胃癌p53表达与其病理组织学和预后的关系

目的探讨不同部位胃癌的ｐ５３表达与其预后的相关性。方法采用免疫组化的方法对１７０例贲门癌和胃窦癌的ｐ５３表达及病理组织学和预后进行研究。结果在１７０例胃癌中ｐ５３阳性表达率为２８８％,其中胃底贲门癌的ｐ５３阳性表达率高于胃窦癌（３８８％∶２００％,Ｐ＜０．０５）。ｐ５３阳性组与ｐ５３阴性组的５年生存率无显著性差异（Ｐ＞０．０５）。ｐ５３蛋白表达不仅与５年生存率无关,而且与早期或进展期胃癌、胃癌的部位、有无淋巴结转移、有无局部淋巴管与血管浸润等无关。结论本研究结果表明,胃底贲门癌的ｐ５３免疫蛋白表达较胃窦癌高,但ｐ５３蛋白核染色不能作为判断胃癌预后的指标或参数。     

p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer.Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis.Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression.Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.     

FBXO43在胃癌中的表达及其生物学功能与作用机制

背景与目的：F-BOX蛋白（FBP）家族成员F-box only protein 43 (FBXO43）在肝癌和结直肠癌等消化系统肿瘤中高表达,促进肿瘤恶性进展,且研究显示,FBXO43促进p53降解,发挥促瘤功能。为此本研究进一步探讨FBXO43在胃癌中的表达及其在胃癌恶性进展中的功能与相关机制。方法：基于TCGA、GTEx和Kaplan-Meier Plotter等在线数据库,分析FBXO43在胃癌组织中的表达及其与胃癌患者预后的相关性。用Western blot和qPCR检测FBXO43在胃癌细胞与正常胃黏膜上皮细胞中的表达水平;用免疫组化检测在胃癌组织与癌旁组织中FBXO43的蛋白水平。利用脂质体转染特异性靶向FBXO43和p53的小分子干扰RNA分子（siFBXO43和sip53）,分别或同时敲低HGC27和MGC803细胞中的FBXO43和p53的表达,利用CCK8、平板克隆形成、Transwell侵袭和迁移等实验,检测细胞生长、增殖、迁移和侵袭能力的影响;利用免疫共沉淀（Co-IP）检测FBXO43和p53的相互作用情况,以及敲低FBXO43后,p53的总泛素化水平。结果...     

p53、bcl-2和nm23基因在胃癌组织中的表达及其临床意义

目的　研究胃癌组织中bcl 2、p5 3和nm2 3基因的表达及其与临床病理的关系 ,探讨bcl 2、p5 3和nm2 3基因与胃癌生物学行为的相关性。方法　采用免疫组化方法对 80例胃癌组织、3 7例不典型增生癌旁组织及 2 0例正常胃粘膜组织中的bcl 2、p5 3和nm 2 3基因的表达情况进行检测。 结果　bcl 2蛋白在胃癌癌旁轻、中、重度不典型增生组织中的表达阳性率分别为 7.1%、18.1%和 2 5 .0 % ,其在各组间表达的差异无统计学意义 (P>0 .0 5 ) ,bcl 2蛋白在高分化胃癌组织中的表达阳性率为 78.2 % ,明显高于在低分化胃癌组织中的表达 (4 8.5 % ,P<0 .0 5 )。p5 3在高分化胃癌组织中的表达阳性率为 72 .5 % ,明显低于低分化胃癌组织的 86.2 % (P<0 .0 5 )。nm 2 3在高分化胃癌组织中的表达阳性率为84.3 % ,明显高于低分化胃癌组织的 17.2 % (P<0 .0 5 )。伴有淋巴结转移的胃癌组织中nm 2 3的表达阳性率为 5 4.5 % ,低于无淋巴结转移者的表达阳性率 (85 .7% ,P<0 .0 5 )。p5 3与bcl 2在胃癌组织中的表达呈明显负相关。结论　bcl 2、p5 3和nm 2 3的表达与胃癌细胞的分化程度密切相关 ,对患者预后有重要参考价值。     

Prognostic Significance of p53 and Ki67 Proteins Expression in Greek Gastric Cancer Patients

Aim: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. Materials and methods: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. Results: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival.

Conclusions: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.     

Detection of Bone Marrow Micrometastasis in Gastric Cancer Patients by Immunomagnetic Separation

Background:Micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients after surgery. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of gastric cancer patients.Methods:Bone marrow and peripheral blood samples were obtained from 53 gastric cancer patients at the time of surgery. These samples were enriched by immunomagnetic separation and immunostained with an anti-cytokeratin antibody. Expression of vascular endothelial growth factor and erbB-2/HER2 was examined in the primary tumors.Results:Cytokeratin-positive cancer cells were observed in the bone marrow of 16 (30%) of 53 patients. Among them, two patients also had cancer cells in the peripheral blood. The presence of bone marrow micrometastasis was correlated with the depth of invasion and lymph node metastasis but was not associated with peritoneal dissemination. Detection of bone marrow micrometastasis was not correlated with vascular endothelial growth factor or HER2 expression in the primary tumors. Four patients with micrometastasis had recurrence in the liver or lungs, but this did not occur in patients without micrometastasis.Conclusions:Detection of cancer cells in the bone marrow might be an indicator of postoperative hematogenous metastasis in gastric cancer patients.     

突变型p53与Nampt在胃癌组织中的表达及其与预后的关系

目的：探讨突变型p53（mutp53）和尼克酰胺磷酸核糖转移酶（Nampt）在胃癌组织中的表达及其对患者预后的影响。方法：用免疫组化法检测68例胃癌患者胃癌组织及癌旁正常胃黏膜组织中p53（免疫组化检测到的p53主要为mutp53）与Nampt的表达,分析mutp53与Nampt表达与患者临床病理因素及预后的关系。 结果：胃癌组织中mutp53与Nampt的阳性表达率均明显高于癌旁正常胃黏膜组织（均P<0.05）;mutp53的高表达与肿瘤大小、浸润深度、淋巴结转移及TNM分期有关,而Nampt的高表达与肿瘤浸润深度、淋巴结转移及TNM分期有关（均P<0.05）。胃癌组织中,p53表达与Nampt表达呈明显正相关（r=0.982,P<0.05）。p53阳性表达患者的中位生存期明显短于阴性表达患者,且在p53阳性表达患者中,Nampt同时阳性患者的中位生存期明显短于Nampt阴性患者（均P<0.05）。结论：mutp53与Nampt的表达均与胃癌的恶性生物学行为相关,且两者存在一定的关联性,同时高表达患者预后差。

     

Association between sucrase-isomaltase and p53 expression in colorectal cancer

Background: Sucrase-isomaltase (SI) is a tissue-based phenotypic marker that is an independent prognostic factor in colorectal cancer (CRC). DF3 and galectin 3 are two other tissue-based markers that are upregulated during neoplastic transformation. Because p53 mutations are acquired during neoplastic progression, we reasoned that alterations in SI and p53 may be associated despite an apparent lack of biological interaction. Methods: Paraffin sections from 183 patients who underwent surgery at New England Deaconess Hospital (NEDH) between 1965 and 1977 were analyzed first by immunohistochemistry (IHC) for the expression of the markers SI, DF3, and galectin 3, which were scored as absent or present. Paraffin sections from a second group of 59 patients who underwent surgery at NEDH between 1985 and 1992 were analyzed by IHC for the expression of p53 as well as SI, DF3, and galectin 3. p53 nuclear staining was scored as absent or present. Previous work has shown that p53 is mutated in all cells with nuclear staining and in 10% of tumors that are unstained. Results: SI expression was not associated with the expression of either DF3 or galectin 3, and neither DF3 nor galectin 3 were prognostic factors in CRC. None of the phenotypic markers were associated with any of the clinicopathologic variables. However, 21 of 24 p53-positive cases (88%) expressed SI, whereas 15 of 35 p53-negative cases (43%) were also SI negative (p=0.02, Fisher exact test). p53 expression was not associated with expression of DF3 or galectin 3. Conclusions: SI expression and p53 mutation are associated significantly in CRC. Although the mechanism underlying such an association is presently unknown, the association may define a subset of patients with a worse prognosis.Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

Clinicopathologic significance of Her-2 and P53 expressions in gastric cancer

BackgroundTo detect the expression of HER-2 and P53 patients with gastric cancer and to analyze their correlation.MethodsA total of 249 gastric cancer patients with complete clinical data who received surgical treatment from China–Japan Union Hospital of Jilin University were selected. The expression of Her-2 and P53 were detected by immunohistochemistry using the streptavidin-biotin-peroxidase method. The correlations between HER-2 and P53 in gastric cancer were analyzed.ResultsThe positive rate of Her-2 and P53 expression was 37.3% (93/249) and 100% in all the specimens, respectively. The intensity of Her-2 expression was significantly different in patients with different degrees of gastric cancer cell differentiation (P = 0.012). Meanwhile, the expression of her-2 was closely related to whether the pathological type of gastric cancer was a signet-ring cell carcinoma (P = 0.022). Different percentage of positive P53 expression was closely related to the grade of tumor differentiation (P = 0.035) and positive Ki67 expression (P = 0.001). There was a significant positive correlation between HER-2 and P53 expression in gastric cancer (P = 0.003). These findings suggest that HER-2 and P53 have synergistic effects in gastric cancer.ConclusionHer-2 and P53 are important markers for invasion and metastasis of gastric cancer. Combined detection of P53 and Her-2 expression in gastric cancer tissue can be used to assess prognosis and screen cancer patients at high risk of metastasis.     

Expression of p53 and RB Proteins in Squamous Cell Carcinoma of the Esophagus: Their Relationship With Clinicopathologic Characteristics

Background: Cancer of the esophagus is one of the most malignant tumors and has a poor prognosis. The p53 and retinoblastoma (RB) genes are involved in the regulation of cell population by suppressing cell proliferative activity. Our goal was to clarify whether expression of p53 and RB genes could be prognostic factors in squamous cell carcinoma of the esophagus.Methods: Tumor samples taken from 73 patients undergoing subtotal esophagectomy were immunohistochemically stained for the p53 and RB genes. An image analyzer was used for quantitative assessment of the staining, and clinicopathologic characteristics of those patients were investigated.Results: Patients in whom p53 expression was high had greater tumor diameter, deeper tumor invasion, and worse prognosis compared with patients in whom p53 expression was low. Patients in whom RB expression was low had a higher incidence of lymph node metastasis and more advanced disease than did those in whom RB expression was high. The combination of p53 and RB expression revealed that the cases with high p53 and low RB expression had significantly worse survival rates and deeper tumor invasion compared with other groups. In various clinicopathologic parameters, (e.g., age, sex, tumor-diameter, tumor type, location, differentiation, TNM classification,TNM stage) tumor type, tumor size, depth of invasion, lymph node involvement, distant metastasis, and combined p53 and RB expression showed significant differences in survival by univariate analysis. Among those six variables, only lymph node involvement showed an independent prognostic factor for survival (P = .0055) by multivariate analysis.Conclusions: The combination of p53 and RB expression is not a prognostic indicator in the surgical treatment of esophageal cancer.     

Analysis of the Survival Period in Resectable Stage IV Gastric Cancer

Background: Patients with stage IV gastric cancer usually have a poor prognosis, but some patients with resectable cancer survive for more than 5 years. We aimed to study the correlation of protein expression and survival in resectable stage IV gastric cancer.Patients and Methods: Tissue samples of 42 patients with resectable stage IV gastric cancer were stained immunohistochemically for the mutant p53 protein and heat shock protein-27 (hsp27). The correlation between protein expression and clinicopathological factors was investigated. Furthermore, prognostic value of each factor was analyzed.Results: Univariate analysis showed that pN factors (Japanese classification, P = .028; International Union Against Cancer classification, P = .024), blood vessel invasion (P = .043), hsp27 overexpression (P = .019), and the index of p53 and hsp27 overexpression (P = .0026) had a prognostic influence. Only Lauren classification, however, revealed the prognostic influence in multivariate analysis (P = .046).Conclusions: These results suggest that immunostaining of tumor specimens for p53 and hsp27 and clinicopathological analysis may help predict the survival of patients with resectable stage IV gastric cancer.     

The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer

PurposeTo investigate the association between p53 expression in tumor cells and intratumoral macrophage infiltration in muscle-invasive urinary bladder cancer (MIBC) in relation to clinical and pathological variables and outcomes after radical cystectomy.MethodsTumor specimens of the primary tumor from patients treated with radical cystectomy for MIBC were immunostained with the M2-macrophage-specific marker CD163 and the cell cycle protein p53. The expression of these markers was analyzed in relation to patients´ and tumor characteristics and outcome.ResultsOut of 100 patients with urinary bladder cancer (UBC) pathological stage T1-4 N0-3 M0, 77% were men. The patients had a median age of 69 years and 80% had nonorgan-confined tumors (pT3-4). Lymph node metastasis was found in 42 (42%) of all patients. P53-positive expressions were found in 63 (63%) patients. Strong macrophage infiltration in the tumor microenvironment was shown in 74 (74%) patients. Combinations of CD163/p53 status were as follows: CD163+/p53+, 50%; CD163+/p53-, 24%; CD163-/p53+, 13%; and CD163-/p53-, 13%. Patients with CD163+/P53+ had higher proportions of organ-confined tumors.ConclusionsIn the present series of patients with MIBC treated with cystectomy, we found that high CD163+ macrophage infiltration in the tumor micro-environment often was combined with p53+ cancer cells. This simultaneous expression of p53 by tumor cells and increased infiltration of M2-macrophages in the tumor microenvironment was associated with improved CSS, which might indicate a possible protective effect of M2 macrophages in p53+ tumors. Further investigations are needed to explore the biological relation between mutational burden and immune profile in MIBC.     

胃癌腹膜转移与相关因素表达及预后的关系

目的 探讨进展期胃癌腹膜转移的分子生物学特征及临床病理特征与预后的关系,寻找一种能早期诊断腹膜转移的临床可行方法.方法 对193例胃癌患者的分子生物学特征、临床特征及预后进行单因素及相关因素分析,并进行风险评估.结果 年龄越低,胃癌腹膜转移的越早;ICAM-1和MMP-2在胃癌发生腹膜转移的患者中高表达;TIMP-1,p53在胃癌发生腹膜转移的患者中表达降低.结论 测定ICAM-1,MMP-2,TIMP-1,p53能较好的预测是否发生转移及其预后;血清ICAM-1,TIMP-1,MMP-2,p53作为术前判断胃癌是否发生转移提供了一种可行的方法.     

联合评估survivin和p53在胃癌组织中表达的临床意义及对预后的影响

目的 研究胃癌原发灶中survivin和p53的表达与临床病理特征,恶性潜能及预后的影响。方法 免疫组化法检测125例行根治切除胃癌组织中survivin和p53表达情况,采用单因素和多因素分析比较survivin和p53表达及其共同表达与临床病理特征和预后关系。结果 survivin和p53表达阳性率各自为57．6％（72例／125例）和59．2％（74例／125例）。survivin阳性表达率在弥漫型和组织分化差（均P〈0．01）、肿瘤浸润更深、有淋巴结转移、淋巴管浸润及进展期（P〈0．05）胃癌组织中显著增高。p53表达与淋巴结转移和淋巴管浸润（P〈0．037）相关。单因素分析显示,survivin和p53表达阳性分别与5年生存率有关（P=0．0050和P=0．0025）。多因素分析显示,survivin和p53共同表达患者预后更差（P=0．001）。结论 survivin和p53在胃癌组织中均有较高的表达率,survivin阳性表达和p53阳性表达分别提示预后不良,survivin和p53共同表达为胃癌根治术后独立的预后因子。     

Clinicopathologic and Immunohistochemistry Characterization of Synchronous Multiple Primary Gastric Adenocarcinoma

The aim of this investigation was to evaluate clinicopathologic and immunohistochemical characteristics of synchronous primary gastric adenocarcinomas. Immunohistochemistry for p53 (suppressor pathway) and for hMLH1, hMSH2, and hMSH6 (mutator pathway) was performed using ABC-technique amplification by biotinylated tyramide. Synchronous primary gastric adenocarcinomas were detected in 19/553 (3.43%) of the patients. The tumors were localized in distal stomach in 22, body in 14, and proximal in five. There was a predominance of intestinal type in the group of synchronic tumors compared to the solitary lesions, 73.2 vs 37.3%, p = 0.001. Synchronous neoplasias were diagnosed in earlier stage than solitary neoplasias, T1-T2 = 60.9% vs T1-T2 = 28.4%, p = 0.0001; and N0 = 68.4% vs N0 = 26.2%, p = 0.001. p53 was detected in 52.6% of the patients with synchronous tumors. Altered hMLH1 immunoexpression occurred in 26.3% of the patients and hMSH6 in 5.3%. hMSH2 immunoreactivity was positive in all tumors. p53 was solely detected in 17 tumors, while hMLH1 was altered in 10/24 negative p53 tumors, p = 0.01. Synchronous gastric adenocarcinomas presented higher frequency of intestinal type and early gastric cancer in comparison to solitary gastric cancer. Two routes of carcinogenesis, mutator, and suppressor appear to be involved independently in the development of synchronous tumors.     

Lymph node metastasis as a significant prognostic factor in early gastric cancer: Analysis of 1,136 early gastric cancers

Background: Gastric cancer is the most frquent cancer and the leading cause of death from cancer in Korea. Early gastric cancer has been defined as a gastric carcinoma confined to mucosa or submucosa, regardless of lymph node status, and has an excellent prognosis with a >90% 5-year survival rate. From 1974 to 1992, we encountered 7,606 cases of gastric cancer and performed 6,928 gastric resections. Among them, 1,136 cases were early gastric cancer (14.9% of all gastric cancer cases and 16.4% of resected gastric cancer cases). Methods: A retrospective analysis of 1,136 cases of early gastric cancer was performed to evaluate the prognostic significance of clinicopathologic features (sex, age, tumor location, gross type, histologic type, depth of invasion, status of lymph node metastasis, resection type). Lymph node metastasis was classified into three groups: N(n=0) for no lymph node metastasis; N(n=1–3) for one to three lymph node metastases; and N(n>3) for more than three lymph node metastases. All patients received radical total or subtotal gastrectomy with lymph node dissection. Results: In univariate and multivariate analysis of these nine factors, the only statistically significant prognostic factor was regional lymph node metastasis (p<0.001). The others had no statistically significant association with prognosis. Lymph node metastasis was present in 178 cases (15.7%). The factors associated with the lymph node metastasis were depth of invasion and gross type [protruding type (e.g., types I, IIa)]. One hundred twenty-five of these patients had one to three lymph node metastases, and 53 cases had more than three lymph node metastases. The difference in 5-year survival rates among these groups was statistically significant: 94.5% for N(n=0), 88.3% for N(n=1–3), and 77.3% for N(n>3). Conclusion: We propose that for early gastric cancer, lymph node dissection is necessary in addition to gastric resection, at least in patients with a high risk of lymph node metastasis.     

Expression of p53 product in Chinese human bladder carcinoma

Summary Expression of p53 protein was examined in 67 cases of primary transitional cell carcinoma of the bladder and 6 normal controls using an immunohistochemical method on paraffin sections. Positive nuclear staining for p53 in malignant cells was found in 34 (51%) of the 67 cancer patients; no positive staining for p53 was detected in any of the normal controls or in the benign cells, including stromal and inflammatory cells, within the tumor tissue. There were 8 positive cases (33%) in 24 grade G1 tumors, 12 (48%) in 25 G2 tumors and 14 (78%) in 18 G3 tumors. p53 protein was detected positively in 14 (36%) of 39 superficial tumors (Tis-T1) and in 20 (71%) of 28 invasive tumors (T2–T4). Thus, positive staining for p53 was found more frequently in poorly differentiated tumors (chi-squared test: G3/G1+G2P<0.01) and in invasive tumors (chi-squared test: T2–T4/Tis-T1P<0.01). Expression of p53 was also closely associated with recurrence of tumors. Alterations in p53 expression may be of prognostic value in cases of bladder transitional cell carcinoma.     

Prognostic prediction of the immunohistochemical expression of p53 and p16 in resected non-small cell lung cancer.

OBJECTIVE: p53 and p16(INK4) are the common and important tumor suppressor genes. Aberrant expression of p53 or p16 protein has been reported in various malignancies including lung cancer. Our aim was to investigate the association of p53 and p16 expression in resected non-small cell lung carcinoma (NSCLC) and evaluated their correlation with clinocopathologic features and survival. METHODS: p16 and p53 expression were detected by immunohistochemical analysis of 90 paraffin specimens of resected NSCLC, including 35 squamous cell carcinoma, 47 adenocarcinoma, and eight large cell carcinoma, between stages I and IV. The immunohistochemical study was performed using the labeled streptavidine-biotin method with anti-p53 and anti-p16 monoclonal antibodies. RESULTS: Fifty-two (57.8%) and 36 (40%) of 90 patients revealed aberrant immunostaining for p53 (p53+) and p16 (p16+), respectively. While 19 cases (21.1%) showed abnormal immunoreactivity for both p16 and p53. (p53+/p16+). There was no correlation of p53 or p16 expression with the clinicopathologic features. The Kaplan-Meier survival analysis demonstrated that patients with p16+, p53+, late stages, and nodal or distal metastasis had poor survival status (P = 0.006, 0.013, <0.001, <0.001 and 0.018, respectively). Further analysis demonstrated that p53 status was a significant prognostic factor in stage I NSCLCs (P < 0.001), and p16 status in stage I and II NSCLCs (P < 0.001, P = 0.003, respectively). Furthermore, patients whose tumors were both p53 and p16 aberrant expression had worse outcome compared with those whose tumors were both normal expression of p53 and p16 (5-year survival rate: 5 vs. 76%, P < 0.001). In Cox's regression model, the aberrant expression of p16, p53, advanced stages and combined aberrant expression of p53/p16 survived for a significant shorter period. CONCLUSIONS: The results indicated that aberrant expression of p16 and p53 are significant and independent, predictable prognostic factors for resected NSCLC, especially in early stage of NSCLCs. The worst prognosis was seen in patients whose tumors had both aberrant expression of p53 and p16. Further prospective trials may be aimed at confirming and validating these results.     

胃癌组织中p53蛋白表达的临床意义

目的：观察ｐ５３蛋表达通融作为判断胃癌病的预后指标,为该指标的合理应用提供科学依据。方法 利用免疫组化技术检测１７１例胃癌切除标本内ｐ５３蛋白的表达,分析ｐ５３蛋白表达与临床病理及承后之间的关系,探讨ｐ５３蛋白表达与传统ＴＮＭ分期在预后中的关系。结果 ４３．３％的胃癌组织有ｐ５３蛋白表达,弥漫型胃癌中的ｐ５３蛋白表达率高于肠型胃癌（Ｐ〈０．０５）;有ｐ５３蛋白表达的胃癌组织易于发生洒巴结转移（Ｐ〈     

Micropapillary urothelial carcinoma of urinary bladder displays immunophenotypic features of luminal and p53-like subtypes and is not a variant of adenocarcinoma

ObjectivesMicropapillary urothelial carcinoma of the urinary bladder (MPUC) is a rare variant of urothelial carcinoma which has aggressive clinical characteristics. The objective is to investigate the molecular subtypes of MPUC and the impact to the clinical outcome and determine whether MPUC represents a variant of adenocarcinoma.Materials and MethodsWe evaluated surrogate immunohistochemical markers of luminal, basal, and p53-like subtypes and correlated with prognosis and the expression of markers related to bladder adenocarcinoma and glandular differentiation in 56 cases of MPUC (10 cases of transurethral resection and 46 cases of radical cystectomy). Biomarker expression in co-existing conventional urothelial carcinoma was also analyzed. Cox regression analysis was performed to study the impact of molecular subtype on the clinical outcome.ResultsThirty-four cases (61%) met criteria for the luminal subtype. Twenty-two cases (39%) displayed a p53-like subtype. In contrast, 40/56 (71%) cases of coexisting conventional urothelial carcinoma were classified as luminal subtype and 16/56 (29%) cases were designated as p53-like subtype. There was no significant survival difference between luminal subtype and p53-like subtype. CDX2, villin, and cadherin 17 were negative in all cases. MUC1 was strongly and diffusely expressed in the stroma-facing surface of MPUC tumor cells in all the cases.ConclusionsOur findings suggest that MPUC possesses characteristics of luminal and p53-like subtypes, and does not harbor phenotypic features of the basal subtype. There is no significant difference in the prognosis between luminal and p53-like subtype MPUC. MPUC is not a variant of adenocarcinoma and does not represent a form of glandular differentiation, in contrast to other organ sites.