HPC2/ELAC2 polymorphism associated with Japanese sporadic prostate cancer

BACKGROUND: HPC2/ELAC2 gene was identified by linkage analysis from familial prostate cancer (Pca) patients in USA. To determine the association of HPC2/ELAC2 gene with Japanese sporadic Pca, we performed a case-control study focused on two missense polymorphisms. METHODS: We genotyped the two polymorphic sites of Ser217Leu and Ala541Thr in sporadic Japanese Pca patients (n = 285) and matched controls (n = 233). Controls were unrelated Japanese outpatients who had no history of any cancer and normal PSA level (less than 4.0 ng/ml). Statistical analyses were performed by Mann-Whitney's U-test, Fisher's exact test, and logistic regression analysis. RESULTS: We observed a significantly higher frequency of the Thr allele at 541 polymorphic site in Pca patients (8.4%) compared to the control group (2.1%) (P = 0.0030, Odds Ratio (OR) = 4.02, 95% CI = 1.50-10.8). However, this SNP does not correlate with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. No association was identified at Ser217Leu polymorphic site. CONCLUSIONS: Our results indicate that Thr allele at 541 in HPC2/ELAC2 has strong significance in the predisposition of sporadic Pca in Japan. This polymorphism can be useful to predict the personal Pca risk, which lead the effective screening of Pca.     

Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence

INTRODUCTION: CXCR4 is a chemokine receptor that has recently been implicated to play a pivotal role in breast cancer growth and metastasis. In animal models, reduction of CXCR4 expression significantly abrogated metastatic disease and prolonged survival. In human breast cancers, CXCR4 overexpression may portend a worse clinical course. Recent data suggest that HER-2 up-regulates CXCR4, but whether this is applicable in the clinical setting is not known. In this study, we evaluated the role of CXCR4 overexpression in breast cancer and determined whether it can serve as a potential marker of tumor recurrence in HER-2 negative tumors. METHODS: One hundred three patients with stages I to III breast cancers and 6 benign breast tissues were prospectively accrued and analyzed. Study homogeneity was maintained by standardized treatment, surveillance, and compliance protocols. CXCR4 levels were detected using Western blots and results were quantified against 1 microg of HeLa cells (positive controls). HER-2 expression was evaluated using the Hercep program, (Dako Corp., Carpinteria, CA) with a positive result defined as > or = 2. CXCR4 expression was defined as low (<6.6-fold) or high (> or = 6.6-fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included Spearman's correlation, independent samples t-test, Kaplan-Meier survival analysis, and log-rank test. RESULTS: All 103 cancer specimens had CXCR4 overexpression (mean 6.6 +/- 4.7), while none of the 6 benign breast tissues had detectable level of CXCR4. There were 36 HER-2 (+) tumors and 67 HER-2 (-) tumors. There was no statistical significance in mean CXCR4 overexpression between HER-2 (+) [5.6] and HER-2 (-) [6.6] cancers (P = 0.3; independent samples t-test). Recurrences occurred in 18 of 103 patients (17%); 10 occurred in HER-2 (+) tumors, and 8 occurred in HER-2 (-) patients. CXCR4 expression level was not predictive of cancer recurrence (P = 0.80) or overall survival (P = 0.70) in the HER-2 (+) group. However, among HER-2 negative tumors, 7 of 8 recurrences occurred in the high CXCR4 group (P = 0.037). There was no correlation between the degree of CXCR4 overexpression with tumor size (r = 0.13, P = 0.22), nodal status (r = 0.019, P = 0.4), ER/PR status (r = 0.12, P = 0.29), and HER-2 status (r = 0.091, P = 0.36). CONCLUSIONS: CXCR4 overexpression was observed in all 103 breast cancer specimens but was undetectable in benign breast tissues. CXCR4 overexpression does not correlate with tumor size, nodal status, ER/PR status, and HER-2 status. High CXCR4 overexpression had a significant impact on disease-free survival in HER-2 negative breast cancer patients and may help identify a subset of HER-2 negative breast cancers that have a more aggressive biological behavior.     

The association of HER-2/neu amplification with breast cancer recurrence

HYPOTHESIS: Amplification of the HER-2/neu oncogene in 25% of breast cancers is associated with a shortened disease-free survival. DESIGN: Retrospective analysis of a patient population referred to a tertiary care facility for HER-2/neu testing. The mean follow-up was 56 months. SETTING: Large, urban, tertiary care hospital. PATIENTS: From 1995 to 1999, a consecutive sample of 190 patients with breast cancer had tissue samples tested for overexpression of the cell surface oncoprotein by immunostaining (IM) or amplification of the HER-2/neu oncogene by fluorescence in situ hybridization or both. Forty-nine subjects were excluded because they had tissue samples tested at our institution but received their treatment elsewhere. All patients tested for HER-2/neu after diagnosis with breast cancer in 1999 (n = 47) were excluded from analysis because of short follow-up time. One patient was excluded who had in situ ductal carcinoma. The remaining 93 patients were analyzed. RESULTS: Of 93 patients, 40 (43%) had gene amplification. Overall, patients with oncogene amplification had a shorter median disease-free interval (22 months) compared with controls (40 months) (P =.003). Analysis by the Cox regression model showed that the HER-2/neu status remained significantly associated with time to relapse even after adjusting for age and tumor grade (P =.002; adjusted relative risk, 2.4; 95% confidence interval, 1.4-4.4). No association was found between gene amplification and tumor grade (P =.98), estrogen/progesterone receptor status (P = .29 and P = .43, respectively), or lymph node status (P = .98). Seventy-two patients (77%) eventually had disease recurrence, with 18 (25%) of these recurring locally. CONCLUSIONS: The HER-2/neu oncogene is an independent prognostic indicator of a subset of breast cancers that are at high risk of early recurrence, regardless of tumor grade, estrogen/progesterone receptor status, and lymph node status. Patients amplifying the HER-2/neu oncogene have a shorter disease-free survival than patients without the oncogene.     

The Val158Met polymorphism of the catechol-O-methyltransferase gene is associated with the PSA-progression-free survival in prostate cancer patients treated with estramustine phosphate

OBJECTIVE: The aim of our study is to find out the good responders for estramustine phosphate (EMP) therapy in patients with prostate cancer. We have focused on the metabolism of EMP and studied the association between a functional single-nucleotide polymorphism in the catechol-O-methyltransferase gene (Val158Met of COMT) and PSA-progression-free survival in Japanese patients with prostate cancer treated by EMP. METHODS: Seventy-two Japanese patients with previously untreated prostate cancer who were found to be eligible for low-dose EMP therapy were enrolled in the study. Genotyping of the Val158Met polymorphism of COMT was conducted by both the polymerase chain reaction-based restriction fragment length polymorphism method and TaqMan assay. RESULTS: Patients with the Val/Val genotype of COMT had a significantly higher PSA-progression-free rate as compared to those with the Val/Met or Met/Met genotype (p=0.027). The adjusted hazard ratio of biochemical PSA failure for the Val158Met genotype of COMT was 2.164 (95% CI, 1.111 to 5.525). CONCLUSIONS: The Val158Met polymorphism of COMT is associated with the PSA-progression-free rate of EMP-treated patients in prostate cancer.     

The impact of HER-2 status on local recurrence in women with stage I-II breast cancer treated with breast-conserving therapy

This study was undertaken to determine whether overexpression of the oncogene HER-2 is associated with an increase in local recurrence in women with early stage breast cancer treated with breast-conserving therapy (BCT). A retrospective review of the medical records of all women treated with stage I-II invasive breast cancer from 1991 through 2001 was performed. Of 596 eligible patients treated in that time period, immunohistochemical testing for HER-2 expression was performed in 352 patients (59%): 266 patients (76%) were HER-2 negative and 86 patients (24%) were HER-2 positive. Median follow-up was 5.4 years. The patient characteristics for the two groups were compared for age, pathologic T and N stage, number of positive nodes, estrogen receptor (ER) and progesterone receptor (PR) status, radiation treatment, and use of hormonal therapy or chemotherapy. There were no significant differences in any of these parameters between the two groups (all p > or = 0.10). Local recurrence at 5 years was 2% in the HER-2-negative group and 0% in the HER-2-positive group (p = 0.15). There was no difference in local recurrence after BCT between HER-2-positive and negative breast cancers at 5 years. Therefore HER-2 overexpression does not appear to be a contraindication to BCT.     

COMT基因Val158Met多态性在BRCA1/2基因无突变的遗传倾向乳腺癌中的分布

目的探讨Catechol-O-methyhransferase（COMT）基因Val158Met（G→A）多态性在BRCA1／BRCA2基因无突变的具有遗传倾向乳腺癌人群中的分布及其与乳腺癌发病风险的相关性。方法对114例无BRCA1／BRCA2突变的家族性或早发性乳腺癌患者和121例正常对照者进行COMT基因第4外显子的聚合酶链反应扩增,随后进行DNA直接测序鉴定Val158Met多态的基因型,比较基因型分布和发病风险的关系;相对危险比值比（oddratio,OR）及95％可信区间（confidence interval,CI）应用非条件Logistic回归分析计算。结果COMT基因Val158Met多态的GG,GA和AA基因型在病例组中的分布频率分别为0．58（65例）,0．32（36例）和0．10（11例）;在对照组的分布频率分别为0．60（66例）,0．37（41例）和0．03（3例）。在早发性乳腺癌人群中,含A基因型的频率为0．57（21例）,显著高于家族性乳腺癌的0．35（26例）（P=0．026）。以GG基因型为参照,AA基因型（158Met）显著提高了乳腺癌的发病危险（OR=3．15;95％CI：0．70～14．19）（P=0．039）,在绝经前妇女尤为明显（OR=9．98;95％CI：1．00～99．64）（P=0．004）;在体质指数（body mass index,BMI）≤23kg／m^2的妇女中,AA纯合基因型（158Met）临界显著提高了乳腺癌的发病危险（OR=7．57;95％CI：0．57～101．28）（P=0．056）。结论COMT基因Val158Met可能与乳腺癌、特别是绝经前或早发性乳腺癌的遗传易感性有关,可作为低外显率的乳腺癌易感基因位点。     

Concordance of the hormone receptors and correlation of HER-2/neu overexpression of the metachronous cancers of contralateral breasts

The primary objective of this study was to evaluate the relative prevalence of estrogen receptor-negative contralateral breast cancer to the first primary cancer and to assess the correlation between the relative overexpression of HER-2/neu in the first primary cancer and contralateral breast cancer. A total of 144 women diagnosed with cancers in contralateral breasts were identified from the Henry Ford Health System tumor registry. Data were retrieved from electronic databases and medical records. Women were dichotomized into users and nonusers of tamoxifen. Hormone receptors were scored as positive or negative. HER-2/neu overexpression, assessed by immunohistochemistry, was scored as 0, 1(+), 2(+), or 3(+). Concordance between hormone receptors of the two cancers was low (kappa = 0.27, p = 0.06). Stratification of women by tamoxifen therapy yielded an almost fivefold increase in the proportion of estrogen receptor-negative cancers among the users, while the proportion of cancers expressing no estrogen receptor remained the same among the nonusers (39.6% versus 40.6%). Matched, archived, paraffin-embedded specimens of the first and contralateral breast cancers were available for 57 women. The correlation between the relative overexpression of HER-2/neu between the first primary and the contralateral breast cancer was 0.4 (p = 0.002). The higher prevalence of estrogen receptor-negative contralateral breast cancer among tamoxifen users concurs with previous reports. The biological mechanism for this observation is not understood; however, it has been proposed that tamoxifen inhibits the proliferation of estrogen receptor-positive breast cancer cells, while estrogen receptor-negative cells may continue to grow because of selective pressure. The correlation between HER-2/neu overexpression in the matched first primary and contralateral breast cancers was statistically significant, suggesting that the diagnosis of HER-2/neu overexpression in contralateral breast cancer is associated with HER-2/neu overexpression in the first primary cancer.     

Her-2/neu expression in prostate cancer: high level of expression associated with exposure to hormone therapy and androgen independent disease

PURPOSE: HER-2/neu is a proto-oncogene that encodes a transmembrane receptor belonging to the family of epidermal growth factor receptors. Increasing evidences indicates that HER-2/neu may contribute to hormone resistance in prostate cancer. We investigated HER-2/neu expression in primary, androgen dependent and advanced androgen independent prostate cancer, and its potential value as a marker of disease progression. MATERIALS AND METHODS: Immunohistochemical testing was performed to investigate HER-2/neu expression in 81 patients with prostate cancer, including 31 with pathological stage C disease treated with radical prostatectomy without preoperative androgen ablation therapy (untreated group), 30 with pathological stage C disease treated before surgery with androgen ablation therapy (treated group) and 20 with advanced androgen independent prostate cancer (androgen independent group). Tumors were classified based on the percent of tumor cells showing HER-2/neu membrane immunoreactivity as low (50% or less) and high (50% or greater) expression. RESULTS: Of the 31 prostate tumors in the untreated group 9 (29%) showed high HER-2/neu expression versus 15 of 30 (50%) in the treated and 17 of 20 (85%) in the androgen independent groups. The difference in HER-2/neu expression was significant in the untreated and androgen independent (p <0.001) and in the treated and androgen independent (p = 0.016) groups. There was a significant association of Gleason score with HER-2/neu expression in the untreated group (p = 0.038) but not in the treated group. No association was found of tumor substage with HER-2/neu expression. In the untreated group patients with tumors showing high HER-2/neu expression had a decreased survival rate (p = 0.044). CONCLUSIONS: High HER-2/neu expression is highly associated with exposure to hormone therapy and androgen independence. It may contribute to androgen independence in prostate cancer and identify patients with prostate cancer more likely to have disease progression, particularly those not exposed to previous hormone therapy.     

Antibody immunity to prostate cancer associated antigens can be detected in the serum of patients with prostate cancer

PURPOSE: Several immune based therapies targeting prostate cancer associated proteins are currently undergoing clinical investigation. In general, however, little is known about the immunogenicity of prostate cancer or which prostate cancer associated proteins elicit immune responses. We determine whether patients with prostate cancer have antibody immunity to known prostate cancer associated proteins, what the prevalence of this immunity is and whether immunity to individual proteins is associated with the stage of disease. MATERIALS AND METHODS: We evaluated the inherent humoral immune response against prostate specific antigen (PSA), prostatic acid phosphatase, p53 and HER-2/neu, all known prostate cancer associated proteins, in 200 patients with various stages of disease and male controls. RESULTS: Antibody immunity to PSA was significantly different between the patient (11%, 22 of 200) and control populations (1.5%, 3 of 100, p = 0.02), and titers 1:100 or greater were particularly prevalent in the subgroup of patients with androgen independent disease (11%, 6 of 56). Antibody immunity to prostatic acid phosphatase and p53 was detected (5.5%, 11 of 200 and 6%, 12 of 200), and was not different from the control population (4%, 4 of 100, p = 0.57 and 7%, 7 of 100, p = 0.74). Antibody immunity to HER-2/neu was significantly higher in patients with prostate cancer (15.5%, 31 of 200) compared to controls (2%, 2 of 100, p = 0.0004), and titers 1:100 or greater were most prevalent in the subgroup of patients with androgen independent disease (16%, 9 of 56). CONCLUSIONS: These findings suggest that prostate cancer is an immunogenic tumor. Moreover, for PSA and HER-2/neu the prevalence of antibody immunity was higher in patients with androgen independent disease, indicating that even patients with advanced stage prostate cancer can have an immune response to their tumor.     

新型肿瘤标记物P504S对前列腺癌诊断的价值

目的应用新型肿瘤标记物P504S蛋白在前列腺组织中的表达，来辅助前列腺癌诊断。方法回顾性分析我院65例前列腺病理切片，50例确诊为前列腺癌。其中包括35例术前穿刺确诊为前列腺癌，15例前列腺偶发癌；l5例为良性前列腺增生。所有65例标本都进行P504S蛋白表达的免疫组织化学染色。结果P504S在确诊为前列腺癌的标本中阳性率为84％，而良性前列腺增生中未见阳性表达。P504S的表达水平与Gleason评分存在一定相关性。当Gleason评分大于等于7分时，P504S阳性表达水平较高；而Gleason评分小于7分时，P504S阳性表达水平较低。两组间构成比存在显著性差异。结论应用P504S蛋白表达检测有助于辅助前列腺癌的病理诊断，特别适合于体积较小的前列腺穿刺标本进行良恶性鉴别。同时P51MS也有助于前列腺癌的病因研究和探索。关键词P504S前列腺癌良性前列腺增生     

N-acetyltransferase-2 gene polymorphism as a possible biomarker for prostate cancer in Japanese men

BACKGROUND: The purpose of this study was to determine the frequency of a polymorphism of the candidate metabolic enzyme N-acetyltransferase-2 (NAT2) in Japanese prostate cancer patients and Japanese non-cancer controls, in order to determine if an association exists between NAT2 genotype and the occurrence, clinical stage and grade of prostate cancer. METHODS: In the present case-control study, 111 patients with prostate cancer and 152 controls were genotyped for the NAT2 polymorphism using the polymerase chain reaction-based restriction fragment length polymorphism method. The NAT2 genotypes (slow or rapid acetylator genotype) were determined by the combination of three known NAT2 mutant alleles (M1, M2, M3) and the wild-type allele. RESULTS: The NAT2 slow acetylator genotype was statistically higher among prostate cancer patients (17.1%) compared with controls (8.6%) (Odds ration (OR) = 2.21; 95% confidence interval (CI), 1.04-4.69; P = 0.0289). In addition, there was a statistically increased risk of prostate cancer among smokers with the NAT2 slow genotype (OR = 3.78: 95% CI, 1.48-9.66; P = 0.0041). Furthermore, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with locally advanced and metastatic disease (22.7%) compared with controls (8.6%) (OR = 3.14; 95% CI, 1.40-7.06; P = 0.0051). Lastly, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with high-grade tumors (31.4%) compared with controls (8.6%) (OR = 4.90; 95% CI, 1.97-12.20; P = 0.0010). CONCLUSION: These data demonstrate that the NAT2 slow acetylator genotype plays an important role in determining the risk of developing prostate cancer in Japanese men and is also associated with more clinically advanced and pathologically aggressive disease. Furthermore, a possible interaction between the NAT2 slow acetylator genotype and smoking status was suggested.     

三阴性乳腺癌与HER-2过表达乳腺癌患者的临床病理特征及预后比较

目的 探讨三阴性乳腺癌与HER-2过表达乳腺癌患者的l临床病理特征及预后.方法 回顾1997年1月至2007年1月行手术治疗的725例原发性乳腺癌的临床资料,根据免疫组化染色结果确定三阴性和HER-2过表达乳腺癌表型,并对2组的临床病理学资料进行比较和生存分析.结果 三阴性和HER-2过表达乳腺癌分别占12.29%及24.96%;三阴性乳腺癌有恶性肿瘤家族史者占18.4%,明显高于HER-2过表达组的5.5%(P=0.001);组织学分级3级者占54.0%,也高于HER-2过表达组42.0%(P=0.01);三阴性乳腺癌(74.7%)较HER-2过表达乳腺癌(64.6%)更易发生淋巴结转移(P=0.045);在2年内复发、转移及脑转移(分别为25.3%及8.0%)明显高于HER-2过表达乳腺癌(分别为8.8%和2.2%)(P<0.05),其5年无病生存率(55.6%)明显低于HER-2过表达乳腺癌(69.8%)(P=0.041).2组在年龄、月经状态、肿瘤大小、病理分期、手术方式、病理类型、辅助放化疗、肝肺骨转移比例和总生存率之间差异均无统计学意义(P>0.05).结论 与HER-2过表达乳腺癌相比,三阴性乳腺癌更多有恶性肿瘤家族史,肿瘤恶性度更高,更易发生淋巴结和脑转移,无病生存期更短,预后差.     

前列腺癌CD44及nm23-H1基因表达

目的　探讨在前列腺癌中CD44和nm2 3 H1基因表达的意义。　方法　应用免疫组织化学、银染单链长度构相多态性半定量逆转录聚合酶链式反应及免疫印迹杂交法分别检测 32例前列腺癌石蜡标本及 15例新鲜标本中CD44、nm2 3 H1基因的突变、表达情况。　结果　前列腺癌组织中nm2 3 H1蛋白及mRNA高水平表达 ,转移组nm2 3 H1蛋白表达强度高于非转移组。前列腺癌组织中存在nm2 3 H1基因突变 ,突变检出率为 13 3% (2 / 15 )。前列腺癌转移组中 ,CD44s蛋白表达水平下降。CD44smRNA在癌及非癌对照组织中全部表达 ,但 86 7% (13/ 15 )的癌组织中同时表达CD44v。　结论　nm2 3 H1基因的高表达和CD44v/CD44s基因的表达失衡可能在前列腺癌的恶性进展中共同发挥作用。     

An immunohistochemical study of chromogranin A and human epidermal growth factor-2 expression using initial prostate biopsy specimens from patients with bone metastatic prostate cancer

OBJECTIVES: To investigate, using prostate needle-biopsy specimens at diagnosis from patients with bone metastatic prostate cancer, whether the relationship between neuroendocrine (NE) cell differentiation and human epidermal growth factor-2 (HER-2) expression is a prognostic factor for outcome. PATIENTS AND METHODS: The study included 50 patients diagnosed as having bone metastatic prostate cancer between January 1998 and December 2001. We tested for NE cell differentiation by using immunohistochemical (IHC) staining for chromogranin A (CgA), and for HER-2, using a commercial test for IHC staining. RESULTS: Eleven patients (22%) were positive for CgA; there was a significant difference in the time to recurrence (P = 0.025) but no significant differences in cause-specific survival rate or survival rate after recurrence. In all, 21 patients (42%) were positive for HER-2; the cause-specific survival rate, time to recurrence and survival rate after recurrence were all significantly more favourable in the HER-2-negative group (P = 0.008, 0.049 and 0.025, respectively). In the 49 patients for whom both factors could be determined, there was no significant correlation between CgA and HER-2 positivity. CONCLUSIONS: NE cell differentiation of the primary tumour in patients with bone metastatic prostate cancer does not reflect the prognosis, whereas HER-2 overexpression is a prognostic factor for an unfavourable outcome. These results suggest that NE cell differentiation is not induced by HER-2.     

A retrospective study of bone metastases distribution on 420 whole body scans

420 patients with cancer of breast, prostate, lung and colon were investigated through 99mTc Methylene-diphosphonate whole body scintigraphy. The presence of pathologic radiotracer uptake was qualitatively and quantitatively analyzed in order to establish the metastases distribution. Patient selection was realized over 2455 whole body scintigraphies effectuated between 1998 and 2001 in our Nuclear Medicine Service. All selected cases were metastases with known origin primary cancer. RESULTS: Using the Qui-square Test we have compared the frequency of nine well delimited skeleton regions involved like metastatic site in the different cancer types. We have found a significant statistic difference of the range of frequency only between breast and prostate cancers as well as between pulmonary and prostate cancers. The mean number of the metastatic involved skeletal regions was significantly greater in breast and prostate cancers in comparison with lung and colon cancers (p < 0.0001). The higher metastases site frequency was the rachis, than the pelvis, the ribs and the sternum. The skull metastases localization is more frequent in breast cancer in comparison with all other cancers (7.67% versus less than 4% in other cancer types). The pelvis was more involved for the metastatic process in prostate neoplasm. On the other hand, the highest mean anatomic sites number per patient was found in breast cancer (5.7) and prostate cancer (4.8) related to colon (3.3) and lung (3.0) cancers. CONCLUSIONS: Even some particularities were evident, in our study, between the metastases distribution in these four cancer types, the data are not sufficient to sustain the existence of a characteristic pattern related to the primary cancer origin. Metastases localization could be, however, related to the metastazation mechanism.     

新辅助化疗后Ki-67表达变化对乳腺癌预后的影响及其与分子分型的关系

目的:探讨新辅助化疗(NCT)后Ki-67表达改变对乳腺癌预后的影响及与分子分型的关系。方法:回顾2010—2013年收治的121例接受NCT的II A~III C期乳腺癌患者资料,分析NCT后Ki-67表达变化与乳腺癌预后的关系以及其在不同分子分型中的差异。结果:NCT前Ki-67表达与患者肿瘤大小(r=0.181,P=0.047)、组织学分级(r=0.340,P0.001)及HER-2表达(r=0.335,P0.001)呈正相关。全组患者3年无病生存率(DFS)为73.4%,其中NCT后Ki-67减少、增加、不变患者中3年DFS分别为82.6%、61.1%、68.4%,差异有统计学意义(P=0.034);而不同分子亚型3年DSF分别为Luminal A型70.7%、Luminal B型71.4%、HER-2阳性型80.7%、基底样型(78.7%),4组间差异无统计学意义(P=0.857)。族别、治疗前HER-2状态、病理腋窝淋巴结及NCT前后Ki-67表达改变是乳腺癌患者DFS的独立影响因素(均P0.05)。结论:乳腺癌NCT后Ki-67的变化是乳腺癌患者DFS的独立影响因素,但其变化的影响与乳腺癌的分子分型无明显关系。     

Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women

Although several reports are available on the association between CYP1A1 polymorphisms and breast cancer risk in Caucasian women, it has never been reported in Japanese women. Since breast cancer incidence and clinicopathologic features of breast cancers are different between Japanese and Caucasian women, it is conceivable that the risk factors of breast cancer might also differ. In addition, a preliminary study has shown that the frequencies of the variant allele in the CYP1A1 gene are different among ethnic groups. Therefore, in the present study, we investigated the association of CYP1A1 polymorphisms with breast cancer risk in Japanese women. The association of two CYP1A1 polymorphisms, that is, 3' noncoding region (6235(T/C)) and codon 462 (Ile/Val), with breast cancer risk was analyzed by a case-control study (195 cases and 272 controls). Variant allele 6235C carriers at the 3' noncoding region polymorphism showed a significantly ( p < 0.01) reduced breast cancer risk (odds ratio 0.60; 95% CI 0.41–0.88) as compared with noncarriers, and variant allele 462Val carriers at the codon 462 polymorphism also showed a significantly ( p < 0.05) reduced risk (odds ratio 0.66; 95% CI 0.45–0.96) as compared with noncarriers. The relationship between the genetic polymorphisms and clinicopathologic characteristics of breast cancers was also investigated. Variant allele 6235C carriers showed a significantly ( p < 0.02) higher positivity of lymph node metastasis than noncarriers (54% versus 36%), and tumors measuring less than 2 cm were significantly ( p < 0.03) more frequently observed in variant allele 462Val carriers than noncarriers (50% versus 33%). These results suggest that the CYP1A1 polymorphisms would be useful for predicting breast cancer risk as well as some tumor characteristics in Japanese women.     

Retrospective study of 101 cases with incidental prostate cancer stages T1a and T1b

PURPOSE: The purpose of this retrospective study was to clarify the character of incidental prostate cancer, stages T1a and T1b. METHODS: We analysed 101 cases of incidental prostate cancer. Incidental prostate cancer was diagnosed on the basis of normal digital rectal examination findings, a serum prostate-specific antigen (PSA) level of less than 4.0 ng/mL, and no abnormal computed tomography or ultrasonography findings. All patients were treated at Gifu University Hospital or an affiliated hospital during the period January 1992 through December 2001. RESULTS: There were 64 stage T1a cancers and 37 stage T1b cancers. The mean age of patients was 71.3 years (range 51-87 years). The mean serum PSA level was 1.63 ng/mL (range 0.2-4.0 ng/mL). Thirty-five stage T1a patients (56.5%) and thirty-two stage T1b patients (86.5%) underwent some type of treatment. Total prostatectomy was performed in eight stage T1a cases and fifteen stage T1b cases. Pathological diagnoses were as follows: pTx (n = 1), pT0 (n = 5) and pT2 (n = 2) for stage T1a cancers, and pT0 (n = 6), pT2 (n = 8) and pT3 (n = 1) for stage T1b cancers. Only one stage T1b cancer recurred. CONCLUSION: The outcome of patients with incidental prostate cancer was satisfactory; disease recurred in only one case of stage T1b cancer and there were no cases of PSA failure, although the pathological diagnosis in nine of the fifteen stage T1b cases (60.0%) treated with total prostatectomy was pT2 or pT3. Careful monitoring was indicated for stage T1a cancer, and some treatment was necessary for stage T1b cancer.     

High incidence of HER-2 positivity in inflammatory breast cancer

HER-2 is over-expressed in around 25% of human breast cancers, and is associated with poor outcome. We examined the incidence of HER-2 status in inflammatory breast cancer (IBC). Forty-nine newly diagnosed IBCs were studied. Formalin-fixed paraffin-embedded pre-treatment tissue biopsies were examined immunohistochemically for the over-expression of the HER-2 protein and gene using the HercepTest and FISH assay. Clinical outcome was compared between the HER-2 positive (HercepTest score 3 + and FISH positive) and negative groups. Fifty-two per cent of the IBCs examined were HER-2 positive. The HER-2 positive group were demographically comparable to the HER-2 negative group. Ninety-six per cent of the HER-2 positive patients responded to primary chemotherapy compared to 76% of the HER-2 negative (P = 0.09). No significant differences in outcome emerged between the two groups. In conclusion, this study found the incidence of HER-2 protein over-expression in IBC is higher than previously reported in non-IBC. Early HER-2 directed therapy (such as the monoclonal antibody trastuzumab) as a part of multimodal treatment may improve outcome in this poor prognosis cancer.     

Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients

BACKGROUND: Oncogene amplification and chromosomal anomalies are found in many solid tumors and are often associated with aggressiveness of cancer. We evaluated the frequency and the association of c-myc and androgen receptor (AR) gene amplification and gain of chromosome 8 or X in prostate cancer in Japanese patients. METHODS: We examined a total of 42 prostate cancer specimens, using fluorescence in situ hybridization (FISH). Dual-labeling hybridization with a directly labeled centromere probe for chromosome 8 or X together with a probe for the c-myc or AR locus was performed. RESULTS: Gain of chromosome 8 was identified in 54.8% of specimens and was associated with Gleason sum and nuclear anaplasia in untreated prostate cancers. c-myc gene amplification was found in 14.3% of specimens. Gain of chromosome X was identified in 42.9% of specimens. AR gene amplification was detected in 0 of 37 untreated prostate cancers, but in 1 of 5 hormone-refractory prostate cancers. CONCLUSIONS: Our results suggest that c-myc and AR gene amplification and gain of chromosome 8 or X may be associated with the development and progression of prostate cancers. These results obtained in Japanese cases are consistent with the results observed in prostate cancer in Western countries.