Biomedical subjects

H Inaji

Publications and source records attributed to H Inaji.

At least 37 records · Page 2Linked to original sources

PubMed1998

The Current Status of the Treatment of Ductal Carcinoma In Situ of Japanese Women, Especially Breast Conserving Operation in Relation to the Surgical Margin and Short Term Outcome.

The indications for a breast conserving operation in the treatment of ductal carcinoma in situ (DCIS) of the breast with clinical manifestations other than mammographically detected calcifications are controversial. A positive surgical margin has been suggested to be an improtant risk factor for local recurrence after a breast conserving operation. We attempted to clarify the frequency of positive surgical margins when performing breast conserving operations for DCIS, identify the risk factors for positive margins, and also to evaluate the short-term outcome. Between 1988 and 1992, 5571 breast cancer cases were surgically treated at the 7 institutions of the authors, of which 375 cases (6.7%) were histologically diagnosed as DCIS. The most frequent clinical manifestation was a tumor in 64% of the cases, followed by nipple discharge in 23% and calcification on mammography in 12%. Of these 375 cases, 242 cases were analyzed. Sixty-six cases had undergone a breast conserving operation. Axillary dissection was not performed in 29 cases. The median follow up period was 61.4 months. The initial surgical margin was positive in 29% of the cases. The most significant factor for a positive surgical margin was young age fllowed by large tumor size. There were four cases with local recurrence. Three recurrences developed in the same quadrant. All four cases remain alive after total mastectomy. There were no cases with distant metastasis or axillary recurrence. Breast cancerving operation for DCIS have shown satisfactory results to date, and when clear surgical margins can be obtained, this procedure, without axillary dissection, should be considered even for patients with clinical manifestations other than mammographically detected calcifications.

Journal Article↗

PubMed1998

Prognostic impact of urokinase-type plasminogen activator (PA), PA inhibitor type-1, and tissue-type PA antigen levels in node-negative breast cancer: a prospective study on multicenter basis.

Urokinase-type plasminogen activator (u-PA) is a key protease in cancer invasion and metastasis. Recent studies demonstrated that u-PA, plasminogen activator inhibitor type-1 (PAI-1), and tissue-type plasminogen activator (t-PA) are prognostic factors in breast cancer. However, there have been no prospective studies of node-negative breast cancer on a multicenter basis. On the other hand, some patients, even those with node-negative breast cancer, developed recurrence, and only tumor size is available as a predicting factor in this group. Therefore, it is necessary to find other prognostic factors in node-negative breast cancer to determine suitable adjuvant therapies. Tissue samples in this prospective study were obtained from 130 patients with node-negative invasive breast cancer who underwent radical operation at four hospitals. The median follow-up was 52.6 months. u-PA, PAI-1, and t-PA antigen levels were assayed by ELISA kits using the cytosolic fractions of tumors. Patients with high u-PA, high PAI-1, or low t-PA had significantly higher relapse rates than did those with low u-PA, low PAI-1, or high t-PA, respectively, by the Kaplan-Meier method (P = 0.006, 0.032, and 0.028, respectively). Analyses of the combinations of both u-PA and PAI-1 or both u-PA and t-PA showed that the differences in relapse rate between the high- and low-risk groups were statistically very significant. In the univariate analysis, u-PA, PAI-1, t-PA, progesterone receptor, and tumor size (T3 versus T1) were significantly correlated with relapse. However, the multivariate analysis revealed that only u-PA (P = 0.023) was an independent prognostic factor. This study showed that u-PA was a new significant independent prognostic factor in node-negative breast cancer.

Adult↗

PubMed1998

[Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.

Administration, Oral↗

PubMed1997

[Benefits of adjuvant chemotherapy for breast cancer].

The main therapy for primary breast cancer is not surgery, but a systemic therapy involving administration of cytotoxic chemotherapy or the use of ablative or additive endocrine therapy to control disseminated micrometastasis. The results of randomized trials and meta-analysis show that CMF, the standard adjuvant chemotherapy, is effective regardless of axillar lymph node involvement or menopausal status. Effectiveness of adjuvant chemotherapy with an anthracyclin-based regimen remains controversial. The trial by CUBC and NSAS-BC comparing UFT, widely used in the management of patients with breast cancer in Japan, with CMF is on-going.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Recent Progress in Breast Conserving Therapy: From Experiences in Japan.

Breast conserving therapy (BCT) was conducted in 22.1% of breast cancer patients in 1994 in Japan and is being performed with increasing frequency. According to the data already published, 10-27% of patients treated with BCT had a positive surgical margin. The recurrence rate in the breast is 1-2% annually, The 5-year overall survival in patients mostly consisting of stage I is 90% or higher at the present time. A case-control analysis of a multicenter study revealed that significant risk factors for breast recurrence were a positive surgical margin and absence of radiation therapy. Progress in basic research and diagnosis has also been instrumental in improving treatment results.

Journal Article↗

PubMed1996

Histologic characteristics of breast cancers with occult lymph node metastases detected by keratin 19 mRNA reverse transcriptase-polymerase chain reaction.

BACKGROUND: Amplification of keratin 19 mRNA (K19) by reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown to be a sensitive method to detect occult breast cancer metastases in lymph nodes. METHODS: Axillary lymph nodes were obtained from 126 patients with breast cancer, and metastases in these lymph nodes were studied by both histologic examination and K19 RT-PCR. The patients were categorized into 3 groups according to the results of these 2 examinations, i.e., patients with 1) both histologically and K19 RT-PCR negative lymph nodes (metastases negative group [n = 91]); 2) histologically negative but K19 RT-PCR positive lymph nodes (occult metastases positive group [ n = 15]); and 3) histologically positive lymph nodes (metastases positive group [n = 20]). RESULTS: Various histologic parameters such as tumor size, histologic type, histologic grade, lymphatic invasion, vascular invasion, and estrogen receptor status were compared among these three groups. There were no significant differences among any of these histologic parameters between the metastases positive and occult metastases positive groups. Conversely, tumor size of the metastases positive (2.5 +/- 0.2 cm) and occult metastases positive (2.5 +/- 0.2 cm) groups was significantly (P < 0.05) greater than that of the metastases negative group (1.9 +/- 0.1 cm), and positivity of lymphatic vessel invasion in the former 2 groups (70% and 53%, respectively) was also significantly (P < 0.01) greater than that in the latter group (18%). CONCLUSIONS: These results demonstrate that histologic characteristics of breast cancers with occult metastases are similar to those of breast cancers with histologically detectable metastases.

Actins↗

PubMed1996

Phyllodes Tumor of the Breast: Pathology, Histogenesis, Diagnosis, and Treatment.

Phyllodes tumor of the breast is histologically unique in that it is composed of epithelial and stromal components. The histogenesis of this disease has remained largely unknown but recently we have obtained interesting information through clonal analysis, and have been able to show a difference in the histogenesis between phyllodes tumor and fibroadenoma. Elucidation of histogenesis would difinitely improve our understanding of the biological behavior of this disease and also help to establish the most appropriate treatment strategy. The pathology, histogenesis, diagnosis, and treatment of phyllodes tumor are reviewed in this paper. Our hypothesis on the histogenesis of this disease is also presented.

Journal Article↗

PubMed1996

Demonstration of monoclonal origin of human parotid gland pleomorphic adenoma.

BACKGROUND: Parotid gland pleomorphic adenoma is histologically comprised of epithelial and mesenchymal elements. It remains to be established whether this neoplasm arises from epithelial and mesenchymal elements, or solely from the epithelial element. METHODS: In an attempt to resolve this issue, we have conducted clonal analysis on five pleomorphic adenomas. The method for clonal analysis was based on the trinucleotide repeat polymorphism of the x-chromosome-linked androgen receptor gene and on random inactivation of this gene by methylation. The epithelial and mesenchymal elements were obtained separately from the paraffin sections of the pleomorphic adenomas using a microdissection technique and then subjected to clonal analysis. RESULTS: Clonal analysis revealed that both epithelial and mesenchymal elements were monoclonal. In addition, the same allele of the androgen receptor gene was inactivated in both elements in every case. CONCLUSIONS: It is unlikely that the epithelial and mesenchymal elements of different origin happen to inactivate the same allele of the androgen receptor gene in all five tumors. Rather, it is more reasonable to consider that these two elements have a common single cell origin.

Adenoma, Pleomorphic↗

PubMed1996

Differential distribution of ErbB-2 and pS2 proteins in ductal carcinoma in situ of the breast.

We examined the expression of ErbB-2 and pS2 proteins in 59 ductal carcinoma in situ (DCIS) of the breast, either pure DCIS or DCIS associated with invasive carcinoma, using immunohistochemical staining of paraffin-embedded sections. Positive staining for ErbB-2 and pS2 proteins was noted in 32% (19/59) and 46% (27/59) of DCIS, respectively. An inverse relationship between ErbB-2 and pS2 status in DCIS was observed (p < 0.01). From the viewpoint of histological subtype, the prevalence of ErbB-2 protein expression was significantly higher in the comedo subtype than the cribriform-micropapillary subtype. The prevalence of immunoreactivity for ErbB-2 in solid subtype was intermediate between those of the other two groups. In contrast, the prevalence of pS2 expression was significantly lower in the comedo subtype than in the cribriform-micropapillary subtype. Again, the prevalence of pS2 protein expression in the solid subtype was intermediate between those of the other two subtypes. Our results suggest that DCIS is biologically heterogeneous with regard to such marker substances. This has possible implications for management of these lesions.

Biomarkers, Tumor↗

PubMed1996

Detection of breast cancer micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Comparison between MUC1 mRNA and keratin 19 mRNA amplification.

Usefulness of MUC1 mRNA and keratin 19 mRNA as a target of reverse-transcriptase polymerase chain reaction (RT-PCR) was compared in the detection of breast cancer micrometastases in axillary lymph nodes. RT-PCR amplification of MUC1 mRNA and keratin 19 mRNA was conducted using total RNA samples. RT-PCR products were stained with ethidium bromide and analyzed by agarose gel electrophoresis. Expression of both MUC1 mRNA and keratin 19 mRNA was detected by RT-PCR in a breast cancer cell line (MRK) and in all the 23 primary breast cancers but not in the control lymph nodes obtained from patients with benign diseases. A serial dilution study of MRK cells against normal lymph node cells has shown that detection sensitivity of MUC1 RT-PCR and keratin 19 RT-PCR were 1/10(5) and 1/10(6) (cancer/lymph node cells), respectively. Sixty-three axillary lymph nodes were obtained from 23 patients with primary breast cancer, and metastases in each lymph node were investigated by histological examination (hematoxylin and eosin sections) and RT-PCR method. In all 10 lymph nodes, which were histologically metastasis-positive, both MUC1 mRNA and keratin mRNA were detected by RT-PCR. Of the 53 histologically negative lymph nodes, 3 (6%) and 5 (9%) lymph nodes were found to express MUC1 mRNA and keratin 19 mRNA, respectively, indicating the presence of micrometastases which could be detected by RT-PCR but not by histological examination. These results demonstrate the usefulness of both MUC1 RT-PCR and keratin 19 RT-PCR in the detection of breast cancer micrometastases in lymph nodes, and also indicate the superiority of keratin 19 RT-PCR over MUC1 RT-PCR because of its higher detection sensitivity.

Axilla↗

PubMed1996

[Detection of breast cancer micrometastases in lymph nodes by amplification of keratin 19 mRNA with reverse-transcriptase polymerase chain reaction].

Keratin 19 mRNA reverse-transcriptase polymerase chain reaction (K 19 RT-PCR) was compared with histological examination in the detection of breast cancer micrometastases in axillary lymph nodes. Sixty-three axillary lymph nodes, which were obtained from 23 breast cancer patients, were bisected. One half was studied by conventional histological analysis of hematoxylin and eosin sections. Total RNA was extracted from the other half and subjected to K 19 RT-PCR. In all the ten lymph nodes, which were histologically metastasis-positive, K 19 mRNA was detected by RT-PCR. Of the 53 histologically negative lymph nodes, five (9%) lymph nodes were found to express K 19 mRNA, indicating the presence of micrometastases which could be detected by RT-PCR but not by a histological examination. These results demonstrate the usefulness of K 19 RT-PCR in the detection of breast cancer micrometastases in lymph nodes.

Axilla↗

PubMed1995

Progression of fibroadenoma to phyllodes tumor demonstrated by clonal analysis.

BACKGROUND: The histogeneses of fibroadenoma and phyllodes tumor of the breast appear to be closely related, but it is still unclear whether fibroadenoma can progress directly to phyllodes tumor. METHODS: This issue was studied by conducting clonal analysis of fibroadenoma and phyllodes tumors that were obtained sequentially from the same patient. One patient developed local recurrence of phyllodes tumor twice, and the other two patients each developed a phyllodes tumor after excision of a primary fibroadenoma. The method for clonal analysis was based on trinucleotide repeat polymorphism of the X chromosome-linked androgen receptor (AR) gene and on random inactivation of the gene by methylation. RESULTS: Clonal analysis revealed that all the three primary fibroadenomas were monoclonal and all four recurrent phyllodes tumors were also monoclonal in origin. In addition, the same allele of the AR gene was inactivated in fibroadenoma and phyllodes tumor(s) in each patient. The probability that phyllodes tumors of different origin happen to inactivate the same allele of the AR gene as fibroadenomas in every case is quite low. Rather, it is more reasonable to assume that the phyllodes tumor has the same origin as fibroadenoma. CONCLUSIONS: These results identified monoclonal fibroadenomas that can progress to phyllodes tumors.

Adult↗

PubMed1995

Clonal analysis of benign and malignant human breast tumors by means of polymerase chain reaction.

Clonal analysis was conduced on a variety of benign and malignant human breast tumors using the method based on restriction fragment length polymorphism (RFLP) of the X 120 chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. Breast carcinoma was shown to be monoclonal in origin, consistent with a somatic mutational theory. Precancerous lesions such as atypical ductal hyperplasia and multiple intraductal papilloma were also found to be monoclonal, indicating that certain genetic changes had been accumulated in these lesions. Solitary intraductal papilloma was found to be monoclonal. Since this tumor is composed of two types of cells, luminal epithelial cells and myoepithelial cells, it was suggested that the origin of solitary intraductal papilloma is a precursor cell which is capable of differentiating into both luminal and myoepithelial cells. The fact that fibroadenoma is polyclonal indicates that this tumor is not neoplasia but hyperplasia of a lobule. Epithelial component of phyllodes tumor was found to be polyclonal but stromal component was found to be monoclonal. Thus, phyllodes tumor is considered to be a neoplasm of stromal cells but not of epithelial cells.

Base Sequence↗

PubMed1995

Demonstration of polyclonal origin of giant fibroadenoma of the breast.

We have shown that fibroadenoma of the breast is polyclonal and that phyllodes tumour is monoclonal in origin. It is not known whether a giant fibroadenoma which is histologically identical to the more usual type of fibroadenoma but grows to be a huge mass, like a phyllodes tumour, is polyclonal or monoclona. Clonal analysis was conducted on the DNA samples extracted from the paraffin sections of a giant fibroadenoma resected from a 21-year-old woman. The method used was based on trinucleotide repeat polymorphism of the X-chromosome-linked androgen receptor gene and on random inactivation of the gene by methylation. Clonal analysis showed that the giant fibroadenoma and the adjacent normal breast tissue are polyclonal in origin. Although the term giant fibroadenoma has often been used interchangeably with the term benign phyllodes tumour, because of their similarity in clinical appearance, our present results demonstrate that a giant fibroadenoma is a polyclonal fibroadenoma that has attained an immense size and is different from the monoclonal phyllodes tumour.

Adult↗

PubMed1995

Detection of c-erbB-2 gene amplification in nipple discharge by means of polymerase chain reaction.

In a patient with non-palpable breast carcinoma, c-erbB-2 gene amplification was detected by means of polymerase chain reaction (PCR) in the small number of breast carcinoma cells present in nipple discharge. Amplification of the c-erbB-2 gene is more frequent in carcinoma in situ than in invasive types. Detection by a PCR-based method may help diagnose non-palpable breast carcinoma with nipple discharge. Since this gene amplification is related to high proliferation, it might provide useful preoperative information regarding intraductal carcinoma of comedo type and predict responses to chemotherapy.

Adult↗

PubMed1995

Prognostic significance of bone metastasis from breast cancer.

There is no established method for assessing the prognosis of patients with breast cancer and metastasis confined initially to bone. The medical records of 82 patients with breast cancer nad metastasis confined initially to bone were reviewed. The following variables were analyzed at the time when bone metastasis was first diagnosed, to determine their relationship to length of survival: distribution of metastatic bone lesions on bone scan, presence of radiographic osteosclerosis in metastatic bone lesions, menstrual status, and disease-free interval. Univariate and multivariate analyses revealed that the distribution of metastatic bone lesions and the presence of radiographic osteosclerosis in these lesions were significant predictors of survival. Premenopausal or late postmenopausal status, and longer disease-free intervals (> or = 24 months) or no disease-free intervals (Stage IV breast cancer and metastasis confined to bone at the time of cancer diagnosis) showed a trend, although not statistically significant, toward longer survival. Distribution of metastatic bone lesions on bone scan and the presence of radiographic osteosclerosis in metastatic bone lesions should be considered prognostic variables for patients with breast cancer and metastasis confined initially to bone.

Adult↗

PubMed1995

[Prognostic factors for breast cancer].

Recently, a variety of new prognostic factors for breast cancer have been advocated, although most of these studies are still preliminary. Until the results of definitive studies to evaluate the clinical usefulness of these new factors are obtained, it is practically relevant to plan a treatment schedule of breast cancer patients through classical prognostic factors such as tumor size, axillary lymph node status, histological grade, and estrogen/progesterone receptor status.

Breast Neoplasms↗

PubMed1994

The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction.

BACKGROUND: The development of a sensitive method for the detection of breast carcinoma micrometastases in axillary lymph nodes is reported. METHODS: The method was based on amplification of MUC1 mRNA, which encodes a core protein of polymorphic epithelial mucin, by a reverse transcriptase-polymerase chain reaction (RT-PCR). Total RNA, which was extracted from a breast carcinoma cell line (MCF-7), primary breast carcinomas, and axillary lymph nodes, was subjected to analysis of MUC1 mRNA expression by the RT-PCR method. RESULTS: MUC1 mRNA expression was detected by RT-PCR in MCF-7 cells and in all 15 primary breast carcinomas but not in control lymph nodes taken from patients with benign diseases. A serial dilution study revealed that MUC1 RT-PCR was a very sensitive method, detecting one MCF-7 cell per 1,000,000 lymph node cells. The detection sensitivity of MUC1 RT-PCR method was compared with that of immunohistochemical staining of an epithelial marker (polymorphic epithelial mucin). Fifty axillary lymph nodes were obtained from 15 patients with primary breast carcinomas, and metastasis in each lymph node was investigated by both methods. The immunohistochemical method demonstrated metastasis in nine lymph nodes, and MUC1 mRNA was detected in all of them. Of the 41 lymph nodes that were diagnosed to be devoid of metastasis by immunohistochemistry, MUC1 mRNA was expressed by 6 but not by the other 35, indicating the presence of micrometastases in these 6 lymph nodes that could be detected only by the MUC1 RT-PCR method. CONCLUSIONS: The MUC1 RT-PCR method is more sensitive than immunohistochemistry for the detection of micrometastases in axillary lymph nodes. This new method would be of practical value in selecting the patients at high risk for relapse from those who are histologically lymph node negative.

Axilla↗