TS、p53基因产物表达水平与直肠癌预后的关系

目的：探讨TS基因和p53基因产物表达与直肠癌术后复发转移和预后的关系。方法：采用免疫组织化学方法对42例直肠癌手术标本中的TS基因和p53基因产物进行检测和分析：结果：TS基因产物的高表达率为45．5％(20／42)，p53基因产物的高表达率为43．2％(19／42)。TS基因产物低表达患的局部复发率和远处转移率明显低于高表达患(P=0．014，0．005)，无病生存期明显长于高表达患(P=0．0006)：在24例术后辅助化疗患中，TS基因产物低表达患的局部复发率和远处转移率均明显低于高表达患(P=0．007，0．005)：p53基因产物高表达与局部复发、远处转移以及无病生存期之间未见明显的相关性。多因素分析结果显示TS基因产物表达是影响直肠癌患术后无病生存期的独立因素。结论：TS基因产物表达与直肠癌术后的复发转移和无病生存期有关。     

Thymidylate synthase expression in rectal cancer and proliferation,assessed by cyclin A and Ki-67 expression

BACKGROUND: Levels of the enzyme thymidylate synthase (TS) are of prognostic significance in colorectal cancer. It may be argued that the levels of TS merely reflect the proliferative activity and could be replaced by markers of proliferation. MATERIALS AND METHODS: We used immunohistochemical approaches to examine the expression of TS, Cyclin A and Ki-67 in morphologically well-defined tumor areas in consecutive slices of rectal cancer, using the antibodies TS 106, NCL-Cyclin A and Mib-1. RESULTS: There was a linear relationship between Cyclin A- and Ki-67-positive cells (p < 0.0001). There did not seem to be any significant relationship between TS-expression and the frequency of Cyclin A-positive cells (p = 0.1) but a significant correlation was observed between TS-expression and the frequency of Ki-67-positive cells (p = 0.02). CONCLUSION: TS, immunohistochemically-detected in rectal cancer cells, is not associated with an accurate assessment of the proliferative stage. The prognostic value of TS determination can only partly be explained by the proliferative activity.     

Ki-67、p53及HER-2在结直肠癌组织中表达的临床意义

目的:了解Ki-67、p53及HER-2在结直癌组织中表达的临床意义.方法:采用免疫组化法,观察Ki-67、p53、HER-2在39例结直肠癌组织中的表达特点,并与Dukes分期、组织分化等临床病理特征进行研究探讨.结果:Ki-67、p53及HER-2在结直肠癌组织中的阳性表达率分别为82.1％、56.4％及10.3％;在结直肠癌中,Ki-67在年龄大小和有无淋巴结转移表达中有显著差异(P＜0.05);p53和HER-2在患者性别、年龄、部位、分化程度、Dukes分期、淋巴结转移表达无明显差异(P＞0.05);结直肠腺癌组织中Ki-67与p53的表达呈正相关.结论:联合检测Ki-67和p53在结直肠腺癌中的表达有利于对结直肠腺癌恶性程度及患者预后进评估;而HER-2基因在结直肠肿瘤的表达及相关性治疗,仍需要进一步研究、探讨及验证.     

乳腺癌bcl-2、Ki-67、p53表达及意义

目的：探讨bcl-2、Ki-67、p53蛋白在乳腺癌中的表达及其关系。方法：应用免疫组化SP方法，观察56例乳腺癌中的bcl-2、Ki-67、p53的表达情况。结果：bcl-2、Ki-67和p53在乳腺癌中表达率分别为63％，68％，52％，与乳腺癌分级及淋巴结转移密切相关（P＜0．05）。结论：bcl-2、Ki-67、p53的异常表达在乳腺肿瘤发生发展中起重要作用。     

Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion

: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar.

: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis.

: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p = 0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p = 0.04), and these patients had a higher rate of nonbrain distant metastases (p = 0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p = 0.01). There was a positive correlation in the expression of Ki-67 (p = 0.02)(r² = 0.1608), as well as p53 (p < 0.001) (r² = 0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive.

: Differences in biomarker expression between the case and control groups did not serve as significant predictors of brain metastasis or patient survival. There was a strong correlation between lung primary biomarker expression and brain metastasis expression for Ki-67 and p53. Univariate analysis showed that low p53 and high Ki-67 expression predicted poor prognosis. This study shows that there may be a strong correlation between biomarker expression in non-small-cell lung cancer primary tumors and their brain metastases.     

结直肠锯齿状腺瘤、传统腺瘤及结直肠癌中端粒酶、p53及Ki-67的表达比较

背景与目的：结直肠锯齿状腺瘤(serrated adenoma,SA)是2000年被WHO正式命名为独立的一种疾病,与传统腺瘤(traditional adenoma,TA)和结直肠癌(colorectal carcinoma,CRC)比较有其独特的性质。本研究通过对锯齿状腺瘤、传统腺瘤和结直肠癌组织中端粒酶、p53及Ki-67的免疫组化表达比较,探讨锯齿状腺瘤与普通腺瘤的恶性潜能异同及与大肠腺癌的关系。方法：运用免疫组化MaxVision法对37例锯齿状腺瘤、36例传统腺瘤,34例结直肠癌组织标本进行端粒酶、p53及Ki-67检测。结果：端粒酶在锯齿状腺瘤、传统腺瘤和结直肠癌组间差异有统计学意义(P<0.05),结直肠癌组阳性率高于锯齿状腺瘤组(P<0.05),锯齿状腺瘤组高于传统腺瘤组(P<0.01);Ki-67在锯齿状腺瘤与传统腺瘤两组差异无统计学意义(P>0.05),结直肠癌组的阳性率则明显高于锯齿状腺瘤和传统腺瘤组(P<0.01);结直肠癌组p53阳性率高于传统腺瘤组(P<0.01),传统腺瘤组高于锯齿状腺瘤组(P<0.01)。结论：端粒酶、p53及Ki-67检测显示：锯齿状腺瘤是一种具有较强活性的腺瘤,端粒酶的激活可能在其癌变过程中起一定作用。     

Predictive value of cell cycle markers p53, MDM2, p21, and Ki-67 in superficial bladder tumor recurrence.

The aim of the study was to determine whether the expression of the cell cycle markers p53, MDM2, p21, and Ki-67 was predictive of superficial bladder cancer recurrence and to compare the relative predictive power for tumor recurrence of a cell cycle index based on the number of abnormally expressed cell cycle markers with a clinicopathological index based on primary clinical tumor characteristics. The expression of p53, MDM2, and p21 proteins and the value of the Ki-67 index were analyzed for 244 patients. One hundred ninety-four lesions were determined to be superficial papillary tumors (pTa), whereas 50 tumors invaded the lamina propria (pT1). Tumor grade was noted low (grade 1) in 83 cases and high (grades 2-3) in 161 cases. An avidin-biotin peroxidase method was performed using monoclonal antibodies against p53, MDM2, p21, and Ki-67 antigens after antigen retrieval treatment of formalin-fixed specimens. The cell cycle marker index was created using the number of abnormally expressed cell cycle markers according to the following cutoff points: p53 (>5%), MDM2 (>20%), p21 (<5%), and Ki-67 (>10%). The clinicopathological index was created using the following adverse tumor characteristics: grades G2-G3, stage pT1, multifocality, and diameter of tumors > 3 cm. Cox regression models were used to calculate the relative risks and their 95% confidence intervals associated with disease recurrence for the clinicopathological index and the cell cycle marker index. The chi2 test was performed to describe the correlation between the Ki-67 index and p53, MDM2, and p21 protein expression. Kaplan-Meier survival curves were generated to demonstrate the disease-free survival according to these two prognostic indexes. The clinicopathological index was a strong, independent predictor of disease recurrence where tumors with three or four adverse tumor characteristics at initial resection had over four times the risk of recurrence than tumors with no risk factors (P for trend = 0.0001). A strong correlation was observed between the Ki-67 index >10% and both MDM2 and p21 proteins. MDM2 was overexpressed in 106 tumors (43%), and p53 was overexpressed in 47 (19%); Ki-67 was >10% in 171 cases (70%). Thirty-nine tumors (16%) were p21 negative. The risk of recurrence increased slightly with the number of abnormally expressed cell cycle markers, but when the clinicopathological index was taken into account in multivariate analysis, the cell cycle marker index was not predictive of disease recurrence (P for trend = 0.72). The cell cycle markers studied provided no added prognostic information on disease recurrence after initial resection of papillary superficial tumors when the clinicopathological parameters were taken into account.     

Thymidylate synthase polymorphisms and colon cancer: associations with tumor stage, tumor characteristics and survival

Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. We investigated the role of functional polymorphisms in the TS 5'-UTR promoter enhancer region (TSER, 3 or 2 repeats of a 28-bp sequence) and the 3'-UTR (1494delTTAAAG) and their association with colon tumor characteristics, including tumor stage and acquired mutations in p53, Ki-ras and microsatellite instability. Data from a population-based incident case-control colon cancer study in northern California, Utah and Minnesota (1,206 cases, 1,962 controls) was analyzed using unordered polytomous logistic regression models. In both men and women, individuals with variant TS alleles were at reduced risk of having an advanced stage tumor (metastatic disease: OR = 0.35, 95% CI: 0.2-0.6 vs. wildtype TSER and 3'-UTR). Stage-adjusted survival did not differ by genotype. Men with 1 or 2 variant alleles in both the TSER and 3'-UTR genotypes had a 50% reduced risk of a p53-positive tumor (OR = 0.5, 95% CI: 0.3-0.9 vs. homozygous wildtype TSER and 3'-UTR). Women with 1 or 2 variant alleles for either the TSER or 3'-UTR polymorphism had reduced risk of having any colon tumor that did not vary by mutation status. This study provides some support for associations between TS genotype and colon cancer tumor characteristics.     

Ki-67, Bcl-2 and p53 expression in primary and metastatic melanoma

The aim of this study was to clarify the roles of the tumour proliferation marker Ki-67, the anti-apoptotic protein Bcl-2 and the cell cycle regulator p53 in primary cutaneous and metastatic melanoma. One hundred and seventeen primary melanomas and 18 metastatic tissue samples were analysed for immunohistochemical expression of Ki-67, Bcl-2 and p53. The staining results were correlated with disease progression and clinical outcome. The patient population comprised patients diagnosed with melanoma between 1988 and 1991. The clinical follow-up period for disease recurrence was 4.6 years (median; range, 0.2-7.5 years) and the follow-up period for overall survival was 10.0 years (median; range, 8.6-15.6 years). Ki-67 expression was not a prognostic factor in primary melanoma. High Bcl-2 expression was associated with such adverse prognostic factors as male gender, old age of the patient and tumour ulceration. High Bcl-2 expression was also associated with an adverse prognosis in intermediate-thickness (1.01-4.0 mm) melanomas (n=52) for disease-free (P=0.09) and overall (P=0.08) survival. In multivariate analysis, tumour thickness was the strongest prognostic factor for disease-free survival (P<0.01). High p53 expression indicated a poorer prognosis (P=0.05). In metastatic melanoma, the expression levels of Bcl-2 and p53 were lower than those in their primary counterparts (P=0.08 for each). Ki-67 expression showed no remarkable changes. It can be concluded that high p53 expression in tumour cells is associated with a poorer prognosis in primary melanoma, and high Bcl-2 expression in tumour cells is an adverse prognostic marker in intermediate-thickness primary melanoma.     

p53 and bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time.

B-cell high-grade lymphomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. As bcl-2 and p53 gene deregulations are frequently involved in several types of lymphoid malignancies, we aimed our investigation at the study of the relation between bcl-2 and p53 expression and survival probability in a group of 119 patients with B-cell high-grade lymphoma. These were obtained from the Virgen de la Salud Hospital, Toledo, Spain (73 cases), John Radcliffe Hospital, Oxford, UK (31 cases), and the Istituto Nazionale dei Tumori, Milan, Italy (15 cases). The relation between bcl-2 protein expression and survival was small, depending on the primary localisation of the tumour (in lymph node of mucosae), and lacked a significant correlation with overall survival. In contrast with this, p53 expression was related to survival probability in our series, this relation being both significant and independent of histological diagnosis. p53-positive patients showed a sudden decrease in life expectancy in the first months after diagnosis. Multivariant regression analysis confirmed that the only parameters significantly related with survival were extranodal origin, which is associated with a better prognosis, and p53 expression, which indicates a poor prognosis. Simultaneous expression of bcl-2 and p53 was associated with a poorer prognosis than p53 alone. This is particularly significant for large B-cell lymphomas presenting in lymph nodes. The cumulative poor effect of both p53 and bcl-2 in large B-cell lymphomas, which is more significant in nodal tumours, could confirm the existence of a multistep genetic deregulation in non-Hodgkin''s lymphoma. This indicates that the genetic mechanisms controlling apoptosis and their disregulation are critical steps in the progression of lymphomas.     

Correlation of expression of Ki-67, EGFR, c-erbB-2, MMP-9, p53, bcl-2, CD34 and cell cycle analysis with survival in head and neck squamous cell cancer

The purpose of this study was to clarify the prognostic significance of flow cytometric analysis of DNA, mitotic, apoptotic indices, Ki-67, EGF-R, c-erb-B2, matrix metalloproteinasis-9 (MMP 9), p53, bcl-2, CD 34 in Head and Neck Carcinomas (HNSCC). The analysis was carried out with a set of 217 patients suffering from HNSCC. The parameters of tumors were related to the overall survival (OS) and the event-free survival (EFS). Clinical stage, ploidy and T-N categories influence both survival measures equally and significantly. Grade score did not significantly contribute to the prediction of EFS and OS when entered to the analysis as single factor. Measure of realized proliferation significantly contributed to the risk prediction both in EFS and OS. Cytokinetic parameters generally strongly correlated with grade score and grade correlates, responsible for the increasing risk in combination with other risk factors like clinical stage and/or ploidy. Positivity in bcl-2 and MMP-9 was significantly related to OS of patients (not to EFS). Positivity of EGFR, c-erbB-2, CD34, p53 did not reached statistically significant value in association to EFS or OS.     

Combined role of tumor angiogenesis, bcl-2, and p53 expression in the prognosis of patients with colorectal carcinoma.

BACKGROUND: The objective of this study was to evaluate intratumoral neoangiogenesis in Dukes Stage B and Stage C (AJCC/UICC Stage I and III) colorectal adenocarcinoma and its correlation with nuclear p53 oncoprotein accumulation and cytoplasmic bcl-2 expression as well as to assess the prognostic significance of these features in patient outcome. METHODS: Paraffin embedded specimens from 55 patients with Dukes Stage B (AJCC/UICC Stage I) and 51 patients with Dukes Stage C (AJCC/UICC Stage III) colorectal adenocarcinoma who were treated with surgery were assessed. Patients with lymph node involvement (Dukes Stage C [AJCC/UICC Stage III]) also were treated with postoperative pelvic radiotherapy and adjuvant chemotherapy with 5-fluorouracil and leucovorin with or without interferon-alpha. Immunohistochemistry was performed using the anti-CD31 monoclonal antibody (MoAb) for vessel staining, the DO7 MoAb for nuclear p53 expression, and the clone 124 for cytoplasmic/perinuclear bcl-2 expression. Patient follow-up ranged from 4-70 months (median, 28 months). RESULTS: High vascular grade (microvessel score [MS] >/= 40) was observed in 39 of 106 specimens (37%), a medium MS (16-39) was observed in 29 of 106 cases (27%), and a low MS (7-15) was observed in 38 of 106 cases (36%). Positive expression of the bcl-2 protein in > 10% of cells was observed in 33 of 106 cases (31%), whereas p53 nuclear oncoprotein accumulation in > 10% of cells occurred more frequently (44 of 106 cases [42%]). No correlation among p53 expression, bcl-2 expression, and vascular grade was observed. Stroma infiltration by CD31 positive lymphocytes was associated strongly with increased vessel density (P = 0.0001). In univariate analysis Dukes stage was the only significant prognostic parameter (P = 0.02), whereas p53 and vascular grade showed marginal prognostic significance (P = 0.07 and P = 0.09, respectively). In Dukes Stage C (AJCC/UICC Stage III) patients, high vascular grade was the only parameter that predicted a worse overall survival (P = 0.04). Double stratification showed that patients with high vascular grade and positive p53 expression had a poorer survival (P = 0.03). CONCLUSIONS: The results of the current study suggest that p53 mutations, loss of bcl-2 expression, and tumor angiogenesis are events linked to the processes of metastases and local invasion in patients with colorectal carcinoma. Increased vascularization appears to be the most important prognostic factor in patients with Dukes Stage C (AJCC/UICC Stage III) colorectal adenocarcinoma.     

非霍奇金淋巴瘤组织中突变型p53、bcl-2、Ki-67及survivin蛋白表达及临床意义

目的:探讨突变型p53、bcl-2、Ki-67、survivin在非霍奇金淋巴瘤(NHL)组织中的表达及其临床价值.方法:采用组织芯片技术及免疫组化SP法检测142例NHL和18例良性淋巴结病变组织中突变型p53、bcl-2、Ki-67、survivin蛋白的表达.结果:突变型p53、bcl-2、Ki-67、survivin蛋白在NHL中的表达阳性率分别为55.63%(79/142)、51.41%(73/142)、48.59%(69/142)和60.56%(86/142);与对照组相比具有非常显著性差异(P<0.01).在不同性别以及在不同细胞类别NHL中,突变型p53、bcl-2、Ki-67、survivin蛋白表达阳性率基本一致,统计分析无显著性差异(P>0.05);但在低年龄组、临床Ⅲ-Ⅳ期和高度恶性组突变型p53、bcl-2、Ki-67、survivin蛋白表达阳性率明显高于高年龄组、临床Ⅰ-Ⅱ期和低度恶性组,有显著性差异(P<0.05);突变型p53蛋白与Ki-67蛋白呈正相关(r=0.8769),survivin蛋白与bcl-2蛋白表达呈正相关(r=0.8846).结论:突变型p53、bcl-2、Ki-67、survivin蛋白在NHL组织中高表达,与NHL的发生与发展、细胞恶性程度和组织病理学等级密切相关.     

p53、p27、bcl-2在非小细胞肺癌中表达的研究

目的　研究p53、p2 7、bcl 2三种基因蛋白与非小细胞肺癌 (NSCLC)临床病理特征的关系。方法　应用S P免疫组化法检测 76例手术切除NSCLC标本中三种基因蛋白的表达。结果　 76例标本中 2 8例(36 .84% )p53过度表达 ,34例 (44.74% )p2 7过度表达 ,37例bcl 2过度表达 (48.68% ) ,7例患者p53、p2 7、bcl 2均过度表达。p53阳性表达率随分化程度降低而升高 ,bcl 2和p2 7阳性表达率随分化程度降低而降低 ,且高、低分化组间均有显著性差异 (P <0 .0 5)。但是三种蛋白阳性表达率均与肺癌组织学类型、淋巴结转移及病理分期无明显关系 (P >0 .0 5)。结论　p53、p2 7和bcl 2基因过度表达可能与NSCLC的发生、发展有关     

Isoform expression of CD44 adhesion molecules, Bcl-2, p53 and Ki-67 proteins in lung cancer.

CD44, belongs to the cell adhesion molecule family and is expressed on cell surfaces in several isoforms which are generated by alternative splicing of messenger RNA. These splice variants have been shown in several cancer cell types and are thought to be involved in tumor progression. The aim of the current study was to evaluate the expression of selected CD44 variants on lung cancer cells of various histology and to compare these with other markers of tumor spread. Surgical samples of primary lung carcinoma of various histology were subjected to alkaline phosphatase-anti-alkaline phosphatase complex immunohistochemistry using a panel of monoclonal antibodies: anti-CD44 v5, v6, v7/8, v10, anti-Ki-67, anti-Bcl-2 and anti-p53. Positive cells were scored in a semiquantitative way. The patients were subdivided into groups with and without metastases, as found during surgery. All CD44 variants tested could be demonstrated on lung cancer cells, but the incidence of particular isoforms varied, depending on lung cancer histology. In general, CD44 expression was highest in squamous cell tumors and lowest in anaplastic small cell carcinomas. Squamous cell cancers had high expression of v5 and v6 variants, while in anaplastic large cell and small cell carcinomas v10 was abundant. When Ki-67, Bcl-2 and p53 protein expression was compared to the incidence of CD44 variants, coincidence was found for v10 only. Most of the cases positive for v10 were also Ki-67 positive (p = 0.0146). In 12 cases with metastases, tumor cells had high v6 and Ki-67 expression, but these data were not significant compared to cases without metastases. Overall, these data suggest that v5 and v6 variants are of significance in squamous cell lung carcinoma, presumably in the promotion of metastasis, while in anaplastic small cell or large cell cancers only v10 expression seems to correlate with proteins associated with tumor growth and progression.     

大肠癌组织中HSP27和bcl-2及p53蛋白的表达及其临床意义

目的:探讨热休克蛋白27(heatshockprotein,HSP27)、bcl-2和p53蛋白在大肠癌组织中的表达及其临床意义。方法:运用免疫组织化学SP方法检测HSP27、bcl-2和p53在72例大肠癌组织中的表达,并运用多因素COX比例风险模型分析患者的预后。结果:HSP27在大肠癌组织中的阳性率为69·44%(50/72),bcl-2为54·17%(39/72),p53为59·72%(43/72)。HSP27在高分化腺癌组的表达率为84·85%,显著高于低分化组的28·57%,χ2=29·614,P=0·000。bcl-2和p53在高分化腺癌组的表达率也高于低分化腺癌组,χ2=5·771,P=0·016;χ2=4·714,P=0·030。HSP27和bcl-2在大肠癌中的表达具有相关性,r=0·380,P=0·001。COX回归分析提示,HSP27表达与生存期呈负相关。结论:HSP27和bcl-2及p53与大肠癌耐药有关;联合检测对临床制定合理的化疗方案具有指导意义;HSP27可作为判断大肠癌预后的一个独立预测指标。     

Prognostic significance of Ki-67 nuclear proliferative antigen, bcl-2 protein, and p53 expression in follicular and diffuse large B-cell lymphoma

We analyzed 104 patients with non-Hodgkin’s lymphoma, follicular or diffuse large-B-cell-type lymphoma, in order to evaluate the correlation between clinical characteristics and immunohistochemical parameters. Immunostaining was performed by means of monoclonal antibodies against Ki-67, bcl-2, and p53 expression. Forty-nine of the patients showed follicular lymphoma. A high expression of bcl-2 was found in 93%, high expression of p53 in 57%, and low expression of Ki-67 in 96%. Follicular lymphoma grade III showed a p53 expression (p=0.07) slightly higher than follicular lymphoma grades I and II, not reaching statistical significance. Follicular lymphoma grades I and II tended to express lower Ki-67 and higher levels of bcl-2 expression than grade III (p=0.06). Fifty-five cases showed diffuse large-B-cell lymphoma. Among them, bcl-2 was absent in 39%, whereas p53 and Ki-67 expression were high in 38%. In the diffuse large-B-cell lymphomas, a high bcl-2 expression correlated with stages III and IV (p=0.03) and involvement of more than one extranodal area (p=0.03). High Ki-67 expression was also associated to extranodal involvement of more than one area (p=0.03). Overall survival of patients did not show statistically significant differences regarding Ki-67, bcl-2, and p53 tumoral expression. Prognostic factors for overall survival in the multivariate analysis were age (p=0.02) and LDH (p=0.003). Time to progression was worse among follicular lymphoma with high p53 expression than with mild/moderate p53 expression (p=0.009).     

Thymidylate synthase expression: an independent prognostic factor for local recurrence, distant metastasis, disease-free and overall survival in rectal cancer.

Several studies have suggested that the intratumoral level of thymidylate synthase (TS) in colorectal tumors correlates with survival. We have studied the correlation between TS expression in primary rectal cancer and locoregional recurrence, distant metastases, and survival. TS enzyme levels were evaluated immunohistochemically using the specific monoclonal antibody TS 106 in paraffin-embedded tumors from 243 patients who had undergone primary surgery for rectal cancer during the years 1980-1993. All patients were included in prospective randomized trials aimed at determining the clinical value of a short preoperative course of local radiation therapy (five doses of 5 Gy each). With a median follow-up of 94 months (range, 43-202 months), it was observed by multivariate analysis that Dukes' stage and TS expression were independent prognostic markers of locoregional recurrence (P < 0.001 and P = 0.038, respectively) distant metastasis (P < 0.001 and P = 0.011, respectively) disease-free survival (P < 0.001 and 0.014, respectively), and overall survival (P < 0.001 and 0.020, respectively). By multivariate analysis, preoperative irradiation therapy showed a borderline improvement in locoregional recurrence (P = 0.051). No other factors, such as age, sex, differentiation of the tumor, or p53 expression, were noted to be independent prognostic factors for clinical outcome in these patients. We concluded that the intratumoral expression of TS in primary rectal cancer is an independent prognostic factor for locoregional recurrence, distant metastases, disease-free survival, and overall survival. Patients with low intratumoral TS expression had a significantly better outcome than those with high TS expression.     

Thymidylate synthase polymorphism and survival of colorectal cancer patients treated with 5-fluorouracil

British Journal of Cancer (2002) 86, 1365. DOI: 10.1038/sj/bjc/6600229 www.bjcancer.com© 2002 Cancer Research UK