundibulocystic basal cell carcinomas in association with human immunodeficiency virus

Infundibulocystic basal cell carcinoma (IBCC) is a relatively recently described variant of basal cell carcinoma that is controversial and not universally accepted. Excluding cases of nevoid basal cell carcinoma syndrome, IBCC usually presents as a small, solitary, superficial lesion on the face of older persons. There have been previous reports of diffusely distributed, multiple similar lesions, but there is disagreement about the diagnosis in these cases. We present a case of a 43-year-old man with multiple papular lesions which we believe represent IBCC in the setting of infection with the human immunodeficiency virus (HIV).     

Heterotransplantation of human basal cell carcinomas in "nude" mice.

Human basal cell carcinomas, obtained from 10 subjects were transplanted to 25 "nude" mice. Two methods of transplantation were used and compared. Grafting gave better results than subcutaneous implantation. Tumor cells were identified in 5 mice, however only 2 of them developed lesions with histology similar to human basal cell carcinoma. Grafts, in which tumors developed, were obtained from superficial basal cell carcinoma. No reasons for the cause of the low percentage of successful transplantation and slow rates of growth of the transplants are found; however, possible immunological, vascular and environmental factors are discussed.     

The relationship of basal cell carcinomas and squamous cell carcinomas to solar keratoses

Six thousand four hundred sixteen people aged 40 years and over from three different locations in Victoria (Australia) were examined on the hands, forearms, head, and neck for the presence of solar keratoses and basal (BCCs) and squamous cell carcinomas (SCCs). Analysis of the relationship between these tumors revealed that the factors which predicted the likelihood of developing a solar keratosis were essentially the same as those that predicted the likelihood of developing a BCC and/or an SCC. These were age, sex, years of residence in Australia, indoor or outdoor occupation, tanning ability, propensity to sunburn, and location of residence. The presence of a coexisting solar keratosis was necessary for the development of an SCC in contrast to the development of a BCC. The findings suggest that unlike BCCs, the majority of SCCs in light-exposed areas may arise from preexisting solar keratoses. Whereas the prevalence of BCCs and SCCs was relatively constant in the three locations, the prevalence of solar keratoses differed markedly in direct relation to the degree of isolation. This suggests that solar keratoses are a more sensitive indicator of sunlight exposure than invasive carcinoma.     

Treatment of basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome

Background  Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple basal cell carcinomas (BCCs). A major problem for these patients is the enormous amount of BCCs which can invade in the deep underlying structures, especially in the face. Different treatment modalities are used in these patients; surgical excision, Mohs micrographic surgery, cryotherapy, photodynamic therapy, ablative laser therapy and topical 5% imiquimod. There is no evidence based advice how to treat a NBCCS patient.
Objective  To give a review of the literature about the possible treatment modalities for the multiple BCCs in NBCCS patients.
Results  Literature consists mainly of case reports; no evidence based advice how to treat a NBCCS patient exists. Multiple treatments are available (surgical and non-surgical), and a lot of them can be combined. Treatment in a megasession is an option to diminish the medical and social inconvenience for the patient.

Conflicts of interest

None declared     

Determination of epidermal growth factor (EGF) receptors in basal cell carcinomas, squamous cell carcinomas and melanomas

We studied the binding of EGF receptors (EGF-R) in 19 basal cell carcinomas, 8 squamous cell carcinomas, and 9 malignant melanomas. Specific binding of EGF-R was detected in 10 of the basal cell carcinomas, and in all the 8 squamous cell carcinomas. None of the malignant melanomas showed EGF-R binding. A comparative study of the receptor status vs. clinical prognostic data, such as grading and clinical course, did not reveal any significant differences, whereas in ovarian carcinomas, the EGF receptor correlated with the prognosis.