Biomedical subjects

Shinzaburo Noguchi

Publications and source records attributed to Shinzaburo Noguchi.

At least 37 records · Page 2Linked to original sources

PubMed2005

High thioredoxin expression is associated with resistance to docetaxel in primary breast cancer.

PURPOSE: Thioredoxin overexpression is suggested to be associated with resistance to several chemotherapeutic agents in vitro. In the present study, it has been studied whether or not high thioredoxin expression is associated with resistance to docetaxel therapy in breast cancer patients. PATIENTS AND METHODS: Sixty-three primary breast cancer patients were treated with docetaxel (60 mg/m(2), q3w) for four cycles in the neoadjuvant setting. Expression of thioredoxin, estrogen receptor (ER), p53, BRCA-1, and Bcl-2 in tumor tissues obtained before docetaxel therapy was studied by immunohistochemistry (thioredoxin, p53, BRCA-1, and Bcl-2) and enzyme immunoassay (ER), and relationship of expression of these biomarkers with a pathologic response was investigated. RESULTS: There was no significant correlation between the expression of p53, BRCA-1, or Bcl-2 and a response to docetaxel. However, tumors with high thioredoxin expression showed a significantly lower response rate (0%) than those with low thioredoxin expression (30.6%; P = 0.018) and ER-negative tumors showed a significantly higher response rate (32.4%) than ER-positive tumors (10.7%; P = 0.043). Thioredoxin expression significantly increased after docetaxel therapy (mean, 56.1%) as compared with that before docetaxel therapy (mean, 28.6%; P < 0.0001) but there was no significant association between the extent of increase in thioredoxin expression and response. CONCLUSION: High thioredoxin expression in prechemotherapy tumor samples, but not the increase in thioredoxin expression induced by docetaxel, is associated with resistance to docetaxel in breast cancer. Thioredoxin and ER might be clinically useful in the prediction of a response to docetaxel.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Differentiation of follicular thyroid adenoma from carcinoma by means of gene expression profiling with adapter-tagged competitive polymerase chain reaction.

OBJECTIVE: Since preoperative differentiation between follicular thyroid adenoma (FTA) and carcinoma (FTC) remains very difficult, the purpose of this study was to identify the genes differentially expressed in FTA and FTC in order to construct a diagnostic system based on such genes for differentiation of FTA and FTC. METHODS: Gene expression profiles of 45 FTAs and 22 FTCs were analyzed by means of adapter-tagged competitive polymerase chain reaction (ATAC-PCR) with 2,516 genes (learning set). The genes differentially expressed in FTAs and FTCs were then used to construct a diagnostic system based on the weighted-voting algorithm. In addition, a validation study of this diagnostic system was conducted using 12 FTAs and 6 FTCs (validation set). RESULTS: The diagnostic system for differentiation of FTA and FTC, constructed with the aid of the learning set samples, was based on 60 genes differentially expressed in FTA and FTC, which included several genes previously identified as overexpressed in FTC (DPP4, KRT19 and IGFBP3) or FTA (trefoil factor 3 and thyroid peroxidase). The leave-one-out cross-validation study showed that the accuracy of this diagnostic system was as high as 90% (sensitivity: 77.3% and specificity: 95.6%), and was confirmed by the validation study (diagnostic accuracy: 83.3%; 95% confidence interval: 62.8-95.4%, sensitivity: 66.7% and specificity: 91.2%). CONCLUSIONS: This diagnostic system using the ATAC-PCR assay is expected to be clinically useful for preoperative differentiation between FTA and FTC since ATAC-PCR can be used for the small amount of RNA obtained from fine needle aspiration biopsy.

Adenoma↗

PubMed2005

Postoperative adjuvant therapy with tamoxifen, tegafur plus uracil, or both in women with node-negative breast cancer: a pooled analysis of six randomized controlled trials.

PURPOSE: This article reports the results of a pooled analysis of six randomized trials conducted to study the efficacy of uracil and tegafur (UFT) in the adjuvant treatment of node-negative breast cancer patients. PATIENTS AND METHODS: Six randomized controlled trials on node-negative breast cancer patients were conducted from 1992 through 1995 in Japan that included the three, three-arm trials (control [no adjuvant], UFT, and tamoxifen [TAM] groups) and the three, four-arm trials (control, UFT, TAM, and UFT plus TAM groups). Pooled analysis was performed on the data obtained from these six trials (involving 2,934 patients). RESULTS: Overall survival was compared between the UFT group (including both the UFT group and the TAM plus UFT group) and the non-UFT group (control group and TAM group). A significant difference (P = .04) was observed in 5-year survival rates between the UFT (95.9%) and the non-UFT (94.0%) groups. Overall survival was also compared between the TAM group (TAM group and TAM plus UFT group) and the non-TAM group (control group plus UFT group). The 5-year survival rate (95.2%) in the TAM group was not significantly different from that (93.9%) in the non-TAM group, but the subset analysis showed a significant (P = .01) improvement in the estrogen receptor-positive subset. CONCLUSION: Adjuvant UFT improves the overall survival of node-negative breast cancer patients. Given that UFT has milder adverse effects, it is suggested that UFT can be a useful alternative to doxorubicin and cyclophosphamide, or cyclophosphamide, methotrexate, and fluorouracil in the adjuvant treatment for node-negative breast cancer.

Aged↗

PubMed2005

Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers.

PURPOSE: LATS1 and LATS2 are tumor suppressor genes implicated in the regulation of cell cycle. Methylation status of the promoter regions of these genes as well as its correlation with their mRNA levels were studied in human breast cancers. Correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics of breast tumors were also studied. EXPERIMENTAL DESIGN: Methylation status of promoter regions of LATS1 and LATS2 was studied by a methylation-specific PCR and mRNA expression levels of LATS1 and LATS2 were determined by a real-time PCR assay in 30 breast cancers. In addition, correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics was studied in 117 breast cancers. RESULTS: Methylation-specific PCR showed that of 30 tumors, LATS1 promoter region was hypermethylated in 17 tumors (56.7%) and LATS2 promoter region was hypermethylated in 15 (50.0%) tumors. LATS1 mRNA levels in breast tumors with hypermethylation (2.15 +/- 0.37, mean +/- SE) were significantly (P < 0.01) lower than those without hypermethylation (6.09 +/- 1.38), and LATS2 mRNA levels in breast tumors with hypermethylation (1.42 +/- 0.66) were also significantly (P < 0.01) lower than those without hypermethylation (3.10 +/- 1.00). The decreased expression of LATS1 or LATS2 mRNA was significantly associated with a large tumor size, high lymph node metastasis, and estrogen receptor and progesterone receptor negativity. Furthermore, the decreased expression of LATS1 mRNA, but not LATS2 mRNA, was significantly (P < 0.05) associated with a poor prognosis. CONCLUSIONS: Hypermethylation of the promoter regions of LATS1 and LATS2 likely plays an important role in the down-regulation of their mRNA levels in breast cancers, and breast cancers with a decreased expression of LATS1 or LATS2 mRNA levels have a biologically aggressive phenotype.

Adult↗

PubMed2005

Prediction of docetaxel response in human breast cancer by gene expression profiling.

PURPOSE: Docetaxel is one of the most effective anticancer drugs available in the treatment of breast cancer. Nearly half of the treated patients, however, do not respond to chemotherapy and suffer from side effects. The ability to reliably predict a patient's response based on tumor gene expression will improve therapeutic decision making and save patients from unnecessary side effects. PATIENTS AND METHODS: A total of 44 breast tumor tissues were sampled by biopsy before treatment with docetaxel, and the response to therapy was clinically evaluated by the degree of reduction in tumor size. Gene expression profiling of the biopsy samples was performed with 2,453 genes using a high-throughput reverse transcriptase polymerase chain reaction technique. Using genes differentially expressed between responders and nonresponders, a diagnostic system based on the weighted-voting algorithm was constructed. RESULTS: This system predicted the clinical response of 26 previously unanalyzed samples with over 80% accuracy, a level promising for clinical applications. Diagnostic profiles in nonresponders were characterized by elevated expression of genes controlling the cellular redox environment (ie, redox genes, such as thioredoxin, glutathione-S-transferase, and peroxiredoxin). Overexpression of these genes protected cultured mammary tumor cells from docetaxel-induced cell death, suggesting that enhancement of the redox system plays a major role in docetaxel resistance. CONCLUSION: These results suggest that the clinical response to docetaxel can be predicted by gene expression patterns in biopsy samples. The results also suggest that one of the molecular mechanisms of the resistance is activation of a group of redox genes.

Adult↗

PubMed2005

Cancer gene expression database (CGED): a database for gene expression profiling with accompanying clinical information of human cancer tissues.

Gene expression profiling of cancer tissues is expected to contribute to our understanding of cancer biology as well as developments of new methods of diagnosis and therapy. Our collaborative efforts in Japan have been mainly focused on solid tumors such as breast, colorectal and hepatocellular cancers. The expression data are obtained by a high-throughput RT-PCR technique, and patients are recruited mainly from a single hospital. In the cancer gene expression database (CGED), the expression and clinical data are presented in a way useful for scientists interested in specific genes or biological functions. The data can be retrieved either by gene identifiers or by functional categories defined by Gene Ontology terms or the Swiss-Prot annotation. Expression patterns of multiple genes, selected by names or similarity search of the patterns, can be compared. Visual presentation of the data with sorting function enables users to easily recognize of relationships between gene expression and clinical parameters. Data for other cancers such as lung and thyroid cancers will be added in the near future. The URL of CGED is http://cged.hgc.jp.

Databases, Genetic↗

PubMed2005

Usefulness of three-dimensional multidetector-row CT images for preoperative evaluation of tumor extension in primary breast cancer patients.

PURPOSE: Usefulness of three dimensional (3D) multidetector-row CT (MDCT) images for preoperative evaluation of tumor extension was studied in primary breast cancer patients. METHODS: 3D-MDCT tumor images of 143 tumors in 143 patients with primary breast cancer were created with the volume rendering method. The transverse tumor size (TS) and vertical tumor size (VS) were then measured in an anterior-posterior view of the 3D-MDCT images. The pathological tumor size was determined according to a map of the tumor spread prepared by pathologists using multi-sliced (3-5 mm intervals) surgical specimens and compared with the tumor size on 3D-MDCT images. RESULTS: First, the optimal method for creating 3D-MDCT tumor images was determined for the first 40 patients (learning set), resulting in a fairly good correlation of tumor size on 3D-MDCT images with pathological tumor size (r = 0.983 for TS and r = 0.958 for VS). We then carried out a validation study on the next 103 patients (validation set). The 3D-MDCT tumor size's strong correlation with the pathological tumor size demonstrated a high rate of accuracy (r = 0.974 for TS and r = 0.977 for VS). Subset analyses according to histological type showed that correlation coefficients were r = 0.979 for TS and r = 0.981 for VS of invasive ductal carcinomas (n = 88), r = 0.948 for TS and r = 0.970 for VS of ductal carcinomas in situ (n = 10), and r = 0.984 for TS and r = 0.976 for VS of invasive lobular carcinomas (n = 5). CONCLUSION: 3D-MDCT images can assess breast cancer tumor extension highly accurately, and thus seems to be useful for planning the extent of resection in breast conserving surgery.

Adult↗

PubMed2005

Possible involvement of aromatase overexpression induced by cyclo-oxygenase-2 in the pathogenesis of idiopathic gynecomastia.

The pathogenesis of idiopathic gynecomastia, which shows no imbalance in serum estrogens and androgens levels unlike gynecomastia of other causes, is unknown. It seems to be of interest to study the in situ aromatase expression in idiopathic gynecomastia to investigate a possible involvement of intratumoral biosynthesis of estrogens in the pathogenesis of this disease. The expression level of aromatase mRNA was studied by a real-time polymerase chain reaction (PCR) assay in four idiopathic gynecomastia cases (two florid type and two fibrous type). In addition, the proportion of promoter usage (promoters I.3 I.4, l. 7, and PII) of the aromatase gene was determined by PCR-gel electrophoresis. Localization of aromatase and cyclo-oxygenase-2 (COX-2) expression was studied by immunohistochemistry. The aromatase mRNA level of the florid type gynecomastia (3.05 and 1.66) was higher than that in the fibrous type (0.76 and 0.04). The proportion of promoter Pll in the florid type (94.1% and 84.8%) was very high as compared with that of the fibrous type (0.7% and 0.5%). Immunohistochemical studies have revealed that aromatase and COX-2 were strongly expressed in the duct epithelial cells in the florid type, but they were weak or negative in the fibrous type. COX-2 is suggested to upregulate aromatase expression by enhancing the transcription via promoter Pll in idiopathic gynecomastia of the florid type but not of the fibrous type. Because idiopathic gynecomastia initially develops as the florid type and regresses as the fibrous type, a high estrogen milieu induced by increased aromatase expression is speculated to play some role in the pathogenesis of idiopathic gynecomastia.

Adolescent↗

PubMed2005

Prediction of response to docetaxel by immunohistochemical analysis of CYP3A4 expression in human breast cancers.

BACKGROUND: Docetaxel (DOC) is inactivated by CYP3A4, high expression of which in tumor tissue might serve as a resistance mechanism. In the present study, the CYP3A4 protein level in breast cancers was determined by immunohistochemistry, and its relationship with the response to DOC treatment was studied. MATERIALS AND METHODS: Thirty-one patients with locally advanced (n = 21) or recurrent (n = 10) breast cancers underwent tumor biopsy, followed by DOC treatment (60 mg/m2 q3w). Expression of CYP3A4 was studied by immunohistochemistry. RESULTS: Patients with CYP3A4 negative tumors (n = 15) by immunohistochemistry showed a significantly (P < 0.01) higher response rate (67%) to DOC treatment than those with CYP3A4 positive tumors (n = 16, 19%). The positive predictive value, negative predictive value, and diagnostic accuracy of CYP3A4 expression by immunohistochemistry in the prediction of response to DOC were 67%, 81%, and 74%, respectively. CONCLUSION: Immunohistochemical analysis of CYP3A4 expression in tumor cells might be clinically useful in the prediction of tumor response to DOC.

Adult↗

PubMed2005

Three-dimensional ultrasound imaging of breast cancer by a real-time intraoperative navigation system.

BACKGROUND: In order to achieve a good cosmetic result without increasing the risk of ipsilateral breast cancer recurrence after breast conserving surgery, it is very important to minimize the resection volume of the breast without compromising the negativity of the surgical margin. For this purpose, it is necessary to obtain precise information on tumor extension. We therefore developed a three-dimensional (3-D) ultrasound navigation system for breast cancer surgery, which can be performed in the operating room just before surgery. METHODS: We obtained 3-D breast tumor images by the 3-D ultrasound navigation system in 40 patients with primary breast cancer (stage 0-II) who underwent mastectomy or breast conserving surgery. The tumor size was measured in a coronal view of the 3-D tumor image and compared with the tumor size obtained from a pathological map of the tumor extension. RESULTS: We obtained 3-D tumor images in 38 patients (success rate=95%). The tumor size in the images showed a very strong correlation with the pathological tumor size (r=0.898). The difference in tumor size between the 3-D images and pathology was less than 1 cm in 29 tumors (76.3%) and less than 2 cm in 36 (94.7%). On the other hand, the difference in tumor size between palpation and pathology was less than 1 cm in 19 out of 38 tumors (50.0%) and less than 2 cm in 29 tumors (76.3%). The absolute difference between the 3-D images and pathology was significantly less than that between palpation and pathology (p=0.0197). CONCLUSIONS: Our 3-D ultrasound navigation system is useful in visualizing breast tumor extension and is more accurate than palpation. The system is expected to be helpful in deciding on the appropriate surgical margin in breast cancer surgery, resulting in a better cosmetic outcome without increasing the risk of surgical margin positivity.

Adult↗

PubMed2005

[Cancer prevention].

The 12 th Oncology Forum discussed the progress and future strategy of cancer prevention in Japan. The National Cancer Center has established a research center for screening focusing on the most common six cancer, stomach, lung, liver, colon, breast and uterus cancer. The program so far had a cumulative detection rate of 3.3%, which is high,and may reflect the selection of subjects. Screening and chemoprevention is also being investigated in prostate cancer, but the issues centre on how to make this widely available. High risk subjects can also be identified for breast cancer. Obesity and family history are especially important. In colorectal cancer studies are evaluating different diets, but general application is not yet possible and the infrastructure to implement any general screening and prevention does not exist. Development of pharmaceutical treatments for prevention is difficult because of the need for very safe treatments, and also because of the length of time needed to carry out studies. Overall, cancer prevention is still in evolution. New approaches are needed, and new infrastructure will be needed at a government level to implement this.

Breast Neoplasms↗

PubMed2005

[The feasibility of FEC (75) as adjuvant chemotherapy for Japanese breast cancer patients].

Recently, high-dose FEC (fluorouracil, epirubicin, and cyclophosphamide) has been increasingly used in adjuvant chemotherapy for breast cancer in Japan. However, the safety and tolerability of high-dose FEC are not well evaluated in Japanese breast cancer patients. We studied the feasibility of FEC (75) (fluorouracil: 500 mg/m(2), epirubicin: 75 mg/m(2), and cyclophosphamide:500 mg/m(2), q 3 w, 6 cycles) as adjuvant chemotherapy for 59 primary breast cancer patients. Out of these patients, 56 (94.9%) finished 6 cycles-FEC. The mean epirubicin dose received was 431.7 mg/m(2) (95.9% of the intended dose of 450 mg/m(2)). Forty-five (76.2%) of 59 patients experienced neutropenia of grade 3 or 4, while the rates of febrile neutropenia (grade 3) and infection (grade 2) were 3.4% and 10.2%, respectively. Anemia (88.2%), fatigue (42.4%), nausea (40.6%), liver dysfunction (40.7%), and vomiting (18.7%) occurred, however most of them were mild and categorized into grade 1 or 2. No patients developed any cardiac failure symptoms. This study shows FEC (75) is well tolerable as adjuvant chemotherapy for Japanese breast cancer patients.

Adult↗

PubMed2004

Down-regulation of intratumoral aromatase messenger RNA levels by docetaxel in human breast cancers.

PURPOSE: The reason why chemotherapy induces resistance to subsequent hormonal therapy remains to be clarified in postmenopausal breast cancers. We hypothesized that chemotherapy might down-regulate the intratumoral biosynthesis of estrogens. Thus, we have studied the influence of chemotherapy (docetaxel) on intratumoral aromatase mRNA expression because aromatase is a key enzyme for intratumoral biosynthesis of estrogens. EXPERIMENTAL DESIGN: The mRNA levels of aromatase and its inducers [tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and cyclooxygenase 2 (COX-2)] were determined by a real-time polymerase chain reaction assay in breast cancer tissues obtained before and after neoadjuvant chemotherapy with docetaxel (four cycles of 60 mg/m2 every 3 weeks) in 16 postmenopausal patients with estrogen receptor (ER)- and/or progesterone receptor (PR)-positive breast cancers. ER and PR levels in tumor tissues were also determined by enzyme immunoassay before and after chemotherapy. RESULTS: The intratumoral aromatase mRNA levels decreased significantly (P < 0.05) after chemotherapy from 0.84 +/- 0.28 (mean +/- SE) to 0.47 +/- 0.28. The intratumoral TNF-alpha mRNA levels also decreased significantly (P < 0.05) after chemotherapy from 2.40 +/- 0.52 to 0.95 +/- 0.25. On the contrary, the intratumoral IL-6 and COX-2 mRNA levels showed a marginally significant increase (P = 0.07) and a significant increase (P < 0.05), respectively, after chemotherapy. PR levels showed a marginally significant decrease (P = 0.08) after chemotherapy, whereas ER levels were almost constant before and after chemotherapy. CONCLUSIONS: Antitumor activity of docetaxel is mediated, at least in part, through a down-regulation of aromatase expression in tumor tissues, resulting in the suppression of intratumoral estradiol synthesis. Aromatase expression seems to be regulated mostly by TNF-alpha, but not IL-6 and COX-2.

Aged↗

PubMed2004

Prognostic significance of intra-tumoral estradiol level in breast cancer patients.

Although the intra-tumoral estradiol (E2) level is thought to be more closely related to the E2-inducible events such as progesterone receptor (PR) induction and tumor growth than the serum E2 level, prognostic significance of the intra-tumoral E2 level in breast cancer patients has yet to be studied. E2 level in tumor tissues obtained from 90 primary breast cancer patients were measured by the high-pressure liquid chromatography-radioimmunoassay method. Relationship between the intra-tumoral E2 level and the various clinicopathological factors including the prognosis was investigated. E2-high tumors (n=45) were significantly more likely to be estrogen receptor (ER)-positive tumors and PR-positive tumors than E2-low tumors (n=45). A significant correlation was observed between the intra-tumoral E2 level and PR level by a simple curve fit test (r=0.39, P<0.01) in the ER-positive tumors. Univariate analysis showed that lymph node status, intra-tumoral E2 level, ER, and PR were significant prognostic factors, and multivariate analysis showed that only lymph node status and PR status were significant independent prognostic factors. PR is induced by E2 through ER in human breast cancers. PR, which warrants both the presence of functional ER and the enough level of intra-tumoral E2, can serve as a better prognostic factor than intra-tumoral E2 level or ER in primary breast cancer patients probably because PR is a better marker of estrogen-dependency of tumor growth than intra-tumoral E2 level or ER.

Adult↗

PubMed2004

Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression.

The Wilms' tumor gene WT1 is overexpressed in leukemias and various types of solid tumors, and the WT1 protein was demonstrated to be an attractive target antigen for immunotherapy against these malignancies. Here, we report the outcome of a phase I clinical study of WT1 peptide-based immunotherapy for patients with breast or lung cancer, myelodysplastic syndrome, or acute myeloid leukemia. Patients were intradermally injected with an HLA-A*2402-restricted, natural, or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses as the principal endpoints. Twenty-six patients received one or more WT1 vaccinations, and 18 of the 26 patients completed WT1 vaccination protocol with three or more injections of WT1 peptides. Toxicity consisted only of local erythema at the WT1 vaccine injection sites in patients with breast or lung cancer or acute myeloid leukemia with adequate normal hematopoiesis, whereas severe leukocytopenia occurred in patients with myelodysplastic syndrome with abnormal hematopoiesis derived from WT1-expressing, transformed hematopoietic stem cells. Twelve of the 20 patients for whom the efficacy of WT1 vaccination could be assessed showed clinical responses such as reduction in leukemic blast cells or tumor sizes and/or tumor markers. A clear correlation was observed between an increase in the frequencies of WT1-specific cytotoxic T lymphocytes after WT1 vaccination and clinical responses. It was therefore demonstrated that WT1 vaccination could induce WT1-specific cytotoxic T lymphocytes and result in cancer regression without damage to normal tissues.

Amino Acid Substitution↗

PubMed2004

Association of p53 genetic polymorphism (Arg72Pro) with estrogen receptor positive breast cancer risk in Japanese women.

Since it is well established that inactivation of p53 is involved in pathogenesis of breast cancer, it seems to be reasonable to assume that p53 genetic polymorphism at codon 72 (p53Arg72Pro) which affects the function of p53 might have an influence on breast cancer risk. Thus, in the present study, we have studied the association of p53Arg72Pro polymorphism with breast cancer risk. A case-control study was conducted with 191 breast cancer patients and 218 healthy female controls. p53Arg72Pro polymorphism was examined in their association with breast cancer risk after adjustment for the epidemiological risk factors. Relationship between p53Arg72Pro polymorphism and clinicopathological characteristics of breast cancers was also studied. In addition, frequency of somatic p53 mutation was compared according to the genotype of p53Arg72Pro polymorphism. p5372Pro/Pro homozygotes showed a significant increase in the risk of estrogen receptor (ER) positive breast cancer (adjusted odds ratio (OR) = 2.04, P = 0.04) as compared with p5372Arg/Arg homozygotes, whereas such an association was not found between p5372Pro/Pro homozygotes and ER negative breast cancer risk. Subset analysis according to menopausal status showed that p5372Pro/Pro homozygotes were significantly associated with ER positive breast cancer risk in postmenopausal women (adjusted OR = 3.42, P = 0.01) but not in premenopausal women. Frequency of ER positive tumors was significantly (p < 0.01) higher in breast cancer patients with p5372Pro/Pro genotype (82.8%) than those with p5372Arg/Arg genotype (54.5%). Mutational analysis of p53 in tumors showed that p5372Pro/Pro homozygotes had a lower frequency of p53 mutation (3.5%) than p5372Arg/Arg homozygotes (10.5%). It is suggested that p53Arg72Pro polymorphism is associated with ER positive breast cancer risk, especially, in postmenopausal women. The higher frequency of p53 somatic mutation in p5372Arg/Arg homozygotes than p5372Pro/Pro homozygotes is consistent with the thesis that the function of p5372Pro/Pro is impaired so that a further alteration of p53 gene is less required in p5372Pro/Pro homozygotes than p5372Arg/Arg homozygotes.

Adult↗

PubMed2004

Sentinel lymph node biopsy using periareolar injection of radiocolloid for patients with neoadjuvant chemotherapy-treated breast carcinoma.

BACKGROUND: The feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) for patients with breast carcinoma have been investigated primarily for the situation in which the radiocolloid imaging agent is injected peritumorally. No such study has involved periareolar injection of radiocolloid, although the usefulness of this injection technique has been demonstrated in patients with early-stage breast carcinoma who have not been treated with NAC. The objective of the current study was to determine the feasibility and accuracy of SLN biopsy using periareolar injection of radiocolloid for patients with breast carcinoma who were treated with NAC. METHODS: Forty-seven patients with AJCC Stage II or III breast carcinoma who were treated with NAC were enrolled in the study. All patients underwent SLN biopsy, which involved a combination of periareolar injection of radiocolloid (technetium 99m tin colloid) and peritumoral injection of isosulfan blue dye, followed by backup axillary lymph node dissection. SLN metastases were examined by hematoxylin and eosin staining and immunohistochemical analysis using an anticytokeratin antibody. RESULTS: An SLN was identified successfully in 44 patients (94%). Twenty-nine patients (66%) had positive SLNs. Fifteen patients had negative SLNs, and 4 patients had positive non-SLNs. Thus, the false-negative rate was 12.1% (4 of 33 patients). The false-negative rate tended to be higher, although not statistically significantly so, among patients who had clinically positive axillary lymph nodes before and/or after NAC (15.8%; 3 of 19 patients) compared with patients who had clinically negative axillary lymph nodes both before and after NAC (7.1%; 1 of 14 patients). CONCLUSIONS: SLN biopsy using periareolar injection of radiocolloid is feasible after NAC. In patients with clinically negative axillary lymph nodes both before and after NAC, SLN biopsy was capable of predicting axillary lymph node status with an accuracy comparable to the accuracy associated with SLN biopsy for patients with early-stage carcinoma who have not been treated with NAC.

Adult↗

PubMed2004

NY-ESO-1 expression and immunogenicity in malignant and benign breast tumors.

NY-ESO-1 is a cancer/testis antigen expressed in normal adult tissues solely in the testicular germ cells of normal adults and in various cancers. It induces specific humoral and cellular immunity in patients with NY-ESO-1-expressing cancer. The aim of this study was to determine the frequency of NY-ESO-1 mRNA and protein expression in malignant and benign breast tumors. NY-ESO-1 mRNA expression was detected by conventional reverse transcription-PCR and real-time PCR, and that of the protein expression by immunohistochemistry and Western blot analysis. Expression of NY-ESO-1 mRNA was detected in 37 of 88 (42%) cancer specimens, whereas that of the NY-ESO-1 protein was detected only in 1 mRNA-positive specimen. In the latter case, expression level of NY-ESO-1 mRNA relative to that in the testis was relatively high (75% of testicular expression) and to the other among breast cancer specimens. In benign breast lesions, 21 of 31 (68%) specimens expressed low levels of NY-ESO-1 mRNA. In 1 case of fibroadenoma, NY-ESO-1 mRNA was 8% of the testicular level, and protein was detected by Western blot analysis. Only 1 breast cancer patient had detectable antibody at time of surgery, which disappeared within 2 years. Tumor specimen from this patient was both NY-ESO-1 mRNA and protein positive, and NY-ESO-1-specific CD8 T cells were detected in this patient by IFN-gamma enzyme-linked immunospot assay using NY-ESO-1 recombinant adeno and vaccinia virus. A higher rate of NY-ESO-1 expression was noted in breast cancer with high histological grade and negative hormone receptor status, suggesting NY-ESO-1 as a potential tumor antigen for immunotherapy in patients with breast cancer and poor prognosis.

Adenoviridae↗