p53和nm23联合表达对食管鳞癌淋巴结转移的影响

目的：探讨ｐ５３ 和ｎｍ２３ 表达作为食管鳞癌转移标志物的实用价值。方法：采用免疫组化方法检测８５ 例原发性食管鳞癌中ｐ５３ 和ｎｍ２３ 蛋白表达。结果：６３－５３ ％ （５４／８５） 肿瘤呈ｐ５３ 阳性表达,ｐ５３ 阳性表达与肿瘤淋巴结转移和ＴＮＭ 分期有关（Ｐ值均为０－００１）。４０ ％（３４／８５） 肿瘤为ｎｍ２３ 低表达。ｎｍ２３ 低表达与肿瘤浸润深度、淋巴结转移、ＴＮＭ 分期有关（ Ｐ值分别为０－０３２、０－００１、０－００１） 。单因素分析显示：ｐ５３ 和ｎｍ２３ 表达为影响淋巴结转移的主要因素（ ＯＲ值分别为６－９８４ 和０－０８７,Ｐ＜０－００１）。多因素分析显示：ｎｍ２３ 表达是影响淋巴结转移的一个独立因素（珘ｂ＝ － ０－８４８１ , ＯＲ＝ ０－１８１, Ｐ＝ ０－０００１） 。ｐ５３阳性肿瘤具有高度淋巴结转移的倾向（珘ｂ＝ ０－３１５０, ＯＲ＝２－２８４,Ｐ＝ ０－０５６５）,其它临床病理学参数与淋巴结转移之间未见明显关系（Ｐ＞ ０－０５） 。ｐ５３ 和ｎｍ２３ 异常表达之间呈负相关（ｒｓ＝ － ０－３８４９ ,Ｐ＝ ０－０００３）,在促进肿瘤的进展和转移过程中起联合作用。结论：ｐ５３ 和ｎｍ２３ 联合表达对判断食管鳞癌患者     

Effect of the codon 72 polymorphism (c.215G>C, p.Arg72Pro) in combination with somatic sequence variants in the TP53 gene on survival in patients with advanced ovarian carcinoma

This study was conducted to evaluate the frequency and prognostic impact of TP53 alterations stratified for the TP53 codon 72 polymorphism (c.215G>C, p.Arg72Pro) in a cohort of 109 patients with advanced ovarian carcinomas. TP53 sequence variants were observed in 80 of the 109 (73.4%) tumors and were significantly associated with grade of differentiation (P=0.001). A tendency towards higher frequency of sequence variants in tumors with higher FIGO stages was seen (P=0.05). The type of TP53 sequence variant (transition A:T>G:C vs. G:C>A:T at CpG dinucleotides, and transversion G:C>T:A) had significant correlation with patients' age (P=0.04) with more A:T>G:C in patients over 60 years old. No significant associations were found between frequency of sequence variants and age at diagnosis, histological type, size of residual tumor after primary surgery, or long-term survival. Analyses of the codon 72 polymorphism in tumor DNA gave a higher frequency of homozygosity/hemizygosity than expected from the population frequency, particularly for the Pro allele. Tumors homozygous or hemizygous for the Pro allele had significantly higher frequency of TP53 sequence variants, particularly of the nonmissense type (P=0.002), and patients with these types of alterations had significantly shorter survival (P=0.04). TP53 protein accumulation, determined by immunohistochemistry (IHC), was found in 67.9% (74 out of 109) of the tumors, was significantly more common among serous than nonserous ovarian carcinomas (P=0.008), and had a significant effect on progression-free survival (P=0.03). p63 (TP73L; formerly TP63) and p73 (TP73) protein accumulation detected by IHC was seen in 67.9 and 0% of the tumors, respectively. A significantly higher frequency of p63-positive cases was seen among serous tumors (P=0.008) and tended to increase with increasing FIGO stages (P=0.05), but had no significant effect on survival. No association between p63 protein accumulation and TP53 protein accumulation was seen.     

C-erbB-2, p53, and nm23 gene product expression in breast cancer in young women: Immunohistochemical analysis and clinicopathologic correlation

We studied c-erbB-2, p53, and nm23 gene products in 112 primary breast carcinomas. Fifty patients were aged 35 years or younger, and 62 were aged 36 to 50. Clinicopathological criteria including clinical stage, hormone receptor status, histological types, histological grades, and lymph node status, were reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed. Immunohistochemical findings were assessed semiquantitatively. Correlation between clinicopathological criteria, survival data, and immunohistochemical findings have been made. Patients aged younger than 35 years with stage I to II disease had a shorter DFS (P = .03) than older patients. However, no other clinicopathological finding was associated with age. Neither was there association between age and c-erbB-2, p53, or nm23 patterns of expression. p53 positivity was associated with high histological grade (P = .003) and with progesterone receptor negativity (P = .045). Nm23 nuclear positivity was associated with early clinical stages (P = .011) and with absence of axillary lymph node metastasis (P = .007). p53 and c-erbB-2 overexpression were associated with shorter OS while nm23 nuclear positivity was associated with longer OS in univariate and multivariate analyses. Univariate analyses showed that c-erbB-2 or nm23 were potentially important prognostic factors in women aged 35 years or younger while p53 was associated with prognosis in women aged 36 to 50. Cox model analysis indicated that c-erbB-2 alone was associated with prognosis in women 35 years and younger, whereas p53 alone was associated with prognosis in 36-to 50-year-old women. These results suggest that breast cancer in the youngest women has some biological specificity.     

Expression of p300 and CBP is associated with poor prognosis in small cell lung cancer

Purpose: To investigate the correlation among p300, CBP and MLL expression and the clinicopathological characteristics in resected SCLC patients. Methods: Two hundred and twenty-two resected SCLC patients were included in this study. We evaluated p300, CBP and MLL expression by immunohistochemistry. Results: Patients with high p300 expression had shorter OS and DFS than those with low p300 expression (p = 0.01; p = 0.009, respectively). The patients with CBP-positive tumors had significantly lower OS and DFS than those with CBP-negative tumors (p = 0.005 and p = 0.007, respectively). Moreover, the p300- and CBP-positive (+) group had a significantly poor OS and DFS. The multivariate Cox regression analysis showed that high p300 and CBP expression are independent markers of poor overall survival (p = 0.006; p = 0.017, respectively) in operable SCLC patients. Conclusions: High p300 and CBP expression are independent prognostic markers of poor overall survival for resected SCLC patients. The combination of p300 and CBP expression may be useful in identifying patients with increased risks of cancer recurrence of SCLC.     

p53 but not erbB-2 expression is associated with rapid tumor proliferation in urinary bladder cancer

Tumor proliferation in bladder cancer is associated with tumor behavior. To assess the association between Ki-67 labeling index (LI), p53, and c-erbB-2 overexpression, formalin-fixed tissue samples of 160 patients with transitional cell carcinoma (TCC) of the urinary bladder were studied by immunohistochemistry. Ki-67 LI was strongly associated with tumor stage (P < .0001), tumor grade (P < .0001), and p53 status (P = .0014) but not with erbB-2 overexpression (P > .2). Ki-67 LI was higher in p53-positive tumors (19%) than in p53-negative tumors (14%) when all stages were compared. Ki-67 LI was independent of p53 expression in pTa tumors (p53-positive, 9%; p53-negative, 11%), showing that p53 overexpression alone is not sufficient to induce rapid tumor cell proliferation in pTa tumors. Ki-67 LI also was independent of p53 expression in pT2 to pT4 tumors (p53-positive, 20%; p53-negative, 23%), indicating that p53 expression is not necessary for rapid tumor cell proliferation in advanced stages. However, there was a striking difference in Ki-67 LI between p53-positive pT1 tumors (22.0% ± 8.8 standard deviation [SD]; n = 20) and p53-negative pT1 tumors (9.7 ± 8.3 SD; n = 22; P = .0001). These results suggest that increased proliferation in p53-positive pT1 tumors is caused by additional alterations that occur during tumor progression.     

Apoptosis as an independent prognostic indicator in squamous cell carcinoma of the esophagus

Apoptosis plays a crucial role in determining net cell proliferation and cell turnover in various tumors. The rate of apoptosis in tumor cells has been reported to be a useful prognostic indicator in colorectal carcinoma. We examined apoptosis in 72 specimens of esophageal squamous cell carcinoma, by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) digoxigenin-nick end labeling (TUNEL) method. We examined correlation of apoptosis with outcome, clinicopathological features, and expression of the apoptosis-related proteins p53 and Bcl-2. The percentage of apoptotic cells, or apoptotic index (AI), ranged from 0.8 to 9.4 (mean: 3.47; SD: 2.02). Overall, 5-year survival of patients with high AI (AI > or = 5.0; n = 18) tumors was significantly higher than that of patients with low AI tumors (AI < 5.0; n = 58; 76.9% versus 44.9%; P = 0.042). AI did not correlate significantly with the clinicopathological features of patient age and sex, depth of tumor and histological differentiation, lymph node metastasis, lymphatic invasion, or venous invasion. In p53-negative tumors, the AI was significantly higher than in p53-positive tumors. We concluded that AI may be a useful prognostic indicator in esophageal squamous cell carcinoma following curative surgery, and that apoptosis in this tumor is related to relative underexpression of p53 protein.     

肺癌中P63与P53、E-cadherin、Ki-67表达的比较

目的　比较 p6 3及 p5 3、E cadherin(E cad)、Ki 6 7在肺癌中的表达 ,以了解在不同组织类型肺癌发生发展过程中 ,p6 3与抑癌基因 (p5 3)突变、上皮分化标志基因 (E cad)失活及细胞增殖标志基因 (Ki 6 7)激活有无相关性。方法　采用免疫组化S P法分别检测 6 1例原发性肺癌中 p6 3、p5 3、E cad和Ki 6 7的表达情况。 结果　p6 3在肺鳞癌中阳性率为 10 0 0 % ,而在其他组织类型肺癌中 p6 3基本不表达 ,差异有显著性 (P <0 0 5 ) ;在不同分化程度的肺鳞癌中 p6 3、p5 3的表达差异有显著性 (P<0 0 5 ) ,E cad、Ki 6 7的表达差异无显著性 (P >0 0 5 ) ;E cad的表达在小细胞肺癌与肺鳞癌和肺腺癌之间差异有显著性 (P <0 0 5 ) ;Ki 6 7的表达在各种组织类型肺癌之间差异有显著性 (P <0 0 5 ) ;在不同分化程度鳞癌中 p6 3与E cad的表达呈负相关(P <0 0 5 )。结论　p6 3可作为鳞状上皮源性肿瘤标记物 ,是判断鳞状细胞癌的增殖和分化有意义的指标 ,并可作为鉴别分化差的鳞癌和腺癌、小细胞癌的指标。     

Prognostic and predictive values of Nrf2, Keap1, p16 and E-cadherin expression in ovarian epithelial carcinoma

Objectives: Despite considerable interest in the Nuclear factor-erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap1), p16 and epithelial cadherin (E-cadherin) activation in carcinoma progression, contradictory results regarding association of Nrf2/Keap1/E-cadherin and p16 expression with clinico-pathological features and prognosis have been reported. The predictive value of these markers in ovarian carcinoma is unknown. Methods/Materials: In this retrospective study, 108 cases were evaluated immunohistochemically with antibodies to Nrf2, Keap1, estrogen receptor (ER), p16 and E-cadherin. The results were compared with histological and clinical data, disease-free survival (DFS) and overall survival (OS). Results: A cohort of 108 ovarian carcinomas (47 serous, 23 mucinous, 13 endometrioid and 25 clear cell), including 68 FIGO stage I-II cases and 40 FIGO stage III-IV cases was studied. The age of patients (P=0.005), FIGO stage (P<0.001), immunohistochemical expression of Keap1 (P<0.000), E-cadherin (P=0.045), p53 (P=0.003), p16 (P<0.001) and ER (P=0.004) were significant factors between different histological subtypes. Patients with serous carcinoma were older in age, presented with more advanced stage disease, worst prognosis, highest Keap1 expression and least percentage of E-cadherin immunoreactivity. In univariate analysis, FIGO staging (P=0.000 for DFS; P=0.000 for OS), Nrf2 (P=0.010 for DFS; P=0.001 for OS), and p16 (P=0.004 for DFS; P=0.019 for OS) were associated with worse prognosis. After multivariate analysis, FIGO staging and Nrf2 remained significance prognostic factors. Conclusions: There were differences in the expression of Nrf2, Keap1, p16 and E-cadherin between different ovarian carcinoma subtypes. In multivariate analysis, FIGO stage and Nrf2 expression were associated with poorer DFS and OS.     

The significance of immunohistochemical expression of Ki-67, p53, p21, and p16 in meningiomas tissue arrays

Although histologic grading of meningiomas has prognostic and clinical implications, it is difficult in some cases to predict the outcome of patients. There have been several efforts to evaluate the use of different immunohistochemical markers for predicting meningioma prognosis. We analyzed the immunohistochemical expression of Ki-67, p53, p21, p16, and PTEN proteins in 130 meningiomas (64 benign, 39 atypical, and 27 malignant meningiomas) using tissue microarray. The tumors were graded according to the World Health Organization classification. There was a statistically significant correlation between the expression of Ki-67, p53, p21, p16, and the grade of meningiomas (p0.001). By ordinal logistic regression, p53 and Ki-67 were significantly associated with grade, and an increase of 1% in the labeling index of these markers resulted in an increase in the risk of raising the grade by 2.17 and 1.49, respectively. Histological grade, p53, Ki-67 labeling indices, and overexpression of p16 were strongly associated with decreased event-free survival in univariate analysis. In contrast, multivariate analysis revealed that only tumor grade is an independent factor for predicting meningioma recurrence. We conclude that the Ki-67 and p53 labeling indices are useful additional tools in discriminating atypical from benign or anaplastic meningiomas, especially in histological borderline cases.     

Expression of p63 in reactive hyperplasias and malignant lymphomas

p63 is a recently described p53 homologue. It is involved in survival and differentiation of reserve/stem cells in epithelia. To obtain new insights into the role of p63 in malignant lymphomas (MLs), immunohistochemical staining for p63 and p53 was performed in 126 cases of MLs. p63 was expressed in 38 cases of MLs (30.2%) including 32/61 cases (52.5%) of diffuse large B-cell lymphoma (DLBCL), 1/8 cases (12.5%) of precursor T-lymphoblastic lymphoma (T-LBL), 4/14 cases (28.6%) of follicular lymphoma, 1/6 cases (16.7%) of T/NK cell lymphoma. Among p63 positive cases, p63 was strongly expressed in 15/32 cases of DLBCL and 1/1 case of T-LBL. p63 was not expressed in mantle cell lymphomas, peripheral T-cell lymphomas, marginal zone B-cell lymphomas, plasma cell myelomas and Hodgkin's lymphomas. p63 was coexpressed with p53 in 18/38 p63 positive cases in which only 4 cases were strongly coexpressed. All p63+/p53+ cases were DLBCL. p63 overexpression (above 30%) cases showed significant poor survival (p=0.0228) in DLBCL. However, there was no statistically significant correlation between p63 expression and IPI score on Multivariate analysis. We could speculate that p63 could act indirectly as an oncogene by inhibiting p53 functions. Stage of differentiation of neoplastic lymphocytes appears to have a correlation with p63 expression in MLs.     

Expression of the cell cycle regulatory proteins p34cdc2, p21waf1, and p53 in node negative invasive ductal breast carcinoma.

AIMS: To look for correlations between expression of cell cycle regulatory proteins p34(cdc2), p21(WAF1), and p53 in node negative invasive ductal breast carcinoma, or between these proteins and clinicopathological parameters, and to assess their prognostic value. METHODS: Immunohistochemistry using formalin fixed, paraffin wax embedded sections from 94 breast carcinomas. Adjacent benign epithelial breast tissue was available in 74 cases. Median follow up was 72 months. RESULTS: Nuclear and cytoplasmic p34(cdc2) expression was seen in 80 and 62 tumours, respectively; nuclear expression was seen in adjacent benign epithelium in 12 cases. p21(WAF1) and p53 were positive in 48 and 21 tumours, respectively. High expression of p34(cdc2) in neoplastic nuclei was associated with higher histological grade and p53 expression, but not with tumour size, steroid receptor status, patient age, menopausal status, recurrence, metastasis, disease free survival (DFS), or overall survival (OS). p34(cdc2) in tumour cytoplasm was associated with p34(cdc2) nuclear positivity, high tumour grade, and DFS in univariate but not multivariate analysis. In contrast, p34(cdc2) expression in benign tissue independently predicted DFS and OS in univariate and multivariate analysis. Expression of p53 was associated with high tumour grade and negative steroid receptors, but not with recurrence, metastasis, DFS, or OS. p21(WAF1) expression was not associated with the examined parameters. CONCLUSIONS: p34(cdc2), p21(WAF1), and p53 expression does not predict outcome in node negative breast carcinoma, although p34(cdc2) expression in benign tissue is related to prognosis. The association between p34(cdc2) and p53 implicates p53 in G2-M cell cycle checkpoint control, possibly via mediators unrelated to p21(WAF1).     

Estrogen and progesterone receptors in meningiomas: immunohistochemical (Mib-1, p53) and clinico-morphological correlations

We studied 98 meningiomas including 89 benign, 5 atypical, and 4 anaplastic tumors to determine the immunohistochemical expression of estrogen and progesterone receptors and its prognostic value in comparison to histological grade, Mib-1 and p53. Estrogen and progesterone receptor positivity was observed in 63% and 5% of the cases, respectively. In 79% of meningiomas only a minimal proliferative activity was documented, whereas in 36% we detected an overexpression of the p53 oncoprotein. Anaplastic meningiomas were constantly negative for PgR, ER, and highly positive for Mib-1; 75% were positive for p53. A statistical correlation was demonstrated between p53 protein and Mib-1. Specifically the p53-negative meningiomas were frequently negative for Mib-1 (p = 0.002); conversely the lesions strongly positive for Mib-1 were p53-positive (p = 0.001).     

The prognostic value of USP7 and p53 in advanced hypopharyngeal carcinoma

BackgroundHypopharyngeal squamous cell carcinoma (HPSCC) is a rare malignancy of poor prognosis in head and neck. The aim of the study is to assess the expression and prognostic value of USP7 and p53 in advanced HPSCC.MethodsA retrospective study was performed on a cohort of 103 patients with advanced HPSCC. The immunohistochemical expression of USP7 and p53 was evaluated in all the patients, and the prognostic value of USP7 and p53 was further evaluated. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional recurrence-free survival (LRFS) were assessed using the Kaplan–Meier method and multivariate Cox regression analysis.ResultsIn our study, 78 patients (75.7%) showed low expression of USP7, and the other 25 patients (24.3%) had high expression of USP7; additionally, high USP7 expression was associated with advanced T stage. Low expression of p53 was found in 52 patients (50.5%), while the other 51 patients (49.5%) had a high expression of p53. Our data revealed that low expression of p53 was associated with the advanced N stage (p=0.028). Kaplan–Meier analysis revealed that high expression of USP7 was significantly correlated with the inferior OS, DFS, DMFS, and LRFS, respectively (all p<0.05); additionally, high expression of p53 was correlated with superior OS (p=0.023). The Cox proportional multivariate hazard model revealed that high expression of USP7 was an independent predictor of poor OS, DFS, and LRFS, respectively (all p<0.05).ConclusionsOur findings suggest that USP7 combined with p53 are reliable prognostic factors in patients with advanced HPSCC.     

粘液表皮样癌p16、p53、nm23蛋白及其mRNA表达的临床病理意义

目的：了解粘液表皮样癌中p16、p53、nm23蛋白及其mRNA表达的情况,探讨它们与粘液表皮样癌的病理形态学特征的关系。方法：用HE和组织化学方法对41例粘液表皮样癌诊断,并按WHO标准分为高分化、低分化两组,用免疫组织化学SABC法和原位杂交方法,分别检测41例粘液表皮样癌p16、p53、nm23蛋白及mRNA,用统计学方法分析它们之间的关系。结果：粘液表皮样癌中低分化组,高分化组的p16蛋白失表达率分别是62．5％（15／24）和29．4（5／17）,P＝0．037;p53蛋白的阳性率分别为70．8％（17／24）和23．5％（4／17）,P＝0．003;nm23蛋白的阳性率分别为37．5％（9／24）和64．7（11／17）P＝0．086。p16、p53、nm23mRNA的表达与病理分级无明显相关。结论：p16、p53、nm23mRNA表达与病理分级无明显相关。     

Overexpression of Rsf-1 correlates with pathological type,p53 status and survival in primary breast cancer

Aim: The incidence of breast cancer in developing countries still increasing, to identify novel molecular markers associated with carcinogenesis and prognosis of breast cancer still being implemented. The largest subunit of Remodeling and spacing factor (RSF), Rsf-1, mediates ATPase-dependent chromatin remodeling. Its oncogenic properties have been demonstrated in certain carcinomas. The aim of this study was to examine the prognostic value of Rsf-1 in patients with primary breast carcinoma. Methods: A total of 537 patients with primary breast cancer, and 54 with benign breast hyperplasia, were performed resection surgery in the same period were enrolled. Rsf-1 immunoexpression was retrospectively assessed by immunohistochemistry (IHC). As well as, it relationship with clinicopathological factors and patient survival (LRFS, DFS and OS) was investigated. Results: Compared with benign breast hyperplasia tissues, higher percentage of Rsf-1 positive expression was detected in malignant breast carcinomas. Based on IHC staining extent × intensity scores and ROC analysis, 278 of 526 cancers (52.9%) had high-expression (cut-off values 2.5) of Rsf-1, which correlated significantly to pathologic subtypes of breast cancer (DCIS vs. IDC, P < 0.001; ILC vs. IDC, P = 0.036), bigger tumor size (P = 0.030), higher TNM stage (P = 0.044), and p53-positive expression. In addition, there was a trend that high-expression of Rsf-1 associated with younger age (P = 0.053). We further prove that combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) was correlated with the bigger tumor size (P = 0.018), and higher TNM stage (P = 0.024). Kaplan-Meier survival analysis showed that Rsf-1 high-expression and combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) exhibited a significant correlation with poor overall survival of patients with primary breast cancer, and no association has been identified in relation to LRFS or DFS. Especially, Univariate and multivariate survival analysis demonstrated Rsf-1 expression is an independent prognostic parameter for the overall survival of patients with breast cancer. Conclusions: High-expression of Rsf-1 is associated with pathologic subtypes of breast cancer, aggressive phenotype, p53 positive and poor clinical outcome, which confers tumor aggressiveness through chromatin remodeling, and targeting Rsf-1 gene and the pathway it related may provide new therapeutic avenues for treating breast cancer.     

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.     

Different p53 mutation patterns in colorectal tumors from smokers and nonsmokers

Epidemiological studies consistently find associations between colorectal cancer and cigarette smoking; however, there are little molecular data supporting the association. To examine the relationship between cigarette smoking and colorectal cancer, we compared p53 mutation patterns in colorectal tumors from smokers and nonsmokers. In this study, 153 tumor tissues from colorectal cancer patients, including 63 smokers and 90 nonsmokers, were examined for p53 mutation and p53 protein expression by direct sequencing and immunohistochemistry (IHC), respectively. p53 mutations were detected in 77 of 153 (50.3%) colorectal tumors, and no difference was observed in the p53 mutation frequencies in tumors from smokers and nonsmokers (33 of 63, 50.8% for smokers vs. 44 of 90, 48.9% for nonsmokers, P = 0.743). IHC showed that p53-immunoreactive tumors were positively correlated with p53-mutated tumors (P < 0.0001). G:C-->A:T transition and G:C-->T:A transversion were the predominant types of mutations detected in the tumor p53 genes. G:C-->A:T mutation was relatively more common in nonsmokers than in smokers (93.5% for nonsmokers vs. 77.3% for smokers), although this difference was not significant. The frequency of deletion mutation in smoker tumors, however, was significantly higher than that in nonsmoker tumors (7 of 33, 21.2% for smokers vs. 1 of 44, 2.3% for nonsmokers, P = 0.01). Although there were only a few cases of p53 deletion mutation in this study, the observation of a higher frequency of p53 deletion mutation in smoker tumors supports the association between cigarette smoking and the development of colorectal cancer.