Immunohistochemical Expression of p16, p21, p27 and Cyclin D1 in Oral Nevi and Melanoma

The acquisition of abnormalities at G1/S is considered a crucial step in the genesis and progression of melanoma. The expression of cell cycle regulators has also been used in various neoplasms as an adjunct to diagnosis. The aim of this study was to compare the expression of p16, p21, p27 and cyclin D1 in oral nevi and melanomas. Expression of these cell cycle regulatory proteins was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas. p16 and p27 were highly expressed in intramucosal nevi, whereas p21 and cyclin D1 expression was higher in oral melanomas. The results indicate that p21 and cyclin D1 may be involved in the development of oral melanomas, and eventually they may be useful in the differential diagnoses of oral benign and malignant melanocytic lesions.     

Cyclin D3、Cyclin D1、p27KIP1在膀胱尿路上皮细胞癌中的表达及其关系

目的 探讨膀胱尿路上皮细胞癌(UCCB)组织中Cyclin D3、Cyelin D1和p27KIP1的表达及关系.方法 采用免疫组织化学方法测定50例UCCB组织、癌旁组织及15例正常膀胱黏膜组织的Cyelin D3、Cyelin DI和p27KIP1表达情况;逆转录-聚合酶链反应(RT-PCR)方法测定CyclinD3 mRNA的表达情况.结果 Cyclin D3蛋白在UCCB、癌旁黏膜及正常膀胱黏膜中的表达率分别为32.00%(16/50)、12.00%(6/50)和6.67%(1/15),在UCCB组织中的表达高于癌旁黏膜和正常膀胱黏膜中的表达,差异有统计学意义(P<0.05),和病理分级、肿瘤大小及1年内肿瘤复发明显相关(P<0.05);Cyelin D3 mRNA在膀胱癌组织与癌旁组织和正常组织间,差异均有统计学意义(P<0.01).CycLin D1阳性率为80.00%(40/50),和病理分级及1年内肿瘤复发明显相关(P<0.05);p27KIP1阳性率为46.00%(23/50),和病理分级及1年内肿瘤复发明显相关(P<0.05).p27KIP1蛋白与Cyclin D3蛋白、Cyefin D1蛋白在UCCB中的表达呈负相关(r=-0.5472,P<0.01:r=-0.5417,P<0.01).Cyelin D3和Cyclin D1蛋白表达呈正相关(r=0.3430,P(0.05).结论 UCCB组织中Cyclin D3、Cyclin D1和p27KIP1表达明显相关,三者联合检测对UCCB的诊断治疗和估计预后有一定意义.     

cyclin D1和p27在人皮肤血管瘤中的表达及意义

目的　探讨cyclinD1和p2 7蛋白在血管瘤发生、发展及退化过程中的表达状况及其意义。方法　采用免疫组织化学方法 (S-P法 )检测人皮肤血管瘤增生期、退化期及正常皮肤组织中cyclinD1和 p2 7的表达水平 ,并结合第Ⅷ因子相关抗原的免疫组织化学染色证实表达cyclinD1和 p2 7的细胞是血管内皮细胞。利用计算机图像分析技术测量不同时期血管瘤组织和正常皮肤组织cyclinD1和p2 7表达的平均光密度和平均阳性面积率。 结果　增生期血管瘤内皮细胞cyclinD1表达水平高于退化期 ,差异有显著意义 (P <0 .0 5 ) ,退化期血管瘤内皮细胞cyclinD1表达水平与正常皮肤组织相比 ,差异无显著意义 (P >0 .0 5 ) ;而增生期血管瘤内皮细胞p2 7表达水平低于退化期 ,差异有显著意义(P <0 .0 0 5 ) ,退化期血管瘤内皮细胞 p2 7表达水平与正常皮肤组织相比 ,差异有极显著意义 (P <0 .0 0 1)。 结论　cyclinD1和p2 7可能通过介导血管瘤内皮细胞增殖和血管生成而在血管瘤的发生、发展及退化过程中起重要作用。     

cyclin D1和p27在人皮肤血管瘤中的表达及意义

目的探讨cyclinD1和p27蛋白在血管瘤发生、发展及退化过程中的表达状况及其意义.方法采用免疫组织化学方法(S-P法)检测人皮肤血管瘤增生期、退化期及正常皮肤组织中cyclinD1和p27的表达水平,并结合第Ⅷ因子相关抗原的免疫组织化学染色证实表达cyclinD1和p27的细胞是血管内皮细胞.利用计算机图像分析技术测量不同时期血管瘤组织和正常皮肤组织cyclinD1和p27表达的平均光密度和平均阳性面积率.结果增生期血管瘤内皮细胞cyclinD1表达水平高于退化期,差异有显著意义(P＜0.05),退化期血管瘤内皮细胞cyclinD1表达水平与正常皮肤组织相比,差异无显著意义(P＞0.05);而增生期血管瘤内皮细胞p27表达水平低于退化期,差异有显著意义(P＜0.005),退化期血管瘤内皮细胞p27表达水平与正常皮肤组织相比,差异有极显著意义(P＜0.001).结论cyclinD1和p27可能通过介导血管瘤内皮细胞增殖和血管生成而在血管瘤的发生、发展及退化过程中起重要作用.     

Clinicopathologic study of thymic epithelial tumors

OBJECTIVE: We analyzed clinicopathologic characters and long-term results of 11 thymic epithelial tumors. METHODS: Five cases of thymic carcinoma and 6 cases of thymoma treated in our hospital from September 1991 to June 2002 were retrospectively analyzed. RESULTS: The histological subtypes of thymic carcinoma were basaloid carcinoma in 2 cases, epidermoid non-keratinizing carcinoma in 1 case, undifferentiated carcinoma in 1 case and sarcomatoid carcinoma in 1 case. Four cases underwent chemotherapy and radiotherapy. Three cases underwent midsternal thoracotomy, 1 had total resection and 2 had exploratory thoracotomy due to tumor invasion of the right upper lobe and cardiac sac. Two cases of basaloid carcinoma had been alive more than 10 years since the operation. The histological subtypes of thymoma were 1, 2, 1, 1 and 1 cases with type A, AB, B 1, B 2 and B 3. All cases underwent midsternal thoracotomy, 4 cases had thymothymectomy and 2 cases had extended thymothymectomy. Five cases have been alive since the operation. Strong immunoreactivity for bcl-2 and p 53 expression of epidermoid non-keratinizing carcinoma and undifferentiated carcinoma were seen. ki-67 labeling index of epidermoid non-keratinizing carcinoma and undifferentiated carcinoma and type B 3 thymoma were higher than those of the other carcinomas and thymomas.     

脑胶质瘤中p27和Cyclin D1的表达及意义

目的探讨人脑胶质瘤组织中Cyclin D1和p27蛋白的表达及其与细胞凋亡的关系。方法采用免疫荧光法检测脑胶质瘤和非肿瘤组织中p27和Cyclin D1蛋白的表达,并用图像分析系统作定量分析。原位末端标记（TUNEL）法检测细胞凋亡情况,计算其凋亡细胞密度。结果p27蛋白的表达强度随肿瘤恶性程度增高而下降;Cyclin D1蛋白的表达强度随肿瘤恶性程度增加而升高;并且p27基因表达强度与细胞凋亡密度呈显著正相关。结论p27表达下降或缺失和Cyclin D1的过表达与脑胶质瘤的发生、发展密切相关。p27蛋白表达的下降可能导致肿瘤细胞凋亡减少。p27kip1有望成为胶质瘤基因治疗的新策略。     

Lymphogenous and hematogenous metastasis of thymic epithelial tumors

BACKGROUND: A TNM classification has been established for various tumors. However, the TNM classification of thymic epithelial tumor has not been established yet. METHODS: We received replies to a questionnaire on thymic epithelial tumors from 115 institutes. We compiled a database of 1,320 patients with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41 thymic carcinoids) who were treated between 1990 and 1994. We used a tentative TNM classification of thymoma presented by Yamakawa and associates in 1991. The regional lymph nodes of the thymus were classified into three groups: anterior mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic lymph nodes (N3). RESULTS: The rate of lymphogenous metastasis in thymoma, thymic carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma, 69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2, and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis demonstrated that survival of patients with thymoma was dependent on the clinical stage of Masaoka and complete resection. In thymic carcinoma, survival was dependent on lymph node metastasis and complete resection. CONCLUSIONS: The N factor was one of the predictors of survival in thymoma and thymic carcinoma. However, M factor showed less influence on survival than T or N factors.     

Clinical and pathological aspects of thymic epithelial tumors

A histological classification of thymic epithelial tumors was presented by the World Health Organization (WHO) in 1999 and again in 2004 following slight modifications, in which thymic epithelial tumors were categorized as thymomas and thymic carcinomas. Whereas thymoma is defined as an organotypic (thymuslike) tumor, thymic carcinoma is a malignant epithelial neoplasm with a morphology similar to that of malignant neoplasms arising from other organs. Herein, the recent progress in research of thymic epithelial tumors is reviewed with reference to the WHO histological classification system, with the focus on thymomas. Thymomas are classified into five types—A, AB, B1, B2, B3—according to the shape and atypia of their epithelial cells as well as the abundance of lymphocytes. The invasiveness, prognosis, and genetic imbalance of thymomas have been shown to be related to this classification system. Myasthenia gravis is frequently associated with types B1 and B2. The WHO histological classification of thymomas is not only useful for treatment but reflects their biological characteristics, including genetic alterations. Advances are expected in future studies of thymomas from the standpoint of their clinical, pathological, and biological aspects. This review was submitted at the invitation of the editorial committee.     

STAT3、p27在皮肤恶性黑色素瘤中的表达

目的：了解STAT3、p27在皮肤恶性黑色素瘤（cutaneous malignant melanoma,CMM）发病机制中的作用。方法：采用免疫组化SP法检测了54例皮肤恶性黑色素瘤、22例交界痣、20例正常皮肤组织中STAT3、p27的表达,并分析STAT3、p27两者的相关性。所有数据采用SPSS17．0统计软件包行卡方检验及相关性分析,检验水准仅=O．05,χ^2分割检验标准α=0．0167。结果：①STAT3蛋白在CMM中阳性表达率为77．8％,在皮肤交界痣和正常皮肤中阳性表达率分别为45．0％、35．O％。CMM与皮肤交界痣、正常皮肤相比差异有统计学意义（P〈0．0167）,皮肤交界痣与正常皮肤相比差异无统计学意义（P〉0．0167）;②p27蛋白在CMM中阳性表达率为16．7％,在皮肤交界痣和正常皮肤中阳性表达率分别为86．4％、95．O％。CMM与皮肤交界痣、正常皮肤相比差异有统计学意义（P〈0．0167）。皮肤交界痣与正常皮肤相比差异无统计学意义（P〉O．0167）：③STAT3表达与p27表达呈负相关（P=-0．000,r= 0．478）。结论：STAT3蛋白可能在CMM的发生、发展中发挥促进作用;p27蛋白在CMM发生中可能起抑癌作用。     

Prognosis of surgically treated thymic epithelial tumors

This study was performed to clarify the prognosis of patients with surgically treated thymic epithelial tumors. The records of 131 patients who underwent surgical treatment during 1985-2005 were retrospectively reviewed. Pathologic review was done according to the WHO classification of tumors of the thymus. Patients characteristics were: 76 male and 55 fimale; average age 53 (range 20-80) years; tumor stage was stage I in 42, stage II in 43, stage III in 23, stage IVa in 15, stage IVb in 1, and thymic carcinoma (squamous cell carcinoma) in 7 based on Masaoka's staging. There were 7 cases of type A, 23 of type AB, 30 of type B1, 27 of type B2, 29 of type B3, and 15 of type C. Surgical procedures performed were 5 partial resections, 5 tumoretomies, 5 thymectomies, 65 extended thymectomies, 4 tumorectomies plus adjunctive resections of surrounding tissue, and 51 extended thymectomies plus tumorectomies plus adjunctive resections of surrounding tissue including the pleura, pericardium, lung, and great vessels. Five-, 10-, and 15-year survival rates by Masaoka stage were 100%, 100%, and 100% in stage I; 100%, 100%, and 87.5% in stage II; 100%, 87.5%, and 87.5% in stage III; 71.1%, 53.3%, and 53.3% in stage IVa; and 42.9%, 42.9%, and 0% in thymic carcinoma. The prognosis of patients with stage IVa and thymic carcinoma was thus significantly poorer compared with that in the other groups. According to the WHO classification, the 5-year survival rate of type A was 100%, and the 5-, 10-, and 15-year survival rates were 100%, 100%, and 100% in type AB; 100%, 100%, and 75.0% in type B1; 92.6%, 86.4%, and 86.4% in type B2; 95.5%, 95.5%, and 81.8% in type B3; and 57.1%, 42.9%, and 0% in type C. The survival rate of patients with type C was the poorest and there was a significant difference between type C and all other groups. The prognosis of patients with thymic epithelial tumors after resection is thought to be determined by histologic classification and clinical invasiveness. In particular, patients with type B3 and type C thymomas should be considered for multidisciplinary treatment.     

p27kipl和cyclin D1在肾细胞癌中的表达及生物学意义

目的 探讨细胞周期蛋白依赖性激酶抑制蛋白p27kipl(p27)和细胞周期蛋白D1（Cyclin D1)与肾癌生物学行为的关系。方法 采用免疫组化SP法测定41例肾透明细胞癌及21例正常肾组织石蜡切片中p27蛋白和Cyclin D1蛋白的表达。结果 p27在正常肾组织的阳性率分别为82．4％、57．1％、20．0％,p27表达与肾癌的分级呈负相关（P＜0．01）。Cyclin D1在正常肾组织中的阳性率为33．3％。在肾癌组织中的阳性率为68．3％（P＜0．01）。Cyclin D1在G1、G2、G3肾癌组织的阳性率分别为88．2％、71．4％、30．0％,Cyclin D1蛋白的表达与肾癌的分级亦呈负相关（P＜0．05）。p27和Cyclin D1间在肾癌中的表达呈正相关（P＜0．001）,r=0.6。结论 p27和Cyclin D1与肾癌的组织学分级呈负相关,提示p27和Cyclin D1有可能作为判别肾癌分化 程度的标志物,并可能成为判断预后的有用指标。     

Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27(Kip1) in urothelial carcinoma: correlation with other cell-cycle-related proteins (Rb, p53, Ki-67 and PCNA) and clinicopathological features

INTRODUCTION: The expression pattern of cyclins D1 and E, as well as cyclin-dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their relationship to tumour behaviour and patients' prognosis was examined in 142 urothelial cell carcinomas. The expression of these proteins was also analyzed along with other cell-cycle-related proteins such as: p53, pRb and the proliferation-associated indices Ki-67 and proliferating cell nuclear antigen (PCNA). PATIENTS AND METHODS: These molecule markers were localized immunochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10), and anti-p27 (1B4) in 142 patients with urothelial cell carcinoma. RESULTS: Focal positivity (<10% of tumour cells) or the absence of cyclin D1 immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin D1 expression was correlated with tumour grade and stage as well as with the existence of in situ component. In addition, cyclin D1 expression was positively correlated with p21(Waf1/Cip1) and p27(Kip1) and inversely with the Ki-67 score. Focal positivity (<20% of tumour cells) or the absence of cyclin E immunoreactivity was observed in 105/142 (73.9%) in all cases. Cyclin E expression was correlated with tumour stage. A positive relationship between cyclin E expression and the two associated proliferating indices Ki-67 and PCNA, as well as with p53 and p27(Kip1) proteins expression was noted. Absence or focal positivity (<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%) of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour grade and stage. A positive relationship of its expression cyclin D1, cyclin E, p27 and pRb expression was observed. Absence or focal immunostaining (<20% of tumour cells) of p27 protein was detected in 55/141 (39%) in all cases. p27(Kip1) expression was correlated with tumour grade as well as with cyclins D1 and E. The prognostic significance of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and progression with both univariate (log rank test) and multivariate (Cox regression) methods of analysis showed no statistically significance differences. CONCLUSION: These findings suggest that the level of the cell cycle regulators studied does not seem to have a clinical value in terms of predicting the risk of early recurrence and progression. In addition the interrelationship probably means their contribution to the regulation of cell growth through different pathways in bladder carcinogenesis.     

p21, p53, and p27 Kip1 alterations in benign and malignant tumors of sinonasal epithelium.

OBJECTIVE: The goal of this study was to investigate alterations of cell cycle-related molecules, including p27, p21, and p53, in inverted papillomas (IPs) and squamous cell carcinomas (SCCs) of the sinonasal epithelium.Study design Sixteen IPs and 6 SCCs of the sinonasal epithelium, surgically resected at Istanbul Faculty of Medicine, Department of Otorhinolaryngology, from 1992 to 2000 were immunohistochemically investigated (p27, p21, and p53). RESULTS: A significant decrease in p27 nuclear staining was observed for SCCs of paranasal sinus compared with inverted papillomas (P = 0.0072). In SCCs there was no association between p27 expression and the presence of keratinization and tumor grade. p21 and p53 expressions were not associated with IPs (dysplastic and nondysplastic) and SCCs. CONCLUSION: Reduced levels of p27 expression correlate with increased cell proliferation in tumors of sinonasal region. Our findings indicate that p27 immunohistochemistry can be recommended to analyze the dysregulation of cell kinetics in these tumors.     

Correlation between tumor angiogenesis and invasiveness in thymic epithelial tumors

OBJECTIVE: Because it is difficult to predict the behavior of thymomas on the basis of morphology alone, other methods for determining tumor aggressiveness must be explored. This study investigated the correlation between angiogenic grade and invasiveness in thymic epithelial tumors. METHODS: Immunohistochemical studies of 46 surgically resected thymic epithelial tumors (18 noninvasive thymomas, 20 invasive thymomas, and 8 thymic carcinomas) were conducted. To highlight the microvessels, we used a specific monoclonal antibody against factor VIII. Expression of vascular endothelial growth factor and basic fibroblast growth factor was determined by using polyclonal antibodies. RESULTS: Mean microvessel density readings for noninvasive thymomas, invasive thymomas, and thymic carcinomas were 4.6 +/- 3.2, 12.4 +/- 7.5, and 34.4 +/- 16.7, respectively. Stages I, II, III, and IV of thymoma had microvessel density readings of 4.6 +/- 3.2, 8.5 +/- 4.3, 13.8 +/- 7.7, and 22.0 +/- 6.8, respectively. These findings suggest a significant correlation between microvessel density and tumor invasiveness. Vascular endothelial growth factor expression in noninvasive thymomas, invasive thymomas, and thymic carcinomas was present in 1 (5.6%) of 18, 11 (55.0%) of 20, and 5 (62.5%) of 8 patients, respectively, thereby indicating a distinct association between vascular endothelial growth factor expression and increased microvessel density. Basic fibroblast growth factor expression was present in only 8 patients. CONCLUSIONS: In patients with thymic epithelial tumors, there appears to be a significant correlation between tumor angiogenesis and invasiveness. Furthermore, our data suggests that this angiogenesis in thymic epithelial tumors might be, at least in part, dependent on vascular endothelial growth factor expression.     

Prognostic importance of histomorphologic subclassification for epithelial thymic tumors

Background: The prognostic importance of various clinical variables (age, sex, association with myasthenia gravis), staging according to Masaoka, histologic type according to the Marino/Kirchner/Müller-Hermelink (MKM-H) classification, and residual tumor category (R category) was evaluated in a retrospective analysis. Methods: Eighty-two patients with epithelial thymic tumors (ETTs) treated in the period 1969–1993 were evaluated, and archived specimens were histologically reclassified according to the classification of MKM-H. Results: Age, sex, and association with myasthenia gravis were of no prognostic importance. The R category is of significant prognostic importance, with 5- and 10-year survival rates of 93.6% and 87.3%, respectively, for R0 resections compared with 0% at 5 years for R1 and R2 resections (p<0.001). Staging (Masaoka) proved to be a prognostic factor (5-/10-year survival: stage I, 100%/90.9%; II, 95%/88.2%; III, 55.9%/46.6%; and IV, 10.8%/10.8%; p<0.001). Histologic typing according to MKM-H is also of significant prognostic importance (5/10 year survival: thymomas: medullary, 100%/100%; mixed, 100%/100%, predominantly cortical, 68.6%/68.6%; cortical, 65.8%/65.8%; thymic carcinomas: well-differentiated type, 62.3%/44.5%; thymic carcinomas other than well-differentiated type, 33.6%/26.9%; p<0.001). Multivariate analysis demonstrated that staging (p<0.001), R category (p<0.026), and MKM-H classification (p<0.028) have an independent impact on survival. Conclusions: Staging (Masaoka), R category, and histologic classification (MKM-H) are important independent prognostic factors for patients with epithelial thymic tumors. Complete (R0) surgical resections should be the ultimate goal in the clinical management of patients with epithelial thymic tumors.     

Cyclin-dependent kinase inhibitors,p16 and p27, demonstrate different expression patterns in thymoma and thymic carcinoma

Objectives

The role of cell cycle inhibitors in tumorigenesis has been proven in various neoplasms; however, their roles in thymic tumors are still unclear. We examined the expression of cell cycle inhibitors such as those of the Cip/Kip family (p21, p27, and p57) and the INK-4/ARF family (p16 and p14) in thymoma and thymic carcinoma.

Methods

Samples from 41 thymoma and 14 thymic carcinoma patients, and 34 normal thymic tissue samples were prepared for the study. Immunohistochemical analysis using antibodies to p21, p27, p57, p16, and p14 was carried out, and the positivity for these inhibitors in each group was estimated in terms of their subcellular location and percentage of cells showing positive staining.

Results

Nuclear p27 showed a stepwise decrease (p < 0.0001), and the cytoplasmic p27 showed a stepwise increase (p < 0.0001) in expression level with the increase in malignancy. p16 in both the nucleus and cytoplasm showed a stepwise increase (p < 0.0001) in expression level with the increase in malignancy. However, as for p21, p57, and p14, there was almost no nuclear or cytoplasmic expression in each group.

Conclusions

Our findings suggest that low nuclear and high cytoplasmic p27 expression levels, and high nuclear and cytoplasmic p16 expression levels may correlate with the increase in thymic malignancy.     

直肠癌P27基因表达及血清转化生长因子β1水平的变化

目的 探讨直肠癌中p27的表达和血清转化生长因子β1(TGF-β1)的水平。以及TGF-β1对p27的调控关系。方法 对37例直肠癌、22例直肠腺瘤和19例正常对照者用免疫组化二步法检测其p27的表达情况。用酶联免疫吸附法(ELISA)测定血清TGF-β1水平。结果 p27在正常直肠组织和直肠腺瘤组织中呈高表达。其表达阳性率分别为89．47％和90．91％，阳性表达定位于细胞核；直肠癌组织中p27表达阳性率降为64．87％，与前两者比较，差异有统计学意义(P=0．025)，且伴有p27细胞浆表达者占45．83％。血清TGF-β1在正常对照组的表达阳性率为21．05％，直肠腺瘤组为27．27％，而直肠癌组则升至51．35％(P=0．045)。p27的表达与直肠癌的分化程度、淋巴结转移和浸润深度有关；血清TGF-β1表达水平与直肠癌的淋巴结转移、浸润深度和CEA水平有关。血清TGF-β1阴性组中p27表达阳性率为88．89％，血清TGF-β1阳性组中p27表达阳性率降为42．11％。差异有显著性意义(Mantel-Haenszel χ^2=6．755，P=0．009)。结论 p27对于判断直肠癌的恶性程度和预后有指导作用，血清TGF-β1可作为直肠癌的辅助诊断指标，TGF-β1可下调直肠癌中p27的蛋白表达。     

肝细胞肝癌中p27KIP1基因的表达及意义

目的 探讨p27^KIP1与原发性肝细胞癌(HCC)发生、发展的关系。方法 应用SASC(链霉 素亲和康—生物康复合物)免疫组化染色和mRNA原位杂交方法，对52例肝细胞肝癌中p27^KIP1蛋白和mRNA的表达进行了检测。结果 p27^KIP1基因的表达主要位于肝或肝癌细胞的细胞核中，呈纫颗粒状分布。p27^KIP1蛋白在癌旁肝组织中的阳性细胞指数为(10．7士7．6)％，明显高于癌组织的(1．5士o．9)％，并且p27^KIP1蛋白表达的阳性细胞指数与HCC细胞的分化程度呈正相关。p27^KIP1mRNA杂交阳性物呈蓝色纫颗粒状，主要位于肝或肝癌细胞的细胞核和细胞浆中，mRNA阳性的细胞分布更广泛，但在癌旁肝组织和不同分化程度的HCC组织中，p27^KIP1mRNA的阳性细胞指数差异无显著性意义。结论p27^KIP1蛋白与HCC的发生及细胞分级有关。     

1 alpha,25-Dihydroxyvitamin D3 receptors in human thymic and tonsillar lymphocytes

In vitro activated human peripheral blood lymphocytes possess the receptor protein for 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). In the present study we have examined whether activated lymphocytes that occur in vivo in human thymuses and tonsils also possess receptors for 1,25(OH)2D3. Freshly isolated lymphocyte preparations, from five separate surgical specimens of thymus and tonsil, were depleted of monocytes and examined, before and after fractionation on a density gradient of Percoll, for [3H] 1,25(OH)2D3 binding by means of sucrose density gradient sedimentation, by saturation analysis of the binding, and by DNA-cellulose chromatography. The state of activation of the lymphocyte preparations was determined using [3H] thymidine incorporation, DNA and RNA quantitation (using acridine orange), and by determining the presence or absence of markers of activation (interleukin-2 receptor, transferrin receptor, and HLA-DR molecules). In both the thymic and the tonsillar lymphocyte preparations we detected a 1,25(OH)2D3-binding molecule possessing sedimentation coefficient of 3.3 S and dissociation constant of 10(-10) M as well as DNA binding capability. In thymic lymphocytes, the 1,25(OH)2D3 receptor concentration correlated positively with the number of lymphocytes expressing the transferrin receptor (r = 0.84; p less than 0.05). In addition, in both thymic and tonsillar lymphocytes the concentration of 1,25(OH)2D3 receptors correlated positively with the number of cells in the G1a phase of the cell cycle (r = 0.79, p less than 0.01, and r = 0.88, p less than 0.001 for thymic and tonsillar lymphocytes, respectively). In contrast, the 1,25(OH)2D3 receptor concentration in these preparations did not correlate with the rate of cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)