Expression of beta-catenin in basal cell carcinoma

Background beta-Catenin is a crucial member of the E-cadherin/catenin complex, which plays a major role in cell-cell adhesion. beta-Catenin is also known to be involved in signal transduction pathways. Many studies have demonstrated changes in the expression of beta-catenin in colorectal carcinomas, suggesting a role for beta-catenin in neoplastic development. Objectives Basal cell carcinoma (BCC) is a locally invasive tumour. The various subtypes show differences in biological behaviour. This study aimed to investigate the presence of differences in the immunoprofile of beta-catenin among histological variants of BCC. Methods Eighty BCCs were studied (32 nodular, 7 micronodular, 24 superficial and 17 infiltrative and morphoeic). Formalin-fixed, paraffin-embedded tissue sections were stained for beta-catenin using the avidin/biotin immunodetection technique. Results All the nodular BCCs showed membranous and weak cytoplasmic staining. Nuclear staining was seen in 15 of 32 (47%) cases, being stronger at the periphery of the nodules in 11 of 15 (73%) of these cases. In superficial BCCs the membranous staining was variable and cytoplasmic staining was increased. Nuclear staining was seen in 16 of 24 (67%) cases, being more notable at the periphery in 8 of 16 (50%) of these cases. All micronodular BCCs showed strong membranous staining, weak cytoplasmic and no nuclear staining. In the infiltrative and morphoeic BCCs membranous staining was completely lost at the advancing margins of the invading cell strands, with a marked increase in cytoplasmic staining; nuclear staining was observed in all these tumours. Conclusions The expression of beta-catenin varied between different types of BCC. Nuclear localization was most notable in the infiltrative and morphoeic variants, followed by the superficial variant, and seen least in nodular BCC. Its prominence at tumour margins suggests that this may be associated with more aggressive types of invasion.     

Expression of CD10 in basal cell carcinoma

We investigated the expression of CD10 by an immunohistochemical method in 51 basal cell carcinomas (BCCs), eight pilomatricomas, five trichoblastomas, two trichofolliculomas, three sebaceomas, five sebaceous carcinomas, ten syringomas, two spiradenomas, ten poromas, four porocarcinomas, one eccrine duct carcinoma (not otherwise specified, NOS), six mixed tumors of apocrine origin, and nine squamous cell carcinomas (SCCs). We detected strong expression of CD10 in tumor cells of BCC (86%), and found that the smaller the number of positive tumor cells, the larger the number of positive stromal cells, in particular in sclerosing BCCs. Spearman's rank correlation test revealed a significant negative correlation in BCCs between the expression of CD10 in tumor cells and that in stromal cells (P = 0.001). In all pilomatricomas (100%) and in four trichoblastomas (80%), strong expression was also detected in tumor cells. There was no detectable expression in trichofolliculomas. One sebaceoma (33%) and two sebaceous carcinomas (40%) expressed CD10 in a similar fashion to BCCs. All tumors of eccrine gland origin, including syringoma, spiradenoma, poroma, porocarcinoma, and eccrine duct carcinoma (NOS), did not express CD10. Five mixed tumors (83%) were immunopositive. In SCC, CD10 was overexpressed only in the stromal cells. These findings support the hypothesis that BCC is derived from the folliculo-sebaceous apocrine unit, especially having the same origin as trichoblastoma and pilomatricoma. CD10 might be an indicator of tumor invasiveness if it is expressed in stromal cells, while it might be a marker of follicular differentiation if it is expressed in the actual tumor cells of cutaneous epithelial neoplasms.     

Expression of ZNF396 in basal cell carcinoma

Zfp191 represses differentiation and keeps various cells in the stem/progenitor stage. Here, we report that a Zfp191 homolog protein, ZNF396, is expressed in basal cell carcinoma (BCC) and possibly represses the expression of a Notch system effector molecule, Hes1 (hairy and enhancer of split-1), and prevents BCC cells from undergoing Notch-mediated squamous cell differentiation. ZNF396 immunoreactivity was found in the nucleus of 35 of 38 cutaneous BCC and 4 of 74 squamous cell carcinoma tissue specimens. In non-tumorous epidermal tissues, ZNF396 immunoreactivity was restricted in basal cells. siRNA-mediated silencing of ZNF396 induced the expression of Notch2, Hes1, and involucrin in cultured BCC cells. Finally, we found that siRNA-mediated silencing of ZNF396 gene inhibited the proliferation of TE354.T basal cell carcinoma cells. ZNF396 might repress Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous differentiation in BCC.     

皮肤基底细胞癌组织中血管内皮细胞生长因子受体-2的表达

目的 研究血管内皮生长因子受体-2(VEGFR-2)在皮肤基底细胞癌(BCC)组织中的表达情况.方法 提取BCC组织的mRNA,以RT-PCR法检测标本中VEGFR-2mRNA的表达.同时应用蛋白质印迹法检测VEGFR-2蛋白的表达,免疫荧光法检测VEGFR-2在BCC组织中的定位.结果 BCC组织标本mRNA和蛋白水平中均可以检测到VEGFR-2的表达,并较正常人对照有显著增加.VEGFR-2在BCC细胞主要表现为膜性分布.结论 皮肤BCC组织细胞能够高异常表达VEGFR-2,可能是导致BCC细胞肿瘤性增殖的原因之一.     

Expression of vascular endothelial growth factor in basal cell carcinoma and cutaneous squamous cell carcinoma of the head and neck

BACKGROUND: Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) can both arise from any cutaneous epithelial surface. BCC are slow growing and rarely metastasise, whereas SCC are usually more aggressive. It is likely that the angiogenic process plays a key role in determining rate of growth and propensity for dissemination. Angiogenesis is a complex process requiring many factors and a pivotal group of proteins involved in this process is vascular endothelial growth factor (VEGF). METHODS: Immunohistochemical expression of VEGF was assessed in 44 cases of BCC and 41 cases of cutaneous SCC from the head and neck region. RESULTS: VEGF was expressed by blood vessel endothelial cells in both adjacent skin and tumour, and in the basal keratinocyte layer of epidermis. In BCC, VEGF was expressed by tumour epithelial cells, predominantly at the invasive tumour front, in 24/44 cases and its expression was significantly greater than in adjacent skin (p = 0.038). More widespread VEGF expression was found in 32/41 cases of SCC, and it was significantly associated with the degree of tumour differentiation (p < 0.001). CONCLUSIONS: The patterns of VEGF expression in BCC and SCC may help to explain the different behaviour that is usually seen with these tumours.     

Fascin-1蛋白在基底细胞癌及鳞状细胞癌中的表达

目的 探讨fascin-1蛋白与基底细胞癌及鳞状细胞癌局部侵袭的相关性。方法 免疫组化方法对10例正常皮肤组织、13例皮肤基底细胞癌（8例结节型、5例浅表型）、24例皮肤鳞状细胞癌（11例原位鳞状细胞癌,13例侵袭性鳞状细胞癌均无转移）进行fascin-1染色,计算机图像分析系统进行观察及定量分析。结果 Fascin-1蛋白在原位鳞状细胞癌（平均光密度0.1152 ± 0.04574）、侵袭性鳞状细胞癌（平均光密度0.1257 ± 0.03096）中的表达明显高于正常上皮组织（平均光密度0.0293 ± 0.00981,P ＜ 0.05）。在结节型基底细胞癌（平均光密度0.0808 ± 0.05642）、浅表型基底细胞癌（平均光密度0.0806 ± 0.04346）中表达差异无统计学意义,但明显高于正常上皮组织（平均光密度0.0293 ± 0.00981,P ＜ 0.05）。结论 在基底细胞癌及鳞状细胞癌中,fascin-1蛋白表达上调可能与肿瘤的局部侵袭相关。     

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.     

PTEN和Survivin在基底细胞癌中的表达

目的:探讨抑癌蛋白PTEN和凋亡抑制因子Survivin在基底细胞癌(BCC)中的表达及其意义。方法:采用免疫组化SP法检测20例BCC和30例正常人皮肤中PTEN、Survivin的表达和分布。结果:20例BCC标本中,PTEN表达下调(P<0.05),Survivin表达增高(P<0.001)。PTEN和Survivin的表达无相关性。结论:PTEN异常低表达和Survivin异常高表达可能与BCC的发生、发展有关。     

bFGF、NGF在基底细胞癌表达的研究

目的：探讨基底细胞碱性成纤维细胞生长因子（bFGF）和神经生长因子（NGF）在基底细胞癌发病中的可能作用。方法：用免疫组化的方法对10例基底细胞癌进行了检测。结果：10例基底细胞癌均表达bFGF及NGF。结论：bFGF及NGF可能在基底细胞癌的发生中起一定作用。     

真核细胞翻译起始因子4E在皮肤基底细胞癌中的表达

目的：检测皮肤基底细胞癌中真核细胞翻译起始因子4E(eIF4E)的表达。方法：采用免疫组化PV-9000法和Real-time PCR法分别检测20例皮肤基底细胞癌及20名健康皮肤组织中eIF4E蛋白及mRNA的表达。结果：基底细胞癌和健康皮肤组织中eIF4E蛋白MOD值分别为(0.198±0.031)和(0.096±0.015),mRNA相对表达量分别为(2.32±1.00)和(1.24±0.17),差异具有统计学意义(P<0.05)。结论：eIF4E可能参与皮肤肿瘤的发病过程。     

Expression of stem cell factor in cutaneous mastocytosis

Stem cell factor has recently been identified as a potent growth factor for bone marrow stem cells, melanocytes and mast cells. In order to evaluate its possible role in human mastocytosis, skin lesions from 13 patients with urticaria pigmentosa and five patients with mastocytomas, and normal skin specimens from five healthy donors were studied by immunohistochemistry, using polyclonal and monoclonal (hkl-12) antibodies against stem cell factor, and a monoclonal antibody (YB5.B8) against its receptor, the c-kit proto-oncogene product. Stem cell factor expression was noted in all sections studied, with an equal distribution pattern for both antibodies, but a weaker intensity with the hkl-12 reagent. Cytoplasmic staining was noted in keratinocytes, Langerhans cells, sweat gland ductal lining cells, mast cells, endothelial cells and spindle-shaped dermal stromal cells. An intense, diffusely granular reaction pattern was noted in all cells, except for a sparse, coarsely granular pattern in mast cells and stromal cells. In urticaria pigmentosa, staining was weaker in keratinocytes, but more prominent in Langerhans cells. In all sections, toluidine blue-positive mast cells and TA 99-positive basal epidermal melanocytes were the only cells to react with the c-kit antibody. Mastocytomas and urticaria pigmentosa lesions thus exhibit different patterns of stem cell factor expression. However, a possible pathogenetic role of this factor in mastocytosis remains to be determined.     

SGK1在日光性角化病、基底细胞癌及鳞状细胞癌中的表达

目的：检测SGK1在日光性角化病（AK）、基底细胞癌（BCC）及鳞状细胞癌（SCC）中的表达。方法：采用免疫组化SABC法检测SGK1在25例正常皮肤(NS)、25例AK、28例BCC、28例皮肤鳞状细胞癌标本中的表达。结果：NS、AK、BCC和SCC标本中,SGK1阳性细胞率分别为（40.03±14.42）%,（36.63±14.28）%,（52.82±18.73）%和（52.58±20.13）%。BCC组和SCC组分别与NS组比较,差异均有统计学意义（Ps<0.05）。各组SGK1染色阳性细胞率>50%的标本分别为6例（24%）,3例（12%）,16例（57.14%）和14例（50%）,BCC组和SCC组分别与NS组比较,差异均有统计学意义（Ps<0.05）。结论：SGK1的高表达可能与基底细胞癌及鳞状细胞癌的发病有关。     

皮肤鳞状细胞癌和基底细胞上皮瘤中c—myc蛋白的表达

利用鼠抗单克隆抗体ｃ－ｍｙｃ９Ｅ１０．３,过氧化物酶的方法,研究用福尔马林固定,石蜡包埋的鳞状细胞瘤（ＳＣＣ）３０例和基底细胞上皮瘤（ＢＣＥ）３１例皮损标本中ｃ－ｍｙｃ蛋白的表达情况,其中ＳＣＣ中ｃ－ｍｙｃ蛋白阳性８例,染色是核内着色,强阳性,而ＢＣＥ中仅１例阳性,因此,推测ｃ－ｍｙｃ中仅１例阳性。因此,推测ｃ－ｍｙｃ蛋白过表达可能是恶性肿瘤的一种恶性程度标志。     

Foxp1及Ki-67在皮肤基底细胞癌的表达

目的:检测皮肤基底细胞癌(BCC)组织中Foxp1和Ki-67蛋白的表达.方法:采用免疫组化方法检测BCC组织石蜡切片中Foxp1和Ki-67蛋白的表达.结果:40例BCC标本中Foxp1蛋白的表达率为82.5%,Ki-67蛋白的表达率为75%,均显著高于对照组(均P＜0.01).结论:Foxp1和Ki-67可能参与BCC的发生和发展.     

Expression of p53 in arsenic-related and sporadic basal cell carcinoma

BACKGROUND: The TP53 gene has been shown to have an important role in the genesis of sporadic, presumably mainly sunlight-related, basal cell carcinoma (BCC). However, its role in arsenic-related BCCs is not clear, although the trivalent form of arsenic has been long recognized as a cause of BCC. Arsenic treatment has been shown to cause hypermethylation of the TP53 gene in lung carcinoma cell lines, but it is not known if this occurs in vivo in arsenic-related BCCs. OBJECTIVE: To compare the immunohistochemical expression of the p53 protein in arsenic-related and sporadic BCCs to determine if the expression pattern is consistent with gene silencing. SETTING: A research institute and hospital in Australia. CASES: One hundred seventeen white patients with 121 sporadic BCCs and 21 white patients with 92 arsenic-related BCCs. MAIN OUTCOME MEASURES: The expression and the intensity of p53 were scored semiquantitatively. Statistical analysis was performed using the chi2 test. RESULTS: Arsenic-related BCCs express p53 less often and at a lower intensity than sporadic BCCs (P = .001; 2-tailed test). The BCCs from sun-exposed sites, whether arsenic related or sporadic, more frequently showed overexpression of p53 than those from less-exposed areas (P = .004; 2-tailed test). The more aggressive subtypes of BCC show a higher level of expression of p53 than the less aggressive forms (P = .04; 2-tailed chi2 test). CONCLUSIONS: These results are consistent with the hypothesis that the TP53 gene is down-regulated by methylation in arsenic-related BCC, particularly those from less-exposed sites. However, an alternative possibility is that mutations in TP53 that stabilize the protein are less common in arsenic-related BCCs. Further analysis will be necessary to distinguish between these hypotheses.     

Infiltrative basal cell carcinoma occurring in sites of biopsy-proven nodular basal cell carcinoma

Over 200 basal cell carcinomas (BCCs) are biopsied and subsequently excised each year at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). A focal infiltrative pattern developed in the region of the biopsy scar in the re-excision specimens of 20 cases out of approximately 400 BCCs (< 5%) examined histopathologically over a 2-year period. The patient population included predominantly male, elderly Caucasians (mean age 71), and all tumors fulfilled clinical and histologic criteria for nodular BCC at the time of initial punch or shave biopsy. No patient showed recurrence of tumor following simple re-excision with 2–3 mm surgical margins, with a mean follow up of 25.4 months after excisional surgery. These neoplasms had a more benign clinical course, possibly related to scar formation in healing sites of previously biopsied nodular BCC, rather than true aggressive-growth BCC. The authors conclude that a focal infiltrative pattern in a re-excision specimen may occur histologically as a scar-induced pattern which mimics an aggressive-growth BCC, but does not appear to have the same prognosis. We believe this is an important histologic observation, as recognition of biopsy scar changes in an excisional specimen of BCC may help to distinguish it from true aggressive-growth BCC.     

Akt和mTOR在皮肤基底细胞癌中的表达

目的 检测Akt和雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）在皮肤基底细胞癌( basal cell carcinoma, BCC)中的表达情况,探讨Akt/mTOR信号通路在BCC发病机制中的作用及其临床意义。方法 免疫组织化学方法检测37例BCC以及16例正常皮肤标本中的Akt和mTOR蛋白的表达情况。结果 BCC中Akt蛋白的阳性表达率为62.2%,mTOR蛋白的阳性表达率为83.8%,与正常皮肤组织中Akt蛋白的阳性表达率12.5%和mTOR蛋白的阳性表达率37.5%相比,显著增高(均为P<0.05)。Akt和mTOR的表达水平在BCC中存在正相关,有统计学意义(均为P<0.05)。结论 Akt和mTOR在BCC中的过度表达,提示Akt/mTOR通路可能是BCC发生发展的机制之一。