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.     

Pachydermoperiostosis with cutaneous squamous cell carcinomas

A 46-year-old man visited our department with masses on the face and a skin problem. Approximately 15 years ago, he had noticed marked thickening of the skin on the face and scalp, which had exaggerated progressively to produce deep wrinklings with seborrhea ( Fig. 1 ). He had profuse perspiration of the face, hands, feet, and the upper aspects of the trunk.

Figure 1 Open in figure viewer PowerPoint Clinical features of pachydermoperiostosis, consisting of thickened skin folds and deep wrinkles on the forehead and scalp. A large ulcerative tumor on the nasal dorsum and a nodular one on the glabellar area (arrow) can be seen.     

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.     

Complete response of advanced cutaneous squamous cell and basal cell carcinomas with sequential cemiplimab and sonidegib therapy

A 78-year-old woman was referred to our skin cancer centre with three previous incomplete resections in the left cavum conchae of a deep-infiltrating locally advanced, but still asymptomatic basal cell carcinoma (BCC). The patient noted furthermore two rapidly growing exophytic lesions in the left preauricular and cervical area in the last weeks. The clinical and histological distinction of locally advanced from metastatic cutaneous squamous cell carcinoma (CSCC) lesions was challenging. Imaging analysis with CT scans showed, however, an involvement of the parotid gland as well as multiple small lymph node metastases. The interdisciplinary tumour board decision at our institution recommended a systemic treatment with the PD1-antibody cemiplimab. After 13 cycles with cemiplimab at a dose of 350 mg intravenously every 3-weeks, the patient showed a complete response of the two CSCC lesions with histological confirmation. However, the BCC of the left ear appeared to be unchanged and still asymptomatic. The interdisciplinary tumour board considered this tumour to be no candidate for a curative resection or irradiation. Therefore, the patient was exposed to the hedgehog inhibitor sonidegib with a conventional dose of 200 mg orally per day. After 3 months of treatment, the tumour showed a markable regression and a complete response was confirmed by 3-punch biopsies from this preoperated lesion. Both cemiplimab and sonidegib were excellently tolerated with almost no adverse events apart from a mild fatigue (CTC grade 1) over the first 3 weeks of the cemiplimab therapy. There were no laboratory abnormalities found.     

Cytodiagnosis of cutaneous basal and squamous cell carcinoma

OBJECTIVE: We performed a prospective study to evaluate the diagnostic accuracy of cytologic examination in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), in order to assess its clinical value. Study design Samples were taken by the "scraping" technique which involves scraping with a scalpel blade directly over the skin tumor surface, smearing the cells onto several glass slides, and fixing them with "citospray." The specimens were stained with the Papanicolaou stain. Punch biopsies were taken to confirm the clinical and cytologic impression. RESULTS: We collected 45 skin tumors in total, clinically presumed to be either BCC (n = 15) or SCC (n = 30). Imprint cytology demonstrated to be of help in the rapid diagnosis of skin tumors. CONCLUSIONS: Cytologic examination is easy to perform, saves time, provides a rapid diagnosis, and can be considered, under experienced hands, reliable in the confirmation of malignant skin tumors. Cytology does not give much information about tumor patterns or subtypes which can be related to aggressive behavior and can be very important in further therapeutic decisions. Therefore, histopathologic confirmation is mandatory before any therapeutic maneuver.     

皮肤鳞状细胞癌和基底细胞癌组织中β-转化生长因子1及受体1表达

目的:观察皮肤鳞状细胞癌(SCC)和基底细胞癌(BCC)组织中β-转化生长因子1(TGF-β1)及其受体1(TβR-Ⅰ)表达与临床、组织病理特征的关系。方法:应用ABC免疫组化技术检测48例皮肤SCC和41例BCC手术切除标本中TGF-β1和TβR-Ⅰ的表达。结果:SCC中TGF-β1、TβR-Ⅰ表达明显高于BCC(P<0.05);高分化SCC中TβR-Ⅰ表达明显上调(P<0.05),但TGF-β1表达与肿瘤分化程度无关(P>0.05)。SCC和BCC中TGF-β1与TβR-Ⅰ的表达呈显著正相关(r=0.739,P<0.001;r=0.716,P<0.001),但其与患者性别、年龄、病程、发病部位、病灶、淋巴结转移及BCC侵袭性无关(P>0.05)。结论:TGF-β1表达与肿瘤分化程度、侵袭性及淋巴结转移无关。     

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.     

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.     

Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50-80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known. OBJECTIVES: To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease. METHODS: Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1. RESULTS: Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours. CONCLUSIONS: The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.     

LC3A-positive "stone-like" structures in cutaneous squamous cell carcinomas

This study was set to investigate the relation between autophagic activity and the aggressiveness of cutaneous squamous cell carcinomas (SCC), as indicated by tumor thickness and proliferative activity. The anti-LC3A antibody, recognizing both the soluble and the autophagosome-bound forms of the protein, and a standard immunohistochemical technique were applied to 75 cutaneous SCC of variable tumor thickness. The study was complemented by staining for MIB1. Three patterns of LC3A reactivity were recognized: diffuse cytoplasmic, cytoplasmic/perinuclear, and "stone-like" structures (SLS), that is, large, rounded, densely stained amorphous material, 5 μm on average, enclosed within cytoplasmic vacuoles. Higher numbers of SLS were counted in >6-mm-thick SCC compared with the intermediate-thickness tumors (2.1-6 mm) and the <2-mm-thick tumors; the mean recorded values, being 8.8, 4.55, and 1.55, respectively, were statistically significant. The diffuse cytoplasmic staining showed a nearly inverse trend, whereas the perinuclear pattern, expressed in <10% of the total, was not evaluated. With regard to MIB1 proliferation index, this increased with tumor thickness and, in linear regression analysis, was directly linked with SLS counts and inversely with the cytoplasmic pattern. These data suggest that autophagic activity in SCC, when expressed as high LC3A/SLS counts, can be regarded as an indicator of tumor aggressiveness.     

Fas/FasL在基底细胞癌和鳞状细胞癌中的表达

目的:检测Fas/FasL在基底细胞癌(BCC)和鳞状细胞癌(SCC)中的表达.方法:采用SABC技术分别检测Fas/FasL在BCC、SCC及正常人对照皮肤中的表达.结果:Fas/FasL在BCC组不表达或弱表达,较正常人组无显著差异(P＞0.05);SCC组Fas和FasL的表达均高于对照皮肤(P＜0.05和＜0.01).Fasl染色主要集中于肿瘤细胞,弥漫染色,在肿瘤团块边缘表达更强;Fas在角珠处表达较强.结论:FasL在基底细胞癌不表达或弱表达,表明BCC侵袭扩散能力低,而在鳞状细胞癌中高表达可能与肿瘤的侵袭扩散能力高有关.     

PGP 9.5 expression in cutaneous keratoacanthomas and squamous cell carcinomas

The aim of the study was to investigate the expression of PGP 9.5 in cutaneous keratoacanthomas (KAs) and squamous cell carcinomas (SCCs). Thirty-one cases of KA (10 in the growth stage, 9 in the mature phase and 12 in the involution stage) and 36 SCCs including 13 well differentiated cases, 12 moderately differentiated tumors, 7 poorly differentiated lesions and 4 pseudoadenoid entities were investigated. PGP 9.5 expression was positively correlated with tumor stage (P < 0.001) and potential perineural invasion (P < 0.001). There was no significant difference in the distribution of patients presenting variable levels of PGP 9.5 staining with regard to maximal tumor size and the extent and degree of stromal invasion. PGP 9.5 expression proved closely associated with tumor aggressiveness and is classified as a marker for predicting the outcome of resection-treated skin cancer patients.     

Concurrent basal cell and squamous cell carcinomas associated with hydroxyurea therapy

We report a case of a 76-year-old woman with concurrent onset of two primary cutaneous malignancies, one at the fourth finger and another at the dorsum of the same hand. The patient was on long-term therapy with hydroxyurea (HU) for polycythemia vera. Histopathologic and immunohistochemical studies revealed two different malignant cutaneous lesions, i.e. basal cell carcinoma (positive for bcl-2 and negative for vimentin, EMA and CK5/6) and poorly differentiated sarcomatoid squamous cell carcinoma (positive for vimentin, EMA and cytokeratins CK5/6, and negative for bcl-2). In addition, p53 was positive in approximately 50% of squamous cell carcinoma cells and in almost all basal cell carcinoma cells. The presence of low-risk human papillomavirus (HPV, types 6, 11) was verified by polymerase chain reaction, but only in the surrounding normal skin tissue, whereas HPV infection could not be detected in either carcinoma. In this patient, concurrence of two different skin carcinomas on sun-exposed skin, in the absence of HPV, suggest direct involvement of potentially mutagenic HU therapy, through influence on DNA synthesis and repair mechanisms, in conjunction with ultraviolet exposure. Therefore, we suggest that in patients on HU therapy with cutaneous side effects, referral to a dermatologist should be obligatory.     

Analysis of the vitamin D system in cutaneous squamous cell carcinomas

BACKGROUND: Increasing evidence points at an important function of vitamin D metabolites for growth regulation in various tissues, and new vitamin D analogs are interesting candidates for the treatment of malignancies, including squamous cell carcinomas (SCC). METHODS: We have analyzed expression of vitamin D receptor (VDR), vitamin D-25-hydroxylase (25-OHase), 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-OHase), and 1,25-dihydroxyvitamin D-24-hydroxylase (24-OHase) in SCC. RESULTS: Intensity of VDR immunoreactivity was increased in SCCs as compared to normal human skin. VDR staining did not correlate with histological type or grading, nor with markers for proliferation, differentiation, or apoptotic cells. Incubation of SCC cell lines (SCL-1, SCL-2) with calcitriol resulted in a dose-dependent suppression of cell proliferation (approximately up to 30%) in vitro, as measured by a tetrazolium salt (WST-1)-based colorimetric assay. RNA levels for VDR, 25-OHase, 1 alpha-OHase, and 24-OHase were significantly elevated in SCCs as compared to HS, as measured by real-time polymerase chain reaction. CONCLUSIONS: Our findings demonstrate that modulation of VDR expression and local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation of SCCs. Additionally, SCCs represent potential targets for therapy with new vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of calcitriol synthesis/metabolism in these tumors.     

Caspase-3在皮肤鳞状细胞癌及光线性角化病中的表达

目的：检测Caspase-3在皮肤鳞状细胞癌及光线性角化病组织中的表达。方法： 应用免疫组化法检测16例皮肤鳞状细胞癌皮损、27例光线性角化病皮损及24例正常皮肤组织中Caspase-3蛋白的表达。结果：Caspase-3在皮肤鳞状细胞癌、光线性角化病及正常皮肤组织的表达率分别为37.50%,51.85%,79.17%,其表达含量在皮肤鳞状细胞癌、光线性角化病、正常皮肤组织逐渐增加。结论：Caspase-3蛋白表达下调可能参与皮肤鳞状细胞癌及光线性角化病的发病过程。