细胞周期素E和P53蛋白在胃癌组织中表达及预后意义

目的 :研究细胞周期素E(cyclinE)和P53蛋白在胃癌组织中的表达水平及其与生物学行为和对预后的作用。方法 :应用免疫组化方法检测 1 2 8例胃癌组织中cyclinE和P53蛋白表达水平。 结果 :本组 1 2 8例中 ,cyclinE蛋白阳性 57例 ,占 44 .5 % ;P53蛋白阳性 67例 ,占 52 .3 % ,P53 +/cyclinE +者 48例 ,占 37.5 %。胃癌组织中cyclinE和P53蛋白表达水平与肿瘤大小、浸润深度、局部淋巴结转移、脉管侵犯和远处转移均相关。单因素生存分析显示 ,cyclinE阳性表达组五年生存率 (5 .3 % )显著低于cyclinE表达阴性组 (36 .6 % ,P <0 .0 0 1 ) ,P53蛋白表达阳性的病例五年生存率 (7.8% )显著低于P53表达阴性的病例 (2 2 .6 % ,P <0 .0 0 1 ) ,cyclinE和P53均阳性的病例五年生存率 (2 .3 % ) ,明显低于其他组的病例 (2 7.3 % ,P <0 .0 0 5)。COX模型多因素分析显示 ,cyclinE蛋白表达水平是独立的预后指标 ,P53蛋白表达水平不能作为独立的预后指标。结论 :CyclinE在胃癌中表达具有一定的预后意义 ,P53蛋白在胃癌中表达与肿瘤的生物学行为有关     

p27和cyclin E蛋白表达与膀胱移行细胞癌生物学行为的关系

目的　探讨细胞周期蛋白p2 7和cyclinE表达与膀胱移行细胞癌生物学行为的关系。 方法　对 12 1例膀胱移行细胞癌进行组织病理学分级及分期 ,另取 10例正常膀胱组织作对照 ,采用免疫组织化学SABC法检测各例组织中 p2 7和cyclinE蛋白表达水平 ,并分析其表达与临床病理特征的关系。结果　p2 7和cyclinE蛋白阳性表达率分别为 42 .1% ( 5 1/12 1)和 3 4.7% ( 4 2 /12 1)。p2 7和cyclinE蛋白表达均与肿瘤的组织学分级显著相关 ,但与病理分期无关。p2 7蛋白与cyclinE蛋白表达呈负相关 (P<0 .0 5 )。p2 7阴性组中 ,cyclinE阳性患者 5年生存率低于cyclinE阴性者 (P <0 .0 5 ) ;p2 7阳性组中 ,cyclinE表达状况与患者 5年生存率无显著相关。结论　p2 7和cyclinE是评估膀胱移行细胞癌预后的有价值的指标     

粘膜内和粘膜下胃癌中Cyclin E表达的变化及意义

目的 探讨浸润加深时早期胃癌中Ｃｙｃｌｉｎ Ｅ的表达变化及其意义。 方法 用免疫组化法检测５７例粘膜层和５１例粘膜下层胃癌中Ｃｙｃｌｉｎ Ｅ及ｐ５３的表达。 结果 Ｃｙｃｌｉｎ Ｅ的强阳性率为粘膜内癌０％（０／５７）。粘膜下癌１８％（９／５１）（Ｐ〈０．０５）。在粘膜层胃癌：Ｃｙｃｌｉｎ Ｅ的阴性和低表达组间几乎所有的观察指标均无明显差异。在粘膜下层胃癌：Ｃｙｃｌｉｎ Ｅ高表达率在ｐ５３阳性者为３     

Low expression of p27(Kip1) is associated with tumor size and poor prognosis in patients with renal cell carcinoma

BACKGROUND: Proliferative activity in tumors depends on regulation of the cell cycle. p27(Kip1) (p27) plays a pivotal role as a negative regulator of the cell cycle. A decrease in p27 expression has been reported in many kinds of tumors, but little is known regarding p27 in patients with renal cell carcinoma (RCC). METHODS: Expression of p27 and the related cyclins (cyclin A, cyclin E, and cyclin D1) was examined immunohistochemically in 67 patients with of clear cell RCC. The Ki-67 labeling index (MIB-1 LI) and clinicopathologic parameters related to a poor prognosis also were analyzed. To determine their prognostic significance, univariate and multivariate survival analyses were performed. RESULTS: In tumors, there was considerable immunoreactivity for cyclin A, cyclin D1, and MIB-1, and the mean values for each were 1.08%, 16.1%, and 1.5%, respectively. Cyclin E expression was rare. The expression of p27 was correlated strongly with the expression of cyclin A (correlation coefficient, 0.432; P < 0.0004) and cyclin D1 (correlation coefficient, 0.476; P < 0.0004). Also, an inverse correlation was present between p27 expression and tumor size (P = 0.0377). In univariate analysis, the unfavorable prognostic factors were high TNM stage (P < 0.0001), large tumor size (P = 0.0016), high histologic grade (P = 0.0104), and low p27 expression (P < 0.0001). In multivariate analysis, high TNM stage (P = 0.0035) and low p27 expression (P = 0.0235) were independent prognostic factors for disease specific survival in patients with RCC. CONCLUSIONS: The results of this study suggest that low p27 expression may be a significant and independent, unfavorable prognostic factor in patients with renal cell carcinoma.     

Combined evaluation of expressions of cyclin E and p53 proteins as prognostic factors for patients with gastric cancer.

BACKGROUND: There is a lack of consistency regarding the prognostic value of cyclin E overexpression in gastric cancer (gastric cancer). Our aim was to report on this overexpression and to analyze its correlations with the clinicopathologic variables. Another aim was to examine if aberrant expression of both cyclin E and p53 might increase the malignant potential of gastric cancer. METHODS: Specimens from 89 patients with gastric cancer treated with "curative" intent were evaluated for cyclin E and p53 expressions using immunohistochemical method. The correlations between cyclin E overexpression alone or in combination with p53 expression and the patient's clinicopathologic variables were analyzed. RESULTS: Cyclin E overexpression and p53 expression were shown in 35 (39.3%) and 46 (51.7%) tumors, respectively. The incidence of cyclin E overexpression was significantly higher in deeply invasive cancers (P < 0.0001), in cancers with lymph node metastasis (P = 0.003), and in cancers with advanced stages (P < 0.0001). There were no significant correlations with other clinicopathologic variables. Patients in whom their tumors showed cyclin E overexpression alone or in combination with p53 survived less than patients with negative cyclin E tumors. Multivariate analysis revealed that combined cyclin E overexpression and p53 expression was significantly associated with poor survival after adjusting for other variables (hazard ratio, 3.12; P = 0.009). CONCLUSIONS: Cyclin E overexpression is a common event in gastric cancer. Gastric cancer with cyclin E overexpression exhibit increased aggressiveness in the presence of aberrant p53. The combination of cyclin E overexpression with the p53 expression in gastric cancer further distinguished a subgroup of patients with poor prognosis.     

p27~(Kip1)和细胞周期蛋白D1在胃癌中的表达及其预后意义

目的 :研究p2 7Kip1、细胞周期蛋白D1(cyclinD1)在胃癌组织中的表达水平以及与生物学行为的关系和对预后评价的意义。方法 :以免疫组化方法检测 92例胃癌组织中p2 7Kip1、cyclinD1蛋白的表达水平。结果 :本组 92例胃癌中 ,p2 7Kip1蛋白阳性 39例 ,占 42 .4% ;cyclinD1蛋白表达阳性 44例 ,占 47.8% ;胃癌组织中 ,p2 7Kip1蛋白水平与胃壁浸润深度、TNM分期、病理组织学分级、区域淋巴结转移均相关 (P <0 .0 5 ) ;cyclinD1蛋白表达与病理组织学分级负相关 (P <0 .0 5 ) ;p2 7Kip1与cyclinD1蛋白阳性表达显著相关 (P <0 .0 5 ) ;单变量生存分析结果 ,p2 7Kip1高表达组三年、五年生存率分别为 77.1%、5 7.8% ,明显高于低表达组的 33.7%、2 6 .3 % (P =0 .0 0 7) ,多变量分析显示p2 7Kip1是一个独立的预后指标 (P =0 .0 0 0 3)。结论 :p2 7Kip1可作为反映肿瘤恶性表型的指标 ,对胃癌预后具有一定的价值 ;cyclinD1是胃癌发生、发展过程中早期的分子事件 ;p2 7Kip1在胃癌进展中起着比cyclinD1更重要的作用。     

Cyclin E和p53的同时表达预测粘膜下层胃癌预后的作用

探讨Ｃｙｃｌｉｎ Ｅ和ｐ５３的同时表达对预测粘膜下层胃癌预后的作用。方法：用免疫组化法检测４８例粘膜下层胃癌中Ｃｙｃｌｉｎ Ｅ和ｐ５３的表达。结果：粘膜下层胃癌中Ｃｙｃｌｉｎ Ｅ阴性、阳性和强阳性组的ｐ５３表达率分别为１９％（５／２７）、４２％（５／１２）、８９％（８／９）（Ｐ〈０．０１）。同时表达的总发生率为２７％（１３／４８）。同时表达的发生率分别为：幽门部癌４６％（１１／２４）,侵入淋巴结者     

Expression of phosphorylated Akt (pAkt) in gastric carcinoma predicts prognosis and efficacy of chemotherapy

BACKGROUND: The Akt signaling pathway controls the survival and growth of human cancers. We investigated the expression of phosphorylated Akt (pAkt) in patients with gastric cancer. METHODS: The expression of pAkt was immunohistochemically examined in 140 gastric cancer patients who underwent a gastrectomy. The expression of pAkt was evaluated based on staining intensity, and staining was classified as negative or positive. We examined the expression of pAkt and its association with the clinicopathological findings, prognosis, depth of invasion, the expression of p53, and efficacy of oral fluorouracil chemotherapy after surgery. RESULTS: Expression of pAkt was positive in 81 (58%) patients and negative in 59 (42%) patients. There were no significant correlations between pAkt expression and the clinicopathological findings. The prognosis of patients with pAkt-negative tumors was superior to that of patients with pAkt-positive tumors, and the difference was significant for T3/T4 gastric cancer (P < 0.05). Among the patients with T3/T4 gastric cancer, postoperative oral fluorouracil treatment was effective in those who were pAkt-positive. Multivariate analysis revealed that pAkt expression and lymph node metastasis were independent prognostic factors. In 88 patients with T3 gastric carcinoma who had undergone curative surgery, in whom we studied the prognostic impact of a combined analysis of pAkt and p53 expression, patients with both pAkt- and p53-positive tumors showed a significantly poorer prognosis than patients with either or both pAkt- and p53-negative tumors (P < 0.05). CONCLUSION: Our results indicate that pAkt expression may be useful for predicting the prognosis and efficacy of fluorouracil treatment in patients with gastric cancer.     

cyclin D1、p53蛋白在胃癌组织中的表达

目的 研究cyclin D1、p53蛋白在胃癌组织中的表达及两者的相关性。方法 采用原位杂交技术及免疫组化技术，分别检测73例胃癌组织中cyclin D1 mRNA及p53蛋白的表达。结果 cyclin D1在胃癌组织及癌旁组织中的阳性表达率分别为54．79％（40／73）及28．77％（21／73），两者有显著性差异。cyclin D1 mRNA表达强度与肿瘤分化、浸润深度、淋巴结转移及病理分期无关（P＞0．05），p53蛋白在胃癌组织中的阳性表达率为32．88％（24／73），cyclin D1表达强度与p53表达无关（P＞0．05）。结论 cyclin D1及p53蛋白的过表达在胃癌的发生发展过程中均起重要作用。     

Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma

BACKGROUND: It has been reported that p53 regulates the G2-M checkpoint transition through cyclin B1, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The objective of the current study was to clarify the role of the cell cycle regulators, cyclin B1 and p53, in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Tissue samples from 71 patients with ESCC were included in the current study. Expression levels of cyclin B1 and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemistry. RESULTS: Several cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 20% of tumor cells were cyclin B1 positive in 38 patients (49.3%). Several clinicopathologic parameters, including macroscopic configuration (P < 0.01), pathologic tumor status (P < 0.05), pathologic lymph node status (P < 0.001), pathologic metastatic status (P < 0.01), tumor stage (P < 0.0001), and invasion of lymphatic vessels (P < 0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also were correlated with a poor prognosis in patients with ESCC in univariate analysis (P < 0.0001) and multivariate analysis (P = 0.0135). In contrast, p53 expression exhibited no significant correlation with the level of cyclin B1 expression and was not associated with prognostic parameters in patients with ESCC. CONCLUSIONS: These findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC.     

Expression of p27Kip1, cyclin E and E2F-1 in primary and metastatic tumors of gastric carcinoma.

The cell cycle is controlled by positive and negative regulators. Gene abnormalities and aberrant expressions of various cyclins/CDKs and CDK inhibitors may play a pivotal role in stomach carcinogenesis. To clarify the role of cyclin E, CDK inhibitor p27Kip1 and their target molecule, E2F-1 in tumor metastasis, we examined immunohistochemically the expression of cyclin E, p27Kip1 and E2F-1 in 23 gastric carcinomas and metastatic tumors of the lymph node. Most of gastric carcinomas with lymph node metastasis showed reduced p27Kip1 expression. p27Kip1 was negative in 39% (9/23) of primary tumors, while it was so in 52% (12/23) of lymph node metastases. By comparison of p27Kip1 expression in primary and metastatic tumors in individual cases, metastatic tumor cells in the lymph nodes were expressed at weaker levels than in those in primary tumors in 43% (10/23) of the cases. On the other hand, over 70% (17/23) and 50% (12/23) of the cases expressed cyclin E and E2F-1 at nearly the same levels in both primary tumor and lymph node metastasis, respectively. These results suggest that tumor cells with reduced p27Kip1 expression may selectively metastasize to lymph node or distant organs.     

Cyclin E expression in breast cancer correlates with negative steroid receptor status, HER2 expression, tumor grade and proliferation

The main objective of this retrospective study was to investigate relations between cyclin E and pathoclinical factors in patients with operable breast cancer. Expression of cyclin E was analyzed by immunohistochemistry in specimens of invasive ductal breast cancer tissue obtained from 189 women during radical mastectomy. Overall, 110 tumor samples were regarded to be cyclin E positive. Cyclin E expression was more often seen in tumors with: negative steroid receptor status (p<0.0001), higher proliferative index (p=0.0014), higher tumor grade (p=0.0017), and presence of HER2 (p=0.0171). With a median follow-up of 58 months, expression of cyclin E together with negative steroid receptor status determined poor prognosis with a 5-year cancer-specific survival rate of 58%. It differed significantly from a survival curve of cyclin E negative and steroid receptor positive patients (87%, p=0.0005). No significant difference was observed in comparison with survival of cyclin E positive and steroid receptor positive patients (68%, p=0.221). We demonstrated that cyclin E expression in breast cancer cells was associated with negative steroid receptor status, HER2 presence, higher tumor grade and higher proliferation index. Expression of cyclin E together with lack of steroid receptors determined poor prognosis.     

滑膜肉瘤组织中p27和cyclin E的表达及其临床意义

目的：探讨滑膜肉瘤组织中p27蛋白和cyclin E表达与临床病理指标的关系及判断预后的价值。方法：为46例滑膜肉瘤标本及10例正常滑膜组织的存档蜡块．应用免疫组化法观察p27蛋白和eyclin E的表达情况，并进行对比分析和相关性研究。结果：46例滑膜肉瘤组织中p27蛋白的阳性率为19．6％（9／46），正常滑膜组织中为90％（9／10），两者差异有统计学意义，P=0．01。p27蛋白表达与组织学分级有关，P=0．01；与性别、临床分期和组织学类型无关，P〉0．05。p27蛋白低表达者的5年生存率明显低于高表达者．P=0．01。eyclin E在滑膜肉瘤和正常滑膜组织中的表达差异有统计学意义，P=0．00；cyclin E的过表达在滑膜肉瘤的5年生存率组间差异有统计学意义，P=0．00。结论：p27低表达和cyclin E过表达与滑膜肉瘤的发生有关，是其预后差的有意义指标。联合检测p27和cyclin E表达对判断滑膜肉瘤的预后更有价值。     

Prognostic implication of cyclin E expression and its relationship with cyclin D1 and p27Kip1 expression on tissue microarrays of node negative breast cancer

BACKGROUND AND OBJECTIVES: Altered expression of cell-cycle regulators is prevalent in clinical breast cancer. This study was performed to analyze the impact of cyclin E expression to the outcome of breast cancer together with cyclin D1 and p27Kip1. METHODS: The correlation between cyclin D1/E and p27Kip1 expression was analyzed in tissue arrays of 175 node-negative breast cancers treated by the same chemotherapy composed of fluorouracil, cyclophosphamide, and methotrexate. Data from the immunohistochemical assays of three molecules were correlated and were analyzed with clinical outcome of the patients. RESULTS: Cyclin E expression was observed in 48 (27.4%) of 175 breast carcinomas. Cyclin E expression was significantly increased in young age patients and poorly differentiate tumors. Expression of cyclin E was significantly increased in cyclin D1 expressing tumors (P = 0.034). p27Kip1 expression was preserved above the 50% level in 87 tumors (49.7%) and was inversely correlated with cyclin E expression (P = 0.042). Ki67 labeling index was significantly increased in cyclin E-expressing tumors (P = 0.033) and was inversely related with p27Kip1 expression. In multivariate survival analysis, cyclin E expression was significant for the prediction of poor survival of the patients. CONCLUSIONS: Cyclin E expression was associated with poor prognosis and intimately correlated with the expression of cyclin D1 and p27Kip1. Integration of TMA technology allowed a high-throughput analysis for correlating molecular in situ findings with clinico-pathologic information.     

CD44v6、p27蛋白在大肠腺癌组织中表达的意义

目的探讨大肠腺癌组织中CD44v6、p27蛋白表达的意义.方法应用免疫组化S-P法检测大肠腺癌中CD44v6、p27蛋白表达.结果60例大肠腺癌中CD44v6、p27蛋白表达总阳性率分别为57%(34/60)、22%(1 3/60);两者阳性表达与大肠癌组织分化程度及浸润深度无明显相关性(P＞0.05),而与淋巴结转移及预后显著相关(P＜0.05);CD44v6阳性表达与大肠癌淋巴结转移呈正相关,与预后呈负相关,p27阳性表达与之相反.结论CD44v6、p27蛋白表达与大肠腺癌转移及预后相关,联合检测CD44v6、p27蛋白表达水平,对判断大肠癌恶性程度、复发转移潜能,评估患者预后及术后选择合理治疗方案有一定参考价值.     

Expression of cyclin D1 but not of cyclin E is an indicator of poor prognosis in small adenocarcinomas of the lung

We investigated the significance of cyclin D1 and cyclin E expression in resected tumors on the survival of patients with small adenocarcinomas of the lung. Seventy-two patients with resected tumors <2 cm in diameter and of pathological stage I were entered into the study. There were 29 males and 43 females, with a median age of 64 years (range 26-83 years). The patients underwent curative surgical resection for lung cancer between July 1992 and November 1999. The resected tumors were subjected to immunostaining for cyclin D1 and cyclin E expression. Twenty-six patients had tumors with >20% cyclin D1-positive cells, but only 1 patient had a tumor with >20% cyclin E-positive cells. When the survival of 72 patients was compared in relation to their oncogene expression, the overall survival of patients with positive expression of cyclin D1 was significantly worse than that of individuals whose tumors had negative expression of the gene (log-rank test p=0.0049). Increased expression of cyclin D1 but not of cyclin E is an indicator of poor prognosis in patients with small adenocarcinomas of the lung.     

5个免疫组化指标预测胃癌预后的意义

 目的　探讨微血管数和cyclin E、p53、CD44s、CD44v6的表达分别预测胃癌预后的作用。方法　以免疫组化法检测了95例胃癌的上述5指标,并同时检测了临床病理特征,然后研究了各个因素分别与预后和淋巴、静脉侵润的关系。结果　微血管数和cyclin E表达显著影响胃癌的预后。p53、CD44s、CD44v6的表达不显著影响预后。微血管数是显著独立的预后因素。微血管每增1支,淋巴管浸润的相对危险度都为增前的1.0314倍(P<0.05)。p53阳性癌淋巴结转移的相对危险度是阴性者的2.2403倍(P<0.05)。5个指标的过度表达或增高未使胃癌浸润静脉的相对危险度显著增高。结论　在胃癌中,微血管数是预测预后的重要指标,cyclin E表达也有一定预测作用,而p53、CD44s、CD44v6的表达无预后判断意义。     

流式细胞术对食管癌组织中四种细胞周期调控蛋白的定量检测及意义

目的 探讨细胞周期调控蛋白cyclin E、cyclin D1、CDK4和D27在食管癌的表达及其与食管癌的分化和淋巴结转移的关系。方法 采用流式细胞术对65例食管鳞状细胞癌组织中cyclin E、cyclin D1、CDK4和p27的表达强弱进仃定量检测,结果 用荧光指数F1表示。结果 cyclin E、cyclin D1和CDK4在低分化型鳞癌的表达量显著高于分化型鳞癌(P值分别为0．0275,0．0001和0．0174);而p27在低分化型鳞癌的表达量显著低于分化型鳞癌(P=0．0042)。cyclin D1与cyolin E,cyclin D1与CDK4之间呈显著正相关;而cyclin D1与p27呈显著负相关。4种基因蛋白的表达与淋巴结转移均无相关性。结论 cyclhi E、cyclin D1、CDK4和p27的表达与食管癌的分化密切相关;正负性细胞周期调控蚩白表达的失衡是导致癌变的重要原因之一。     

p27和cyclin E在胆囊癌中表达及与临床病理关系的研究

目的 :探讨p2 7蛋白及细胞周期素E(cyclinE)与胆囊癌发生和发展的关系。方法 :应用免疫组化SABC法检测 5 4例胆囊癌、4 8例胆囊腺瘤及 5 0例胆囊正常黏膜中p2 7及cyclinE表达情况 ,同时结合临床病理资料进行分析。结果 :5 4例胆囊癌中 ,8例 (15 % )p2 7高表达 ,4 4例 (81 4 8% )cyclinE表达 ;4 8例胆囊腺瘤中 ,2 9例 (6 0 % )p2 7高表达 ,2 7例 (5 6 2 5 % )cyclinE表达 ;5 0例胆囊正常黏膜中 ,35例 (70 % )p2 7高表达 ,2 6例 (5 2 % )cyclinE表达。p2 7蛋白在胆囊癌中的表达明显降低 ,三者之间差异有极显著意义 ,P <0 0 0 5。另外 ,p2 7在胆囊癌中表达与癌细胞的分化程度差异有显著意义 ,P <0 0 5 ;低分化癌p2 7表达较低 ,高分化与低分化的p2 7表达差异有显著意义 ,P <0 0 5。p2 7低表达的患者 1年生存率显著降低。cyclinE在胆囊癌中表达与癌细胞的分化程度和肿瘤的病理分期有关。p2 7和cyclinE在胆囊癌中表达存在着相反的联系。结论 :p2 7是细胞周期的负调控因子和潜在的肿瘤抑制因素。p2 7蛋白的降低和cyclinE的过表达在胆囊癌的发生中可能起着重要作用。p2 7是胆囊癌预后的一个可靠指标。     

Expression of p27Kip1 and cyclin D1 proteins is inversely correlated and is associated with poor clinical outcome in human gastric cancer.

BACKGROUND AND OBJECTIVES: p27Kip1 is an inhibitor of cyclin-dependent kinases and is speculated to be a potential prognostic indicator in numerous human cancers. We investigated expression of p27Kip1 along with cyclin D1 in gastric cancer to estimate the clinical utility of p27Kip1. METHODS: Immunohistochemical assay for p27Kip1 and cyclin D1 proteins was performed in 64 patients with primary gastric cancer. Correlation between p27Kip1 expression and clinical-biological parameters including patient survival was analyzed. RESULTS: p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients and cyclin D1 was overexpressed in 22 (34.4%) out of 64. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P = 0.015) and was also reduced in the tumors with high S-phase fraction (86.7%, 26/30) compared with tumors showing low S-phase fraction (41.2%, 14/34; P = 0.0002). Expression of p27Kip1 and cyclin D1 was inversely correlated (P = 0.021). In univariate analysis, extent of the disease (P < 0.001), expression of cyclin D1 (P = 0.0001), and reduced expression of p27Kip1 (P = 0. 0006), were statistically significant to predict patient's outcome, but depth of invasion (P = 0.008) and pathologic stage (P = 0.009) emerged as significant prognostic indicators in multivariate analysis. CONCLUSION: Expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 seems to have potential as a prognostic marker in the management of gastric cancer patients.