Biomedical subjects

Hitoshi Tsuda

Publications and source records attributed to Hitoshi Tsuda.

67 records · Page 4Linked to original sources

PubMed2002

Early invasive adenocarcinoma of the uterine cervix: criteria for nonradical surgical treatment.

OBJECTIVE: This retrospective study was undertaken to identify selection criteria for nonradical surgery for early invasive adenocarcinoma of the uterine cervix. METHODS: Seventy-nine patients with surgically treated cervical adenocarcinomas (with invasion to 5 mm or less) were examined clinicopathologically. The evaluation of stromal invasion was conducted according to the FIGO (1995) staging system. RESULTS: The mean age was 46 (range: 29-73) years, and the median follow-up was 118 (9-348) months. Definitive treatment modalities included radical hysterectomy in 71 (89.9%) cases, modified radical hysterectomy in 2 (2.5%), and simple extrafascial hysterectomy without pelvic lymphadenectomy in 6 (7.6%). Postoperative adjuvant external radiation therapy was given to 5 (6.3%) patients. The histological subtypes were endocervical in 37 (46.8%) cases, endometrioid in 32 (40.5%), and adenosquamous in 10 (12.7%). Forty-one (51.9%) patients had lesions with up to 3 mm of stromal invasion; of these, 24 (58.5%) had lesions with up to 7 mm of horizontal extension (stage IA1). Thirty-eight (48.1%) patients had lesions with stromal invasion greater than 3 mm and no greater than 5 mm; of these, 4 had lesions with no wider than 7 mm of horizontal extension (stage IA2). Of 73 patients with pelvic lymphadenectomy, one (1.4%) tumor (depth: 5 mm; width: 15 mm) had node metastases. Parametrial involvement was present in one (1.4%) patient (lesion depth: 5 mm; lesion width: 16 mm). None had adnexal metastasis. Eighty-eight percent of the patients with stromal invasion up to 3 mm had well-differentiated adenocarcinoma, compared to 53% of the patients with lesions invading more than 3 mm. Of all of the patients, 5 (6.3%) patients who received curative radical hysterectomies had recurrences and died. Among 5 patients, one patient with central pelvic recurrence had a lesion invading to a depth of 3 mm and width of 7 mm, and the others had lesions with more than 3 mm of invasion and 15 to 36 mm of width. CONCLUSIONS: Patients with early invasive adenocarcinoma to a depth of 3 mm or less stromal invasion, including those who meet the criteria for FIGO stage IA1, may be treated with simple extrafascial hysterectomy without lymphadenectomy and oophorectomy.

Adenocarcinoma↗

PubMed2002

Histological and immunohistochemical analysis of apocrine breast carcinoma.

BACKGROUND: There are few data regarding the biological characteristics of apocrine breast carcinoma in the literature due to its rarity and controversy over its definition. We analyzed the histopathological characteristics and tumor biology of apocrine breast carcinomas with regard to histological grade, p53, HER2, bcl-2, MIB-1 and hormone receptor status. PATIENTS AND METHODS: A consecutive series of 24 female apocrine breast carcinoma patients were the primary source of these retrospective data. Background factors including histological grade, nodal status and lymphatic invasion by tumor cells were analyzed. Immunohistochemical staining for p53, HER2, MIB-1, bcl-2, estrogen receptor (ER) and progesterone receptor (PR) was carried out on formalin-fixed, paraffin embedded specimens. RESULTS: Older age and postmenopausal status were observed more frequently in patients with apocrine breast carcinoma than those with invasive ductal carcinoma. Apocrine breast carcinoma also showed relatively lower histological grade than invasive ductal carcinoma. Nuclear accumulation of p53, HER2 overexpression, bcl-2 and MIB-1 index were observed in 29% (7/24), 33%(8/24), 25%(6/24) and 29% (7/24) of cases, respectively. Positivity for ER and PR was present in 17% (4/24) and 17% (4/24) of cases, respectively. CONCLUSIONS: Apocrine breast carcinoma tended to show low MIB-1 index, low bcl-2 expression and low positive rate of hormone receptors. There was no correlation between the three types of apocrine carcinoma and the positivity rate of p53, HER2, bcl-2, MIB-1 and hormone receptor status.

Adult↗

PubMed2002

Concordance in pathological response to neoadjuvant chemotherapy between invasive and noninvasive components of primary breast carcinomas.

BACKGROUND: Invasive breast carcinomas are composed of invasive and noninvasive components in varying proportions and sometimes the two components show different histopathological responses to chemotherapy, however there has been no study as yet comparing the pathological response to chemotherapy of invasive and noninvasive components. PATIENTS AND METHODS: A consecutive series of 100 women neoadjuvant chemotherapy with doxorubicin and docetaxel every three weeks before surgery. After the chemotherapy, surgically resected specimens were studied histologically according to the criteria of the Japanese Breast Cancer Society. RESULTS: Five cases (5/100; 5%) were determined to show Grade 3 pathological response, and 28 cases (28/100; 28%) showed Grade 2 response. There were 6 Grade 3 (6/96; 6%) and 18 Grade 2 (18/96; 19%) invasive component cases. There were 7 Grade 3 (7/82; 9%) and 18 Grade 2 (18/82; 22%) cases showing pathological response in the noninvasive component. With regard to pathological response, there was a strong correlation between the invasive and noninvasive components (p<0.001). There was also a correlation in pathological response between the invasive component and axillary lymph nodes in individual cases (p=0.02). There was no correlation between the response of the noninvasive component and axillary lymph nodes. By multivariate analysis, the overall primary tumor response was reflected by the histological response of the invasive component in the primary breast carcinoma. CONCLUSION: We suggest that the pathological response of the invasive component of breast carcinoma should be evaluated, which might provide more accurate information for prognosis and treatment decisions.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Histological grade, p53, HER2 and hormone receptor status of synchronous bilateral breast carcinoma.

BACKGROUND AND OBJECTIVES: Histological grade and tumor biology remain important predictors of the clinical behavior of breast carcinomas. We analyzed the clinicopathological characteristics and tumor biology with regard to histological grade (HG), p53, HER2 and hormone receptor status to address this question. PATIENTS AND METHODS: A consecutive series of 74 female synchronous bilateral breast carcinoma patients treated at the National Cancer Center Hospital were the primary source of these retrospective data. Clinicopathological background factors, histological grade and immunohistochemical staining for p53, HER2 and hormone receptor status, were analyzed. RESULTS: Of 148 synchronous bilateral tumors, 102 were invasive ductal carcinoma (IDC). The others included 24 pure or predominant ductal carcinoma in situ (DCIS), 5 spindle cell carcinomas, 16 invasive lobular carcinomas and 1 squamous cell carcinoma. 128 cases (128/148: 89%) were HG 1 (72/148: 49%) or HG 2 (56/148: 38%). The positivity rates for p53, HER2, estrogen receptor (ER) and progesterone receptor (PR) were 9%(14/148), 18%(26/148), 64%(95/148) and 64%(95/148), respectively. CONCLUSION: Our findings indicate that synchronous bilateral breast carcinomas showed a higher frequency of invasive lobular carcinoma, lower HG and higher rate of hormone receptor positivity than unilateral breast carcinomas.

Adult↗

PubMed2002

Correlation of DNA hypomethylation at pericentromeric heterochromatin regions of chromosomes 16 and 1 with histological features and chromosomal abnormalities of human breast carcinomas.

Changes in DNA methylation status are not only important for regulating gene expression but are also suggested to induce chromosome instability. To reveal the correlation of DNA methylation status in heterochromatin regions with tumor histology and with chromosome alterations, DNA methylation status was examined by Southern blot analysis, and numerical and structural chromosome alterations, including the formation of der(16)t(1;16)/der(1;16), were examined by fluorescence in situ hybridization at the two loci in the pericentromeric satellite 2 regions of chromosomes 16 and 1 in 39 human breast carcinomas. DNA hypomethylation at the D16Z3 and the D1Z1 loci was detected in 31% (12 of 39) and 36% (12 of 33) of carcinomas, respectively, and mostly concurred. DNA hypomethylation was more frequent in the carcinoma group of more aggressive histological types or grade 3 than in the carcinoma of less aggressive histological types or grades 1 and 2, and tended to be more frequent in carcinomas with > or =4 copies of chromosomes 16 and/or 1 than in carcinomas with < or =3 copies of any of these chromosomes. The frequency of DNA hypomethylation at the D16Z3 and the D1Z1 loci was 45% (10 of 22) and 53% (9 of 17) in carcinomas without der(16)t(1;16)/der(1;16), formation, but only 12% (2 of 17) and 19% (3 of 16) in carcinoma with der(16)t(1;16)/der(1;16), respectively (P = 0.036 and 0.070). The 16q breakage was almost equally detected between carcinoma groups with and without the DNA hypomethylation. DNA hypomethylation in the satellite 2 regions was suggested to be associated with the accumulation of a large number of numerical chromosome alterations and involved in the development of breast carcinomas of aggressive histological features. On the contrary, chromosome instability induced by mechanisms other than DNA hypomethylation in heterochromatin regions might cause the formation of der(16)t(1;16)/der(1;16) and less aggressive breast carcinomas.

Breast Neoplasms↗

PubMed2002

Evaluation of interobserver agreement in scoring immunohistochemical results of HER-2/neu (c-erbB-2) expression detected by HercepTest, Nichirei polyclonal antibody, CB11 and TAB250 in breast carcinoma.

To examine interobserver reproducibility in the judgments of HER-2/neu (c-erbB-2) oncoprotein expression, HER-2/neu expression was scored immunohistochemically. A total of 106 breast carcinomas were independently scored by five or six pathologists, using four commercially available anti-bodies (HercepTest, Nichirei polyclonal antibody, CB11 and TAB250). Two systems were used for the evaluation. In the Dako system, the intensity of membrane staining was primarily evaluated whereas in the Tohoku system, the area of the membrane-staining-positive cells was primarily evaluated. All four antibodies gave excellent concordance rates among the pathologists' judgments of the scores. Using the HercepTest and Nichirei polyclonal antibody, dividing the cases into two groups designated score 3+ and score 0/1+/2+ achieved a higher percentage of concordant cases than division into groups designated score 2+/3+ and score 0/1+. Using the HercepTest, the Dako system tended to achieve higher concordance than the Tohoku system. Conversely, CB11 and TAB250 showed similar concordance rates under both the Dako and the Tohoku systems, regardless of how the cases were divided. High interobserver agreement levels were achieved only when HER-2/neu overexpression was defined as a score of 3+, using any of the antibodies; these were similar between the Dako system and the Tohoku system. Positivity by TAB250 was lower than that by CB11. Using the HercepTest and Nichirei polyclonal antibody, cases with a score of 3+ almost always achieved complete interobserver agreement and showed HER-2/neu gene amplification. Conversely, cases with a score of 2+ achieved a low percentage of interobserver agreement and showed no gene amplification. Because judgment of a case as score 2+ was not very reproducible, and a score of 3+ was of biological significance and had high interobserver reproducibility, we suggest that only a score of 3+ be considered as overexpression. When cases of score 2+ are entered into a protocol, evaluation should be given by multiple observers and/or by using other tests such as fluorescence in situ hybridization.

Antibodies, Monoclonal↗

PubMed2002

Invasive ductal carcinoma associated with tubular adenoma of the breast.

We report an extremely rare case of the colocalization of a tubular adenoma and an invasive ductal carcinoma occurring in a 55-year-old woman. Following radiographical evaluation, fine-needle aspiration cytology of the left breast tumor was undertaken. Because cytological examination revealed malignancy, a partial mastectomy was performed. Histologically, the tumor (measuring 1.7 x 1.3 cm) comprised two distinct parts: tubular adenoma and invasive ductal carcinoma. The invasive ductal carcinoma showed a solid pattern, high nuclear and structural atypia and frequent mitotic figures, while the tubular adenoma consisted of a proliferation of small ducts lined by single layers of epithelial and myoepithelial cells with bland nuclei and inconspicuous nucleoli. The histological boundary was clearly defined between the tubular adenoma and the invasive ductal carcinoma, and between the tubular adenoma and the surrounding breast tissue. The current case might be a collision between separate tubular adenoma and invasive ductal carcinoma, but the malignant transformation of a tubular adenoma cannot be ruled out. Both the long-term observation of this case and analysis of more cases may enable us to determine the histological characteristics and clinical significance of invasive ductal carcinoma associated with tubular adenoma.

Adenoma↗

PubMed2002

Promoter hypermethylation and post-transcriptional mechanisms for reduced BRCA1 immunoreactivity in sporadic human breast cancers.

BACKGROUND: Germline mutation of BRCA1 is well known to cause familial breast cancer. Although somatic mutations of the BRCA1 gene are rare in sporadic breast cancers, a high incidence of reduced BRCA1 immunoreactivity has been demonstrated. As one of the mechanisms for this, gene silencing by hypermethylation of the BRCA1 promoter region has been reported. Here, we show the presence of a post-transcriptional mechanism by examining promoter hypermethylation, mRNA expression levels and immunoreactivity of BRCA1 in sporadic human breast cancers METHODS: Paired samples of 20 invasive ductal carcinomas and one invasive lobular carcinoma were obtained from sporadic breast cancer cases. The BRCA1 protein expression levels were determined by immunohistochemistry using a well-characterized antibody. The methylation status of the BRCA1 promoter region was determined by sequencing after bisulfite modification. The mRNA expression levels were determined by semi-quantitative reverse transcription polymerase chain reaction (PCR). Mutations in the entire BRCA1 coding region were analyzed by PCR single-strand conformation polymorphism analysis. RESULTS: Reduced immunoreactivity was observed in 13 of the 21 cancers. Hypermethylation was observed in five of the 13 cancers with reduced immunoreactivity and mRNA expression was almost absent in these five cancers. In the remaining eight cancers, mRNA expression was not decreased. None of the 21 cancers examined harbored BRCA1 mutations. CONCLUSION: These findings showed that post-transcriptional mechanisms, such as low efficiency of translation or reduced stability of BRCA1 protein, are also involved in reduced BRCA1 immunoreactivity in sporadic breast cancers.

Adult↗

PubMed2002

Clinically useful detection criteria for sentinel nodes in patients with breast cancer using a radioisotope technique.

BACKGROUND: The radioisotope technique has been used to identify sentinel nodes in patients with breast cancer. However, quantitative analysis of the radioactivity for detecting the sentinel nodes was not previously examined. In this study, we considered a clinically useful criterion for detecting sentinel nodes by a detailed analysis of 312 sentinel nodes using the radioisotope technique. PATIENTS AND METHODS: Patients with T1-2, N0 breast cancer were eligible for this study. The nodes with the highest radioactivity after injection of technetium-labeled tin colloids were identified as hot nodes. The radioactivities of the hot nodes and the background counts of the axillary basin were examined in order to establish new criteria for detecting the sentinel nodes. RESULTS: Between May 1997 and December 2001, 312 hot nodes were detected in 183 of 186 patients (98.4%). Since the false-negative rate for metastasis in hot nodes was only 2.1% (1/48), they could serve as sentinel nodes to predict the nodal status. However, there was a wide distribution of the hot nodes and the background in terms of absolute counts and a criterion for the sentinel nodes could not be established in terms of the absolute counts. When we adopted the criterion of sentinel nodes with a >/=100 count ratio in relation to the background, only 169 hot nodes (54.3%) met our definition. When the criterion of a >or=10 count ratio was adopted, all hot nodes met our definition and all other nodes remained non-sentinel nodes. CONCLUSION: The criterion for defining sentinel nodes in our method is a node with a >or=10 count ratio with respect to the background. It is recommended that an analysis based on such objective data should be investigated in order to provide surgeons with more accurate and clinically useful criteria for detecting sentinel nodes.

Adult↗

PubMed2002

Allelotype analysis of common epithelial ovarian cancers with special reference to comparison between clear cell adenocarcinoma with other histological types.

Determination of the histological type of epithelial ovarian cancer is clinically important to predict patient prognosis. To estimate accurately the chromosomal regions that frequently show loss of heterozygosity (LOH) in each histological type, LOH at 55 loci on 38 chromosomal arms was examined by means of laser capture microdissection and PCR-LOH analysis in 45 epithelial ovarian cancers composed of clear cell adenocarcinoma (CCA), serous adenocarcinoma (SEA), endometrioid adenocarcinoma (EMA) and mucinous adenocarcinoma (MUA). In addition, p53 (exons 5 - 8) gene mutations and the nuclear immunoreactivity of p53 proteins in these tumors were examined by PCR-SSCP and immunohistochemistry. In CCA, LOH was detected primarily on 1p (69%) followed by 19p (45%) and 11q (43%). On the other hand, in SEA, LOH was detected in at least 50% of cases on 1p, 4p, 5q, 6p, 8p, 9q, 12q, 13q, 15q, 16p, 17p, 17q, 18p, 18q, 19p, 20p and Xp. The incidences of LOH on 5q, 12q, 13q and 17p were significantly lower in CCA than in SEA (P = 0.019, 0.031, 0.0035 and 0.012). EMA showed a tendency for frequent LOH on 7p, whereas MUA showed significantly high occurrence of LOH at 17p13.1. The incidences of p53 mutation and p53 nuclear immunoreactivity also differed between CCA and SEA: 0% and 7% in the former and 64% and 45% in the latter (P = 0.0006 and 0.039). These findings clarify that there are differences in LOH distribution patterns among different histological subtypes of epithelial ovarian cancer. In CCA, p53 tumor-suppressor gene (TSG) is not involved in carcinogenesis and tumor-suppressor genes located on 1p are considered to play an important role in tumor development.

Adenocarcinoma, Clear Cell↗

PubMed2002

[Molecular diagnosis of breast cancer].

Alterations in protooncogenes and tumor-suppressor genes at the DNA and/or protein level indicate the biological properties of individual breast cancers. Information on these genetic and protein alterations is considered to be useful diagnostically and these alterations are now being applied in routine diagnosis or are under investigation for diagnostic application in the areas of: 1) determination of indications for specific therapies for advanced or metastatic breast cancers; 2) prediction of the response of primary tumors to adjuvant or neoadjuvant systemic therapies; and 3) identification of patient groups at high or low risk of recurrence from node-negative breast cancer.

Breast Neoplasms↗

PubMedDate not supplied

Immature glandular features in squamous cell carcinoma of the uterine cervix as an independent indicator of resistance to radiotherapy.

The aim of this study was to evaluate the significance of "immature glandular features" in cervical squamous cell carcinoma (SCC) as an indicator of tumor radioresistance. Pretreatment biopsied tissue specimens of cervical SCC from 100 patients who were uniformly treated with radiotherapy alone were classified into clinically radioresistant (cR) and radiosensitive (cS) groups. Seven histologic parameters comprising glassy cells, signet ring cells, squamous differentiation, recognizable gland, nuclear atypia, stromal response, and mitotic counts were examined. Glassy cells and signet ring cells were regarded as "immature glandular features". The correlation of these seven parameters with tumor response to radiotherapy and patient prognosis was analyzed by univariate and multivariate analyses. As objective indicators of glandular differentiation, alcian-blue staining and immunostaining of cytokeratins 7 and 20 were also performed. It was revealed that immature glandular features, absence of squamous differentiation, and low nuclear atypia were significant indicators of radioresistance of the tumor and of poorer patient prognosis. Combining those histological parameters, the present SCC cases were classified into 26 pathologically radioresistant (pR) and 74 radiosensitive (pS) groups. In the pR group, 54% (14 of 26) were clinically radioresistant, whereas 20% (15 of 74) of the pS group were clinically radioresistant (P = 0.002). The overall prognosis of the pR group was much poorer than that of the pS group (P < 0.0001). This correlation also held true in cases of identical stage and age. We could not show objectively glandular differentiation of "immature glandular features". Nonetheless, the identification of "immature glandular features" was effective in predicting the radiotherapy resistance of cervical SCC and poorer patient prognosis.

Adult↗

PubMedDate not supplied

Invasive ductal carcinoma of the breast with a large central acellular zone associated with matrix-producing carcinoma.

Matrix-producing carcinoma is a variant of metaplastic carcinoma of the breast that consists of overt carcinoma with direct transition to a cartilagenous and osseous stromal matrix. A clinicopathological association between MPC and high-grade invasive ductal carcinoma with a large central acellular zone has been recently discussed. However, few reports have ever shown the radiological, pathological and immunohistochemical correlation of this unique tumor. We present a case of 27-year-old woman with matrix-producing carcinoma with a large central acellular zone, which was characterized by a large homogeneous hypodense center with well-marginated, ring-like enhancement on contrast enhanced computerized tomography.

Adult↗