外阴白斑细胞角蛋白的表达的意义探讨

采用多克隆ＲＫ１抗体和单克隆Ｋ２７抗体，应用免疫组织化学ＡＢＣ法，观察了７４例女阴白的在不同病变的表达方式，研究结果表明，Ｋ２７可作为角化或正在角化细胞的标志物，应用Ｋ２７单克隆抗体，外阴白斑ＣＫ异常均发生在疾病不同类型的细胞增殖状态，提示角蛋白表达的改变可能与引起角阮细胞的高度增生因素有关。用Ｋ２７单克隆抗体，有助于增生病变与萎缩病变及良性与恶性病变的区别。     

光线性角化病皮损的细胞DNA含量流式细胞分析

光线性角化病的病理组织学特征为不同程度的表皮细胞的非典型增生。为了更加客观地反映该病的这一特征，应用流式细胞技术定量分析了２７例光线性角化病皮损细胞的ＤＮＡ含量及细胞增殖活性。结果：光线性角化病细胞的增殖指数（ＰＩ）同于正常人皮肤的ＰＩ值（Ｐ〈０．０５），８例非典型增生严重的光线性角化病细胞的ＤＮＡ指数（ＤＩ）高于其余１９例光线性角化病的ＤＩ值（Ｐ〈０．０５）。提示：光线性角化病皮损细胞增殖活跃，     

光线性角化病皮损细胞Bcl—2基因表达产物的定量分析

Ｂｃｌ－２蛋白是Ｂｃｌ－２基因的表达产物，可抑制细胞凋亡，在某些恶性肿瘤细胞出现过度表达。为探讨Ｂｃｌ－２蛋白与光线性角化病（ＡＫ）的关系，作者用流式细胞免疫荧光技术，检测了２７例ＡＫ。结果显示：２７例ＡＫ及正常对照的Ｂｃｌ－２蛋白相对含量ＦＩ（ＦｌｕｏｒｅｓｃｅｎｃｅＩｎｄｅｘ）分别为１．１５０±０．１８８和０．９９６±０．０６５（Ｘ－±Ｓ），０．０５＜Ｐ＜０．０１。但其中８例不典型增生严重ＡＫ的ＦＩ为１．３３５±０．０１７６（Ｘ－±Ｓ），与正常对照相比Ｐ＜０．０２。提示该病的Ｂｃｌ－２蛋白有增高的倾向。     

角化棘皮瘤25例临床病理分析

角化棘皮瘤２５例临床病理分析王万惠，乐德凤江苏省海安皮肤病医院病理科（邮政编码２２６６００）角化棘皮瘤（Ｋｅｒａｔｏａｃａｎｔｈｍａ，ＫＡ）为一种可以自愈的皮肤表皮肿瘤，因其生长较快，上皮往往增生活跃，以致临床和病理上与鳞状细胞癌（Ｓｑｕａｍｏｕｓ－...     

角化棘皮瘤与鳞状细胞癌患者表皮细胞凋亡和增殖的研究

目的 探讨角化棘皮瘤与皮肤鳞状细胞癌患者表皮细胞凋亡和增殖的差异。方法 采用末端特异性ＤＮＡ标记技术和免疫组化法，原位检测了２０例角化棘皮瘤和２５例鳞状细胞癌患者表皮的细胞凋亡、凋亡相关基因ｂａｘ及ｂｃｌ－２和代表细胞增殖的核抗原Ｋｉ－６７的表达。结果 角化棘皮瘤的细胞凋亡率（４８．８３％）明显高于鳞状细胞癌（２６．０８％），前者的增殖率（９．０３％）明显低于后者（２７．２０％）。鳞状细胞癌分化程     

口腔粘膜白斑的现代研究和概念

口腔粘膜白斑的最主要问题是镜检细胞有无不典型增生.不典型增生提示恶变可能.无不典型增生的损害很少发展成不典型增生,称为良性型.其特点是角化过度及慢性炎症细胞浸润.每个口腔粘膜白斑病例都必须活检,如有不典型增生,则应视为癌前期病变而切除.如无,则可视为良性,去除吸烟或牙病所致的刺激后病变可消退.良性型很少发展成不典型增生,通常无须手术.良性型是对吸烟或其它刺激的反应性角化过度.不典型增生型可能向恶性转化,通常消除刺激后并不消退,治疗为手术切除,停止吸烟,矫正其它刺激因素.广泛的粘膜白斑必须多处活检以确定有无不典型增生.严重的不典型增生实际上就是原位癌.临床上约15～20%的粘膜白斑发生不典型增生.     

皮肤附属器肿瘤的免疫组化研究

为探讨免疫组化技术对附属器肿瘤的诊断价值，作者利用ＰＡＰ方法，以ＣＥＡ、ＥＭＡ、Ｓ－１００蛋白、角蛋白Ｋ１７４及Ｋ２７的单克隆抗体对２４例皮肤附属器良性瘤进行了染色。结果显示，汁腺肿瘤对ＣＥＡ、ＥＭＡ及角蛋白Ｋ１７４呈阳性反应，毛源性肿瘤仅对角蛋白Ｋ１７４及Ｋ２７阳性。皮脂腺肿瘤则对ＥＭＡ及角蛋白Ｋ１７４及Ｋ２７阳性。并提示，几种抗体联合应用较单一一种抗体能更有效地鉴别皮肤附属器及其它源性的肿瘤。     

地方性慢性砷中毒皮损内郎格罕细胞的研究

采用单克隆抗体Ｌｅｕ６间接免疫酶标法对新疆车排子地区地方性慢性砷中毒（ＥＣＡ）２５例３０份皮损内郎格罕细胞（ＬＣ）进行研究，发现２５份非肿瘤性角化症病变区表皮的角质层增厚，表皮内ＬＣ数增加，３份色素异常性皮损的表皮色素颗粒减少或消失区内ＬＣ数较多。２份恶性角化症，且份为鲍温病，其病变区内ＬＣ数目较多，而另１份鳞癌的癌巢中未见ＬＣ。认为砷角化症及色素异常的发生、发展及皮肤癌变的可能与皮肤ＬＣ有着密切的关系。     

鳞癌与脂溢性角化癌DNA倍体图像定量分析

目的 对脂溢性角化病（ＳＫ）及侵袭性癌进行ＤＮＡ定量分析，以回顾性探讨两者之间的关系。方法 应用ＨＩ－ＣＩ真彩色病理图像分析仪对９例ＳＫ，１６例鳞癌（ＳＣＣ０进行ＤＮＡ倍体图像分析。结果 ＳＣＣ多呈现Ｃ５，〉Ｃ５，ＳＫ多呈现Ｃ３－４，但１例ＳＫ组织病理示增生活跃，ＤＮＡ倍体分析出现少量的〉Ｃ５细胞，与ＳＣＣ比较差异显著，提示部分染色已发生了质变，有癌变潜在可能。结论 如临床上遇到ＳＫ有增大趋势，     

倒置性毛囊角化病10例临床和病理分析

对10例（男6例,女4例）经病理证实的倒置性毛囊角化病患者进行回顾性分析。结果示患者的平均年龄为31~76岁,平均48.6岁。9例患者无症状。6例患者的病变发生于面部。10例患者皮损均表现为单发的丘疹（5例,50%）或结节（5例,50%）,临床上很难与其他角化性病变以及恶性肿瘤相鉴别。本组病变组织均有不同程度的角化过度和角化不全,表皮均有向内增生和鳞状涡。     

粘膜白斑损害中HPV DNA的检测及细胞周期相关因子的表达

目的　探讨人乳头瘤病毒 (HPV)感染和细胞周期相关因子周期素E(cyclinE)及周期素依赖性蛋白激酶抑制蛋白p2 7在外生殖器粘膜白斑损害发病中的作用。方法　采用通用型引物PCR方法对 3 2例外生殖器粘膜白斑损害进行粘膜型HPVDNA的检测 ,并应用SP免疫组化方法检测病变中cyclinE和p2 7表达。结果　 3 2例粘膜白斑损害中粘膜型HPVDNA全部阴性 ;粘膜白斑损害cyclinE表达阳性率及阳性强度均高于正常对照 ,且有统计学差异 (P <0 .0 5) ;而p2 7表达阳性率及阳性强度均低于正常对照 ,但无统计学差异 (P >0 .0 5) ,粘膜白斑损害中cyclinE和p2 7的表达有显著相关性。结论　外生殖器粘膜白斑损害的发生可能与HPV感染关系不大 ;细胞周期相关因子cyclinE和p2 7表达改变及二者的相互作用可能在外生殖器粘膜白斑损害的发生及癌变中起重要作用     

Heat shock proteins (HSP70 and HSP27) as markers of epithelial dysplasia in oral leukoplakia

Heat shock proteins (HSPs) play a significant role in cell proliferation, differentiation, and oncogenesis. HSP70 and HSP27 are constitutively and gradually expressed in a broad range of normal tissues and neoplasms, and their expression has been assessed as markers for oral epithelial dysplasia. The study involved 43 patients with oral leukoplakia (OL): 23 were categorized as nondysplastic and 20 as dysplastic OLs. Immunohistochemistry was carried out with the monoclonal antibodies HSP70 and HSP27. The presence of epithelial dysplasia and its histologic grading was evaluated according to the World Health Organization classification: mild, moderate, and severe squamous epithelial dysplasia. Expression of HSPs within the epithelium was also evaluated. The difference in the percentage of HSP70 positive nuclei in nondysplastic and dysplastic OL reached statistical significance(Equation is included in full-text article.)95% confidence interval = 17.74-43.82; P = 0.000). None of the 43 specimens analyzed showed positive nuclear immunostaining for anti-HSP27 antibody. No significant difference for HSP27 cytoplasmic expression could be identified between OL with or without epithelial dysplasia(Equation is included in full-text article.)95% confidence interval = 0.44-3.95; P = 0.89). It is concluded that the nuclear HSP70 immunoexpression could be an objective marker for the presence of the epithelial dysplasia in OL.     

Immunologic characteristics of keratins in extramammary Paget's disease

Six cases of extramammary Paget's disease were immunohistochemically investigated with several antikeratin monoclonal antibodies. Paget cells and surrounding epidermal keratinocytes were equally stained with an antikeratin monoclonal antibody, HKN-4, which recognizes a broad spectrum of keratins. However, Paget cells were clearly distinguished from the surrounding epidermal keratinocytes by HKN-2, which does not react with keratins of secretory cells but does react with keratins of ductal and myoepithelial cells of sweat glands and with epidermis and hair tissue of the normal skin. The HKN-2 did not bind to Paget cells, but the surrounding keratinocytes were positive. CK7, LE41, RGE53, and LP2K, which recognize simple epithelium-type keratins 7 (molecular weight [MW], 54,000; type II), 8 (MW, 52,500; type II), 18 (MW, 45,000; type I), and 19 (MW, 40,000; type I), respectively, stained Paget cells but not the surrounding keratinocytes. Two cases of Merkel cell carcinoma, examined as controls, showed positivity to LE41 and RGE53 but not to CK7 and LP2K. Since in the normal skin the secretory cells of sweat glands showed the same keratin expression as that of Paget cells, Paget cells of extramammary Paget's disease may be derived from or differentiate to the secretory cells of sweat glands.     

Immunolabeling pattern of cytokeratin 19 expression may distinguish sebaceous tumors from basal cell carcinomas

Background:  Distinction between sebaceous tumors and basal cell carcinomas can often pose diagnostic problems. Recent work with the antibody to cytokeratin 19 (CK 19) has shown that this marker has high specificity for undifferentiated basaloid cells. Our aim was to evaluate the use of CK 19 staining patterns in differentiating between sebaceous tumors and basal cell carcinomas. The sebaceous tumors that were examined in this study included sebaceous adenomas, sebaceous epitheliomas (sebaceomas) and sebaceous carcinomas.
Methods:  Thirty-seven cases including 5 sebaceous adenomas, 16 sebaceous epitheliomas, 6 sebaceous carcinomas and 14 basal cell carcinomas (7 being of the morpheaform type and 7 nodular basal cell carcinomas) were tested with a monoclonal mouse antibody to human CK 19.
Results:  CK 19 was focally positive in 1/5 (20%) sebaceous adenomas, 8/16 (50%) of sebaceous epitheliomas and 1/6 (17%) of sebaceous carcinomas. Strongly positive expression of CK 19 was not seen in any of the sebaceous adenoma, sebaceous epithelioma or sebaceous carcinoma specimens. CK 19 was found to be strongly positive in 9/14 (64%) and focally positive in 2/14 (14%) of basal cell carcinomas.
Conclusion:  CK 19 expression can be helpful in differentiating sebaceous tumors (including sebaceous adenomas, sebaceous epitheliomas and sebaceous carcinomas) from basal cell carcinomas and may be a useful adjunct when these entities are included in the differential diagnosis.     

The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Paget's disease

Despite the similarity in clinical appearance, there is a significant difference in the prognosis between primary extramammary Paget's disease (EPD) and the pagetoid spread of underlying regional internal malignancy (secondary EPD, pagetoid phenomenon). Fifteen cases of primary EPD (11 carcinoma in situ and four invasive carcinoma), seven cases of secondary EPD (five colorectal adenocarcinoma and two urothelial carcinoma), and six cases of anal canal carcinoma were retrieved and analysed immunohistochemically using six kinds of monoclonal anticytokeratin antibodies. No expression of cytokeratins 1, 5, 10, 13 and 14 was observed in any cases examined in this study. All 15 cases of primary EPD had the immunophenotype cytokeratin (CK)7+/CK20-. CK20 expression was diffusely positive in six cases of secondary pagetoid spread (two urothelial carcinoma and four colorectal adenocarcinoma), and focally in one case (a colorectal adenocarcinoma). In anal canal carcinoma, three of six cases showed CK20 diffuse expression and the remaining three cases expressed CK20 focally. CK7 expression was observed in three of six cases of anal canal carcinoma and in two of five cases of secondary EPD associated with colorectal adenocarcinoma. The combination of CK7 and CK20 demonstrates these to be useful markers in distinguishing 'primary' EPD from a pagetoid spread of extracutaneous malignancies. Namely, immunophenotypes other than CK7+/CK20- in Paget cells suggest underlying regional internal malignancy.     

Immunohistochemical demonstration of D2-40 in basal cell carcinomas of the skin

Background: Recently, immunoreactivity to D2‐40, a monoclonal antibody to lymphatic endothelium, was shown in a subgroup of epidermal basal cells and the majority of squamous cell carcinomas, but the immunoreactivity to this antibody has not been examined in basal cell carcinomas (BCCs) of the skin. Methods: Expression of D2‐40 was analyzed together with that of cytokeratin (CK) 17, CK 19, CD34 and Ber‐EP4 by immunohistochemical methods in 10 non‐neoplastic skin tissue samples and 20 BCCs. Results: Immunoreactivity to D2‐40 was shown in the basal cells at the outer root sheath (ORS) of hair follicles, similar to the CK 19 expression pattern. CK 17 was strongly expressed in the suprabasal cells at the ORS. D2‐40 and CK 19 were focally expressed in 13/20 (65%) and 14/20 (70%) cases of BCCs, respectively, although the distributions of D2‐40 and CK 19 immunoreactivity were not always identical. However, BCC cells were constantly positive for CK 17 even tumor cells that were positive for D2‐40 and/or CK 19. Ber‐EP4 was diffusely expressed in all BCCs, and CD34 was focally expressed in 2/20 cases. Conclusion: Our results suggested that D2‐40 immunoreactivity in BCCs showed differentiation toward the ORS of hair follicles.     

Dilated pore: a case report and an immunohistochemical study of cytokeratin expression

We report a 71-year-old Japanese female with a dilated pore in the form of a nodule above her right eyebrow. Histologic examination revealed a flask-shaped, keratinous cystic structure that was continuous with the surface epidermis and had numerous elongated rete ridges in the lower portion. An immunohistochemical study using a panel of monoclonal antibodies against cytokeratins (CKs) and involucrin detected CK1 and CK10 in the suprabasal cells of the cystic structure. CK8 and CK19 expression was observed in the outermost layer of some elongated rete ridges; it was composed of pallisading columnar cells. Most parts of the outermost layer of the cystic structure stained positively with AE1 antibody. From these immunohistochemical findings, we speculated that the dilated pore in our case was an isolated clinical entity is a follicular tumor differentiating mainly toward the infundibulum and partly toward the isthmus.     

CD56: a useful marker for diagnosing Merkel cell carcinoma

BACKGROUND: Merkel cell carcinoma (MCC) of the skin is an aggressive but rare malignant neuroendocrine tumor. For its pathological diagnosis, we use a panel of immunohistochemical markers, such as cytokeratin 20 (CK 20), epithelial membrane antigen (EMA), chromogranin A, neuron specific enolase (NSE), synaptophysin, and Leu7 (CD57) to demonstrate its epithelial and neuroendocrine features. CD56, or neural cell adhesion molecule (NCAM), has been demonstrated recently as the tumor marker of the pulmonary neuroendocrine cell system. Its expression in MCC, however, has still rarely been investigated. Furthermore, in such very few previous studies on NCAM expression in MCC, all the tumor cells were not necessarily demonstrated to express NCAM. OBJECTIVES: To study the immunoreactivity of CD56 in MCC, especially using a monoclonal antibody of a clone 1B6, different from those adopted in the previous reports. METHODS: We reexamined CD56 expression immunohistochemically in five MCC cases, along with the conventional panel of markers described above, using paraffin-embedded tissue sections. RESULTS: CD56 revealed the most diffuse and intense positive staining, which was noted along the cell borders, in all specimens compared with other neuroendocrine tumor markers. CONCLUSIONS: The results of our study indicate that CD56, especially a new monoclonal antibody (clone 1B6), is a useful immunohistochemical marker for MCC.     

Immunohistochemical analysis of keratin expression in clear cell syringoma

Immunophenotypes, especially expression of cytokeratins, in 9 cases of clear cell syringoma were examined using antibodies against epithelial membrane antigen (EMA), and 17 kinds of monoclonal anti-keratin antibodies to investigate its histogenesis. In addition, 7 cases of conventional syringoma were selected for parallel assessment. Conventional syringoma expressed CK1 and CK10, which exists in the acrosyringium and the transitional portion between the acrosyringium and the dermal duct. Based on immunostaining with RCK102 and 35βH11, syringoma was thought to express CK5. Because expression of CK5 was observed in the basal cells of sweat duct ridge (lower acrosyringium) and the outer cells of the dermal duct, but not in the acrosyringium located at upper epidermis, we speculated that syringoma differentiated toward the transitional portion between the acrosyringium and the dermal duct. A comparative study of keratin expression between conventional and clear cell syringoma showed that there was no difference in the immunoreactivities. Based on the above observations, we confirmed that clear cell syringoma is a metabolic variant of conventional syringoma, and differentiates into the transitional portion between the acrosyringium and the dermal duct.     

Cytokeratin 15 expression in trichoepitheliomas and a subset of basal cell carcinomas suggests they originate from hair follicle stem cells

Trichoepitheliomas and many basal cell carcinomas appear to arise from the hair follicle, and in particular from the hair follicle bulge. This histogenesis is suggested from both morphological and immunohistochemical studies on tumor cells and stroma. Epithelial stem cells are thought to be important in tumorigenesis, and we previously localized a population of stem cells to the bulge area of the outer root sheath. We recently identified an anti-CD8 monoclonal antibody (DAKO clone C8/144B) that cross-reacts with cytokeratin 15 (K15), and serves as a specific marker for the bulge. In this study, we screened a series of trichoepitheliomas (n=13), basal cell carcinomas (n=37) and a variety of other skin tumors with this antibody. All trichoepitheliomas (100%) showed keratin 15 expression, while only a subset of basal cell carcinomas (27%) was K15-positive. Epidermal tumors, including squamous cell carcinomas, were K15-negative. Tumors of follicular derivation such as proliferating trichilemmal cysts were also K15-positive, while others such as pilomatricoma were K15-negative. Expression of K15 in trichoepitheliomas, some basal cell carcinomas and other follicular tumors suggests that these tumors are related to hair follicle stem cells in the bulge.