桥粒芯糖蛋白1在不同表皮肿瘤中表达的研究

目的：了解桥粒芯糖蛋白1与表皮肿瘤的病理及生物学行为之间的关系。方法：采用过氧化物酶标记的链霉卵白素免疫组织化学染色方法，检测了桥粒芯糖蛋白1(Dsgl)在鳞状细胞癌、基底细胞癌、Bowen病、日光角化病、角化棘皮瘤、脂溢性角化病及正常皮肤中的表达。结果：Dsgl在正常表皮中显著表达；在鳞状细胞癌和基底细胞癌的肿瘤组织中表达显著减弱或消失；在Bowen病和日光角化病细胞间变区域无表达；在绝大多数角化棘皮瘤、脂溢性角化病中的表达为强而连续的胞膜染色，与正常表皮中的表达相似。结论：皮肤恶性肿瘤中Dsgl的表达显著减弱或消失，可能与肿瘤的侵袭性和转移有关，Dsgl可能对表皮良、恶性肿瘤的鉴别诊断具有一定价值。     

Neoplasms with sweat gland differentiation express various glycoproteins of the carcinoembryonic antigen (CEA) family

Carcinoembryonic antigen (CEA) is a well-established marker for sweat gland differentiation in adnexal neoplasms. In contrast to previous assumptions, CEA does not represent a single oncofetal antigen but comprises a family of homologous glycoproteins, i.e. the classical CEA-180, biliary glycoprotein (BGP), and non-specific crossreacting antigens (NCA). The aim of the study was to evaluate the distribution of the respective glycoproteins of the CEA family in sweat gland neoplasms, as compared to normal sweat glands. A panel of mono-specific antibodies was applied to a total of 83 samples of hyperplastic and cystic alterations of sweat glands, sweat gland neoplasms, and cutaneous metastases of different origin. Within a single group of neoplasms the immunohistochemical profile was rather consistent. Staining for both CEA-180 and NCA-90 indicated ductal differentiation of both eccrine and apocrine glands. Co-expression of CEA-180, NCA-90, and BGP was consistent with differentiation towards the secretory part of eccrine glands or the transitional portion of proximal ducts. Neoplasms with signs of apocrine secretion showed a preferential immunoreactivity for NCA-90 and BGP. In conclusion, a specification of the members of the CEA family may be of some value in the differential diagnosis of adnexal neoplasms, but not in the discrimination of sweat gland carcinoma from metastatic carcinoma.     

Cathepsin B and D expression in squamous cell carcinoma

To elucidate involvement ol protcinascs in malignancy of keratinocytes. expression ol catbepsin B, a cysteine proteinase. and catbepsin D. an aspartic proteinase. was ascertained in lormalin-lixed paraffin-embedded specimens of nortnal skin, squamous cell carcinoma (SCC). Bowen's disease, seborrboeic keratosis and basal cell carcinoma (BCC). Presence of procalbepsin B and an intermediate form of catbepsin D was coiilirmed by Westerti blolling and enzytne activity analysis. Cathepsin B stained more Intensely In SCC tumour cells tban in normal epidermis: staining patterns were diffuse, grantilar or botb. Diflusc and granular patterns (procatbcpsin B and mature enzyme, respectively) appeared in inner and outer parts of tumour islands, respectively. Five of 20 cases of Bowen's disease sbowed diffuse enhanced catbepsin B expression: 20 cases of seborrhoeic keratosis or BCC did not. Cathepsin D stained intensely in tumour cells of half the SCC cases. The staining manner and distribution of cathepsins B and D was similar in the cytoplasm of cancer cells. No enhanced staining of cathepsin I) was seen in any cases of Bowen's disease, seborrhoeic keratosis. or BCC. Coexistence and localization of active mature forms of cathepsins B and D suggests that cooperation between tbe two enzymes may play an important part in invasion of SCC.     

Hair cycle-dependent expression of a nonspecific cross reacting antigen (NCA)-50/90-like molecule on follicular keratinocytes

We found a carcinoembryonic antigen (CEA)-related antigen to be strongly expressed on a subset of follicular keratinocytes in normal human skin. The antigen was characterized immunohistochemically using a panel of antibodies against human CEA and CEA-related molecules. The expression of the antigen was studied in different phases of the hair cycle as well as in different hair types. Immunohistochemically, the antigen resembled the nonspecific crossreacting antigen (NCA)NCA-50/90 rather than true CEA. Its expression was limited to the innermost cells of the lowest segment of hair follicles in the catagen/telogen phases, being detected only where the hair shaft was attached to the epithelial hair sac in these phases. The same results were obtained for all hair types, i.e. terminal, vellus and intermediate hair. Coexpression of the antigen with both involucrin and differentiation-associated cytokeratins was noted in the cells in additional studies attempting to identify the exact subpopulations of follicular keratinocytes expressing the antigen in comparison with the expression of other functional markers. However, involucrin and the cytokeratins were also expressed in the upper segments of anagen as well as catagen/telogen hair follicles. Our findings strongly suggest that an NCA-50/90-like molecule is expressed cyclically on the innermost cells in the lowest segment of the outer root sheath only in catagen/telogen hair follicles. The cyclical expression in this specific subset of follicular keratinocytes only, in which the epithelial hair sac is attached to the hair shaft, may be associated with the stability of the attachment through the adhesive or, conversely, the repulsive function of CEA-related molecules, both of which have recently been proposed. Received: 16 January 1996     

Activation of fibroblast growth factor receptor 3 and oncogene-induced senescence in skin tumours

Background  The activation of oncogenes is an important step in tumorigenesis, and recently, oncogene-induced senescence (OIS) was proposed as a critical barrier against malignant transformation in normal primary cells.
Objectives  The aim of this study was to examine the activation of fibroblast growth factor receptor 3 (FGFR3) as an oncogene product and OIS in human skin tumours.
Methods  We investigated the activation of FGFR3 and OIS by mutation and immunohistochemical analysis in skin tumours, including seborrhoeic keratosis, actinic keratosis (AK), Bowen's disease (BD), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
Results  Activated point mutations of FGFR3 were identified in four of 22 cases (18%) of seborrhoeic keratosis, but no mutation was detected in the other skin tumours. Twenty-seven of 31 cases (87%) of seborrhoeic keratosis showed moderately to strongly positive expression of the FGFR3 protein, but almost all the other skin tumours were negative. On the other hand, almost all the seborrhoeic keratoses showed negative immunoreactivity for antiphoshohistone H2AX (γ-H2AX) as a marker of OIS, but 17 of 22 cases (77%) of AK were moderately to strongly positive. Immunoreactivity for γ-H2AX was significantly greater in AK than in seborrhoeic keratosis, BD, BCC and SCC.
Conclusions  The activation of FGFR3 might be a common feature in the tumorigenesis in seborrhoeic keratosis, although the activation does not induce a typical oncogenic signal in keratinocytes. In addition, OIS due to some oncogenic signals rather than activation of FGFR3 might be involved in the early skin carcinogenesis related to chronic ultraviolet radiation exposure.     

Carcinoembryonic antigen and related antigens expressed on keratinocytes in inflammatory dermatoses

Carcinoembryonic antigen (CEA) is recognized as being important not only as a tumour marker, but also as a cell adhesion molecule in the metastasis of malignant tumour cells, and in the development of inflammatory disorders in some organs. However, the role played by this antigen in inflammatory dermatoses has not been studied previously To investigate the expression of CEA in inflamed skin, we performed immunohistochemical studies to detect the antigen in both frozen and formalin-fixed, paraffin-embedded biopsy specimens of inflammatory dermatoses. using five different monoclonal antibodies and one polyclonal antibody against human CEA or CEA-related molecules CEA and CEA-related antigens were expressed by epidermal keratinocytes and by some infiltrating inflammatory cells in inflamed skin. The expression was observed primarily in the upper part of the malpighian layers of the epidermis. On the basis of the distribution of this expression, we suggest an additional role for CEA-related molecules, differing from their roles as tumour markers and adhesion molecules, namely that these molecules may be associated with the state of differentiation of epidermal keratinocytes Unexpected expression of CEA-related antigens was seen on normal follicular keratinocytes. Thus, it is conceivable that CEA-related antigen may also play a role in the biology of hair follicles.     

Cytokeratin expression in trichoblastic fibroma (small nodular type trichoblastoma), trichoepithelioma and basal cell carcinoma

Classical trichoblastic fibroma or small nodular type trichoblastoma (Ackerman) is a rare tumour. This tumour, trichoepithelioma and basal cell carcinoma (BCC) have some overlapping histopathological features. There are only a few reports on immunohistochemical studies in large series of these three neoplasms. We investigated immunostaining patterns of 10 different anticytokeratin (CK) antibodies and several other markers in these neoplasms, comparing them with the patterns in normal adult and fetal skin. In trichoblastic fibroma (three cases), CK1/5/10/14, CK7, CK8/18, CK10/11, CK14, CK17 and CK19 were expressed in the basaloid nests, and CK6 and involucrin were detected in the inner layers of keratinous cysts. Trichoepithelioma (seven cases) expressed CK1/5/10/14, CK8/18, CK14, CK17 and CK19 in the basaloid nests, and CK6, CK10, CK10/11 and involucrin were positive in the keratinous cysts. However, no CK7 expression was observed. Solid and keratotic types of BCC (29 cases) expressed CK1/5/10/14, CK7, CK8/18, CK14, CK17 and CK19 in the basaloid nests. The keratinous cysts in BCC were stained with anti-CK6, CK10, CK10/11 and involucrin antibodies. Coupled with the expression of CK8/18, CK17 and CK19 in the outer root sheath of the adult hair follicle, these three neoplasms shared a keratin phenotype characteristic of the outer root sheath. Judging from our immunohistochemical results, trichoblastic fibroma and BCC cannot be differentiated by their patterns of CK expression. The expression of CK7, which is noted in fetal hair follicles, trichoblastic fibroma and BCC, suggests the presence of subpopulations that retain fetal phenotypic characteristics in these two neoplasms. Although the current concept regards trichoepithelioma and trichoblastic fibroma as a single tumour group, the lack of CK7 expression in trichoepithelioma supports the notion that the two are different.     

Expression of OKM5 antigen on keratinocytes in some dermatoses.

Employing an avidin-biotin complex immunoperoxidase technique, it was found that there was OKM5 but no OKM1 antigen expression on the keratinocytes of the upper epidermis from all the studied specimens of seborrheic keratosis, verrucous nevus, Bowen's disease, BCC, SCC, MM, lichen planus, psoriasis vulgaris, condyloma acuminatum, and sporotrichosis as well as in two of eight cases of nevus pigmentosus. Our findings indicate that OKM5 antigen expression on epidermal keratinocytes is usually associated with dermal infiltration. It is assumed that human keratinocytes in cutaneous lesions, like the OKM1- OKM5+ monocyte/macrophage lineages, might play certain roles in immune responses and possibly function as antigen-presenting cells.     

Expression of E-cadherin in human epidermal non-melanoma cutaneous tumours

Summary E-cadherin is a calcium-sensitive, cell-to-cell, adhesion molecule that is expressed widely in normal human epithelial tissue. Abnormal expression has been described in colorectal, breast and nasopharyngeal squamous cell carcinomas, where loss of E-cadherin is associated with an increased metastatic potential. We have examined, by standard immunohistochemical techniques using the monoclonal antibody HECD-1 (E-cadherin monoclonal antibody), the distribution of E-cadherin in normal human skin and in non-melanoma neoplastic lesions. In the normal epidermis, E-cadherin was strongly expressed on the surface of keratinocytes and specialized epithelial structures. Staining was absent from the lower pole of basal keratinocytes in contact with the basement membrane. Weak cytoplasmic staining was also noted in basal keratinocytes. No reactivity was demonstrated in dermal structures. The assessment of cutaneous tumours demonstrated an altered pattern of staining in most cases. Cell surface expression was reduced in 28 of 30 cases of basal cell carcinomas (BCC). Twenty showed an additional feature of positive staining on the dermal aspect of peripheral cells of tumour lobules. In squamous cell carcinomas (SCC) ( n = 16), surface expression was attenuated in eight and absent in a further four. Strong surface expression, similar to normal skin was seen in all examples of Bowen's disease ( n = 6), viral wart ( n = 3), seborrhoeic keratosis ( n = 3) and actinic keratosis ( n = 4). This study demonstrates that, in BCC and SCC, but not in premalignant lesions, cell-surface expression of E-cadherin is reduced, consistent with the observation that the loss of E-cadherin is associated with tumour invasion.     

Significance of PC cell-derived growth factor and cyclin D1 expression in cutaneous squamous cell carcinoma

Background. PC cell‐derived growth factor (PCDGF) is an autocrine growth factor originally purified from the highly tumorigenic teratoma PC cell line. It participates in tumorigenesis and tumour progression through upregulation of cyclin D1. To date, there has been no report on the role of PCDGF in skin cancer, to our knowledge. Aim. To investigate the expression of PCDGF and cyclin D1 in basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and seborrhoeic keratosis (SK), and their relationship with the clinicopathological parameters of SCC. Methods. Immunohistochemical expression of PCDGF and cyclin D1 was examined in 42 SCC, 30 BCC and 20 SK tissues. Results. PCDGF and cyclin D1 were overexpressed in SCC or BCC tissues compared with normal skin or SK, and their expressions were significantly higher in SCC than in BCC. Moreover, positive expression of PCDGF and cyclin D1 was significantly correlated with depth of invasion and metastasis of SCC. There was significant correlation between PCDGF and cyclin D1 expression in SCC. Conclusions. Expression of PCDGF and cyclin D1 plays an important role in the tumorigenesis of BCC and SCC. Abnormal expression of PCDGF and Cyclin D1 may be related to invasion and metastasis of SCC.     

Expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67 in benign, premalignant and malignant skin lesions with implicated HPV involvement.

A series of 120 biopsies from benign (verruca vulgaris and keratoacanthoma), premalignant (actinic keratosis and extragenital Bowen's disease) and malignant (squamous cell carcinoma) skin lesions were studied immunohistochemically for the expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67. The presence of human papillomavirus (HPV) DNA in these samples had been analysed previously using in situ hybridization (ISH) and PCR. Moderate to intense expression of both PCNA and Ki-67 was present in most of the lesions studied. PCNA staining was extensive in the epidermis underneath the layers where abundant HPV DNA staining was shown in HPV DNA-positive verrucas. In keratoacanthomas, p21 and PCNA expression remained low, despite intense p53 expression. In actinic keratosis, only half of the specimens showed overexpression of p53 associated with moderate or intense expression of PCNA. In extragenital Bowen's lesions, all these cell-cycle markers were overexpressed, but in squamous cell carcinomas, they were heterogeneously expressed and showed no correlation with tumour differentiation. Our results suggest a mechanism by which HPV can reactivate the host genes (leading to cell proliferation) to support its own DNA replication. Also p21 might start keratinocyte differentiation in areas where HPV DNA replication starts. Cell proliferation remained active in actinic keratosis and Bowen's lesions, emphasizing the precancer character of these lesions in contrast with the benign nature of keratoacanthoma and verruca vulgaris.     

Functional thrombomodulin expression on epithelial skin tumours as a differentiation marker for suprabasal keratinocytes

Summary In normal human skin, immtmoreactive thrombomodulin (TM) is expressed in a strict differentiation related pattern. solely in suprabasal spinous layer keratinocytes. To evaluate the polential application of TM as a differentiation marker for keratinocyte-derived skin tumours, we have studied immunohistopathological, biochemical and functional TM activities in various skin tumours. Immunoreactive, full sized and enzymatically active TM was expressed in keratinocyte-derived skin tumours (squamous cell carcinoma, seborrhoeic keratosis and partly Bowen's disease), as well as normal epidermal keratinoeytes and endothelial cells. However, no TM was detected in basal cell carcinotnas, senile keratosis or non-squanious epithelial tumours such as malignant melanoma, naevus pigmentosus and Paget's disease. Interestingly, decreased expression was observed in verruca vulgaris. These findings suggested that differentiation-dependent TM expression was restricted to epithelial skin tumours and undetectable on neural crest derived tumours. TM is a differentiation marker for spinous layer keratinocytes and is a useful tool in histopathological study of epithelial tumours.     

Ber EP4与EMA染色在皮肤基底细胞上皮瘤和鳞状细胞癌诊断中的意义

目的 观察BerEP4和EMA染色在皮肤基底细胞上皮瘤和鳞状细胞癌诊断中的意义.方法 用免疫组化SP法检测BerEP4和EMA在皮肤基底细胞上皮瘤、鳞状细胞癌、光线性角化病、Bowen病、脂溢性角化病、寻常疣和基底鳞状细胞癌皮损肿瘤成分及周围组织、皮肤附属腺体中的表达.结果 所有基底细胞上皮瘤和基底鳞状细胞癌肿瘤细胞呈BerEP4阳性,而鳞状细胞癌、光线性角化病、Bowen病、脂溢性角化病和寻常疣呈BerEP4阴性;多数鳞状细胞癌、Bowen病和部分光线性角化病肿瘤细胞及病变区域呈EMA阳性,而基底细胞上皮瘤、基底鳞状细胞癌、脂溢性角化病和寻常疣呈EMA阴性.结论 联合使用BerEP4和EMA能很好地协助诊断皮肤基底细胞上皮瘤、基底鳞状细胞癌、癌前病变及一些良性增生性皮肤病.     

Expression of lamins depends on epidermal differentiation and transformation

BACKGROUND: It has been suggested that A- and B-type lamins, proteins of the nuclear lamina, play important roles in the morphogenesis of the nucleus and cellular differentiation. OBJECTIVE: To investigate the expression of these nuclear proteins in normal skin and some keratinocytic tumours of the skin. METHODS: We examined by means of immunohistochemistry the expression of lamins in normal skin and some keratinocytic tumours of the skin, such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease, solar keratosis, keratoacanthoma and seborrhoeic keratosis. RESULTS: In normal skin, A-type lamin was expressed in all epidermal cells, but the expression level of B-type lamins diminished from basal cells to granular cells. In keratinocytic tumours, the expression of A-type lamin was reduced, especially in BCCs, Bowen's disease and poorly differentiated SCCs. B-type lamins were reduced and exhibited heterogeneous expression patterns in most well-differentiated SCCs and keratoacanthomas. Antibodies against B-type lamins stained only peripheral cells of the lobules in keratoacanthomas, while no regular staining patterns were seen in well-differentiated SCCs. CONCLUSIONS: Lamin expression depends on the differentiation and transformation of the human skin. This finding should be useful for the diagnosis of keratinocytic tumours.     

环氧化酶-2在表皮肿瘤中的表达

目的 探讨环氧化酶-2在不同表皮肿瘤中的表达及意义。方法 选择鳞状细胞癌8例、基底细胞上皮瘤10例、Bowen病8例和脂溢性角化病12例,运用免疫组化方法观察肿瘤细胞中环氧化酶-2的表达。结果 与正常表皮相比,环氧化酶-2在鳞状细胞癌、Bowen病、基底细胞上皮瘤中的表达明显上调,尤其以鳞状细胞癌中的表达最强。而环氧化酶-2在脂溢性角化病中的表达与正常人皮肤的表达近似。结论 环氧化酶-2表达的上调可能在表皮肿瘤的发生发展中发挥一定作用。     

Altered distribution of 1-2B7B antigen in basal cell carcinoma, squamous cell carcinoma and Bowen's disease.

Skin lesions of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Bowen's disease were immunohistochemically examined using the 1-2B7B monoclonal antibody, which recognizes a 120 kDa polypeptide component found in hemidesmosomes of normal human epidermis and hemidesmosome-like adhesion junction of vascular endothelial cells, to disclose altered characteristics of the interface between the tumor cell aggregate and stromal tissues of the epidermal neoplasms. In BCC, 1-2B7B antigen was rarely expressed at the tumor cell aggregate-stromal tissue interface, where poorly developed hemidesmosometonofibril complexes and a normal-looking lamina densa were detectable. In SCC and Bowen's disease, 1-2B7B antigen was expressed not only along the interface of the tumor nest and stromal tissue, but also in the intercellular space of the desmosomes and other adhesion junction structures that lack associating tonofibrils. In the invading front of SCC, 1-2B7B antigen had partly disappeared from the tumor cell aggregate-stromal tissue interface, where neither hemidesmosomes nor lamina densa were noted. The altered distribution of this hemidesmosomal component in the epidermal neoplasms seems to reflect aberrant interaction of neoplasmic cells and surrounding stromal tissue.     

GLUT-1、Ki-67在皮肤肿瘤中的表达及意义

目的：探讨葡萄糖转运蛋白-1（GLUT-1）在脂溢性角化病（SK）、日光性角化病（AK）、Bowen病（BD）、鳞状细胞癌（SCC）中的表达及其与细胞增殖因子Ki-67之间的关系。方法：采用免疫组化法检测了95例不同皮肤肿瘤GLUT-1及Ki-67的表达。结果：GLUT-1及Ki-67在SK及正常皮肤都不表达,在AK、BD及SCC表达上调,并且二者的阳性表达强度间具有正相关性。结论：GLUT-1在恶性皮肤肿瘤中表达上调,与肿瘤的侵袭和转移有关。其表达强度可作为判断皮肤肿瘤恶性程度的检测指标,对诊断及鉴别诊断具有参考价值。     

E-钙粘着蛋白在不同表皮肿瘤中的表达及意义

目的　探讨E 钙粘着蛋白 (E cad)在鳞状细胞癌 (SCC)、基底细胞癌 (BCC)、Bowen病、日光角化病 (AK)、角化棘皮瘤 (KA)、脂溢性角化病 (SK)中的表达与肿瘤分化程度、侵袭转移等生物学行为的关系。方法　用免疫组化染色方法检测 12 9例不同表皮肿瘤E cad的表达。结果　E cad在BCC ,SK ,KA表皮中的表达与正常表皮相似 ,为表皮全层细胞间较强的染色 ,而在SCC中表达显著减弱或完全无表达 ,在AK和Bowen病表皮正常区域表达正常或下调 ,但在细胞间变区域无染色。结论　E cad在恶性皮肤癌中表达下调 ,可能与表皮肿瘤的侵袭和转移有关。     

Expression of trichohyalin in dermatological disorders: a comparative study with involucrin and filaggrin by immunohistochemical staining

To investigate the function of trichohyalin during terminal differentiation of the skin, immunohistochemical studies were performed on trichohyalin and its related proteins, filaggrin and involucrin, the components of the cornified cell envelope. In skin disorders unrelated to tumours, weak trichohyalin expression was found in a few granular cells or in the horny layer of psoriasis, ichthyosis, keratosis pilaris, porokeratosis, chronic dermatitis and callus. Similar trichohyalin expression was found in epidermal tumours, such as seborrheic keratosis, actinic keratosis, Bowen's disease and well-differentiated squamous cell carcinoma. In follicular tumours, trichohyalin expression was positive in trichoepithelioma, keratotic basal cell epithelioma, proliferating trichilemmal tumour, trichilemmoma, pilomatricoma and keratoacanthoma. From comparative studies with filaggrin and involucrin, trichohyalin expression was co-localized with them in molluscum contagiosum, keratoacanthoma and pilomatricoma. From this study, trichohyalin is revealed to have close functional relationship with other markers of terminal differentiation as a precursor of the cornified cell envelope of the skin.     

CD44在某些皮肤肿瘤中表达的初步研究

目的：探讨CD44在皮肤肿瘤中的表达情况。方法：免疫组化法。结果：在鳞癌和基癌中,癌巢距表皮越近,CD44的表达越强;反之,CD44的表达越弱。在痣细胞痣和恶性黑素瘤（恶黑）标本中,CD44标准型（CD44S）均表达。在其它皮肤肿瘤中,CD44的表达同正常皮肤。结论：在鳞癌和基癌中,CD44的表达与癌巢距表皮的远近有关。CD44S的表达与痣细胞的良性或恶性无关。