A trip through the signaling pathways of melanoma

Many cellular signaling pathways are involved in the development of cancer. Depending on the tumor entity, the nature as well as the mode of activation can differ. Some signaling pathways frequently show changes as all tumor cells have to fulfill some basic requirements such as independence from growth factors or insensitivity against apoptosis. In this review, the possibilities of a tumor to manipulate signaling pathways to reach these goals are exemplified based on an archetypical melanoma cell. In addition, new therapeutic options based on the knowledge of signaling pathways will be discussed.     

Immunoreactive p53 and metallothionein expression in duct carcinoma in situ of the breast

 Immunocytochemically detectable MT and p53 have been found more commonly in comedo DCIS of the breast with high-grade cytology. The aim of this study is to confirm these findings and to investigate the relationship between MT and p53 in a single large series of cases of DCIS of the breast. To this end, 127 cases of DCIS were classified histologically according to architecture, cytonuclear differentiation (grade), presence and extent of intraduct necrosis, and using the Van Nuys system. Sections were immunostained for p53 and MT (E9) using established techniques, and the extent and intensity of staining were assessed semi-quantitively. The results confirmed that there was generally more MT and p53 positivity in poorly differentiated (grade 3) DCIS with extensive necrosis and that MT expression was greater in grade 2 lesions than p53 expression. However, overall there was no statistically significant correlation between p53 and MT staining. The results indicate that MT and p53 overexpression may arise from independent mechanisms in early breast neoplasia. Received: 3 July 1996 / Accepted: 5 November 1996     

Immunohistochemical Study of Colorectal Polyps with Antibodies against CEA,CA19-9, CA125, CA15-3 (DF3), PCNA and p53

Abstract: We analyzed the expression of CEA, CA19-9, CA125, CA15-3 (DF3), PCNA and p53 immunohistochemically in 14 tissue specimens of mucosal cancers in adenoma, seven tubulovillous adenoma specimens, and 16 tubular adenoma specimens. The rates of positive staining for mucosal cancer in adenoma, tubulovillous adenoma and tubular adenoma specimens, respectively, were: for CEA: 100%, 85.7% and 75%; for CA19-9: 71.4%, 71.4% and 56.2%; for CA125:0%, 0% and 0%;for CA15-3 (DF3): 64.3 %, 0% and 0 %; for PCNA: 100%, 88.9% and 56.2%; and for p53: 35.7%, 0% and 0% . The results suggest that the expressions of CEA, CA19-9, CA15-3 (DF3), PCNA and p53 are related to colorectal tumorigenesis. None of the specimens studied showed staining for CA125, suggesting that CA125 is not involved in the early stages of colorectal carcinogenesis. There was no significant difference in the rates of positive staining for CEA and CA19-9 among mucosal cancer in adenoma, tubular adenoma and tubulovillous adenoma specimens. However, the rates of positive staining for PCNA and p53 were significantly higher in mucosal cancer in adenoma specimens than for tubular adenoma specimens (p<0.05), and the rate of CA15-3 (DF3) positive staining was significantly higher for mucosal cancer in adenoma than for tubulovillous adenoma (p<0.01) and tubular adenoma (p< 0.001) specimens. Therefore, the CA15-3 (DF3) antigen is an immunohistochemical marker for colorectal carcinomas. The present results suggest that CA15-3 (DF3), PCNA and p53 play important roles in the genesis of colorectal adenomas.     

毛喉萜对人肝癌细胞增殖影响的实验研究

目的　探讨毛喉萜 (Forskolin)的抗肝癌作用。方法　采用克隆形成、MTT比色法观察毛喉萜对SMMC 772 1细胞的作用 ,并利用免疫细胞化学方法检测其对rasp2 1、p5 3蛋白表达的影响。结果　毛喉萜可明显抑制SMMC 772 1细胞的增殖 ,其抑制率与剂量呈正相关 (P <0 .0 1 ) ,经毛喉萜处理后 ,rasp2 1、p5 3蛋白表达均有明显下降。结论　毛喉萜能明显抑制肝癌SMMC 772 1细胞增殖 ,其作用可能与降低rasp2 1、p5 3蛋白表达有关。     

Expression of p27 and p53: comparative analysis of uterine carcinosarcoma and endometrial carcinoma

The aim of the study was to assess both p27 and p53 expression in the stromal and epithelial component of carcinosarcoma and to assess if their expression in the latter is different than in endometrial carcinoma. Immunohistochemical staining for p27 and p53 was performed on paraffin-embedded tissue blocks of 18 uterine specimens with carcinosarcoma and their expression assessed. Their expression in the epithelial element was also compared to that in 35 paraffin-embedded tissue blocks of endometrial endometrioid carcinoma. Reduced p27 expression was observed in a similarly high proportion of the stromal (77.8%) as well as of the epithelial component (66.7%) of carcinosarcoma. Although statistically not significant, the proportion of reduced p27 expression in endometrial carcinoma (85.7%) was higher than in the epithelial element of carcinosarcoma. The percentage of p53 overexpression in both elements of carcinosarcomas and in endometrial carcinomas was low and also similar (27.8 and 20.0%, respectively). Our results indicate that reduced p27 expression is common and p53 overexpression is infrequent in carcinosarcoma. Their similar rates of expression in the stromal and epithelial elements of the tumor support the contention of a monoclonal origin of carcinosarcoma. Unexpectedly, reduced p27 expression is more common in endometrial carcinoma than in the epithelial element of carcinosarcoma, in spite of the less favorable prognosticators and outcome in the latter. Further studies of p27 expression in carcinosarcoma are indicated to establish its clinical value in this aggressive malignancy.     

p53、nm23蛋白在宫颈鳞癌中的表达及其临床意义

目的研究p53、nm23基因在宫颈鳞癌中的表达及其临床意义.方法采用免疫组织化学S-P法检测45例宫颈鳞癌组织、10例宫颈上皮内瘤变和10例正常宫颈鳞状上皮中p53、nm23蛋白的表达.结果p53、nm23蛋白在宫颈鳞癌中的阳性表达率分别为64.44%、46.67%;在CIN中阳性表达率分别为0、30.00%;在NE组均无表达.p53蛋白在宫颈鳞癌中阳性表达与在CIN、NE中的不表达差异均有显著性(P＜0.01).nm23蛋白在宫颈鳞癌组织中的阳性表达与在NE中的不表达差异有显著性(P＜0.05),但与在CIN中的表达差异无显著性(P＞0.05);与病理学分级、淋巴结转移均呈负相关(P＜0.05,P＜0.01).结论p53、nm23基因参与了宫颈鳞癌的发生发展过程.p53蛋白的过表达是宫颈癌组织恶性变的生物学标志;检测nm23蛋白对判断宫颈癌淋巴结转移和预后有重要意义.     

皮肤鳞状细胞癌中p53、bcl-2和c-myc的表达及意义

目的 研究p53、bcl—2和c—myc在皮肤鳞状细胞癌中的异常表达及其与癌分化程度的关系。方法 应用免疫组织化学S-P法检测58例皮肤鳞状细胞癌中p53、bcl—2和c—myc的表达水平。结果 58例皮肤鳞状细胞癌中p53、bcl-2和c—myc的阳性表达率分别为48．3％、67．2％和32．8％。结论 p53、bcl—2和c—myc异常表达在皮肤鳞状细胞癌的发生、发展中起重要作用，并与皮肤癌的恶性程度有关。