Expression of cytokeratin 19 in cytologic specimens of thyroid.
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Adenocarcinoma, Follicular↗
Biomedical subjects
H Sonoo
Publications and source records attributed to H Sonoo.
Changes of expression level of the differentiation markers in papillary thyroid carcinoma under thyrotropin suppression therapy in vivo immunohistochemical detection of thyroglobulin, thyroid peroxidase, and thyrotropin receptor.
BACKGROUND AND OBJECTIVES: Differences in the expression levels of Thyroglobulin (Tg), Thyroid peroxidase (TPO) and thyrotropin receptor (TSH-R) in primary and recurrent specimens under a suppressive serum TSH condition were elucidated in 26 papillary carcinoma patients. METHODS: Immunohistochemical detection was performed by use of each monoclonal antibody against Tg, TPO, and TSH-R. The staining concentrations of the three markers in each specimen were measured for comparison. RESULTS: The mean staining concentrations of Tg, TPO, and TSH-R in the entire primary tumor were 103.92, 104.6 and 89.25, respectively. Five cases showed stronger expression of all the differentiation markers and eight cases showed weaker expression of all these markers in recurrent tissue than in primary tumors. The weaker expression of TSH-R at the recurrent site as compared with that at the primary site significantly demonstrated the shortness of the disease free interval or overall survival. There were significant differences between the death due to cancer and the weaker expression of TSH-R in the recurrent tumor as compared with that in the primary tumor. CONCLUSIONS: Under the TSH suppressive condition, the markers were not expressed uniformly among recurrent tumors. Even under that state, however, low expression of TSH-R in the recurrent tissue was strongly related to a poorer outcome in the patients.
Adult↗
Predictive factors for response to endocrine therapy in patients with recurrent breast cancer.
Predictive markers and variables for response to anticancer therapy provide cancer patients with refinement of therapeutic options and a decreased likelihood of receiving an ineffective therapy. The best-established predictive marker for response to endocrine therapy for breast cancer is the status of estrogen receptors (ER) in the primary breast tumor. However, although patients with ER-positive tumors have a greater than 50% objective response rate to endocrine therapy, other patients can not obtain an objective response. Therefore additional markers, such as better molecular biologic markers, are needed. Our previous study using multivariate analysis revealed that the ER status of primary tumors and the dominant site of metastasis are independent predictors for response to first-line endocrine therapy and that a response to first-line endocrine therapy is only an independent predictor for response to second-line endocrine therapy. However, all these factors are already well-established predictive markers for response to endocrine therapy. Recently, a number of new hormonal agents, such as more selective aromatase inhibitors and specific antiestrogens, have been developed and introduced. However, several questions, such as the best sequences when using hormonal agents, remain to be elucidated. On the other hand, several molecular biologic markers predicting response to endocrine therapy, such as the expression of the HER family of tyrosine kinase receptors, pS2, Bcl-2, and vascular endothelial growth factor, have been reported. To elucidate the most effective use of endocrine therapy for recurrent breast cancer, classical and new predictive factors for response to endocrine therapy are reviewed, and the clinical implications of these factors are discussed.
Antineoplastic Agents, Hormonal↗
Endocrine options for breast cancer treatment: looking beyond tamoxifen.
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Anastrozole↗
Interstitial brachytherapy for recurrent breast cancer using a high dose rate Ir-192 remote afterloading system: a report of two cases.
We employed interstitial brachytherapy using a high dose rate Ir-192 remote afterloading unit in two breast cancer patients with locoregional recurrence. In the first case, skin metastasis was treated, with favorable control of the infield tumor but subsequent persistent sequelae and multiple outfield metastases. This experience caused us to be cautious when choosing brachytherapy for the second case, in whom a solitary metastasis to an axillary lymph node was successfully treated. Although this method is still investigational, it may play a critical role in the treatment of locoregional recurrence resistant to other treatment modalities.
Adenocarcinoma↗
The prognostic value of quality-of-life scores: preliminary results of an analysis of patients with breast cancer.
This study was conducted to elucidate the prognostic value of patient-assessed quality-of-life (QL) scores in cancer patients. QL was assessed in 47 consecutive patients with advanced or end-stage breast cancer using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD). The data collected from 19 of the 47 patients, who completed QL questionnaires more than twice before dying of cancer, were analyzed. The relationships between the QL scores and subsequent survival were examined at two assessment points, being the first and last assessment points of each of the 19 patients; corresponding respectively to median survival times of 14 and 4 months. The prognostic significance of the changes in QL scores that occurred over 3 months before the last assessment point was also examined. At the last assessment point, the scores of the physical aspects of QL were significantly related to survival. The change in scores of both overall QL and the physical aspects of QL were also significant predictors of survival. On the other hand, neither the scores nor the change in scores of the psychological and social aspects of QL was significant. This study indicates that both QL scores and changes in QL scores are promising prognostic predictors.
Adult↗
Immunohistochemical analysis of Ki-67, p53, p21, and p27 in benign and malignant apocrine lesions of the breast: its correlation to histologic findings in 43 cases.
We examined Ki-67, p53, p21, and p27 immunolocalization in 43 cases of apocrine lesions of the breast and correlated these findings with histologic parameters to understand their biologic significance. Twenty cases were benign, 1 case was borderline, and 22 cases were diagnosed as malignant, including 9 intraductal and 13 invasive apocrine carcinomas. Both the ratio of Ki-67-positive cases (17 of 21 [88.9%] versus 1 of 19 [5.3%]; P < .001) and the Ki-67 labeling index of positive cases examined (15.0% versus 2.7%; P < .005) were significantly higher in malignant than in benign apocrine lesions. None of the benign or borderline cases was immunohistochemically positive for p53, but 15 of 22 malignant cases (68.2%) demonstrated p53 (P < .001). In addition, the ratio of p53-positive cases was significantly higher in high nuclear grade cases (11 of 13 [84.6%]) than in intermediate nuclear grade cases (4 of 9 [44.4%]; P < .05). P53 immunoreactivity was also positively correlated with the nuclear grade of carcinoma cases examined in this study. Neither p21 nor p27 demonstrated any correlation with histologic parameters or findings of the apocrine lesions. Results of these studies suggest that Ki-67 and p53 may be good markers for differentiation between benign and malignant breast apocrine lesions.
Apocrine Glands↗
Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2.
Anti-oestrogen is effective for the treatment of oestrogen receptor (ER)-positive breast carcinomas, but most of these tumours become resistant to anti-oestrogen. It has been suggested that anti-oestrogen therapy may induce a HER2 signalling pathway in breast cancer cells and this may cause resistance to anti-oestrogen. Thus, it is conceivable that combined therapy with anti-oestrogen and anti-HER2 antibody might be more effective. In the present study, we investigated the effect of combined treatment with a humanized anti-HER2 monoclonal antibody, rhumAbHER2 (trastuzumab), and an anti-oestrogen, ICI 182,780, on the cell growth of three human breast cancer cell lines which respectively express different levels of ER and HER2. The combined treatment enhanced the growth inhibitory effect on ML-20 cells, which express a high level of ER and a moderate level of HER2, but showed no additive effect on either KPL-4 cells, which express no ER and a moderate level of HER2, or MDA-MB-231 cells, which express no ER and a low level of HER2. It is also suggested that both the antibody and anti-oestrogen induce a G1-S blockade and apoptosis. These findings indicate that combined treatment with anti-HER2 antibody and anti-oestrogen may be useful for the treatment of patients with breast cancer expressing both ER and HER2.
Antibodies, Monoclonal↗
Paradoxical hormone responses of KPL-1 breast cancer cells in vivo: a significant role of angiogenesis in tumor growth.
In our previous study, the growth of KPL-1 human breast cancer cells was found to be stimulated by an antiestrogen, ICI 182, 780, and inhibited by 17 beta-estradiol (E2) in vivo but not in vitro. To investigate the action mechanisms of these paradoxical responses, the effects of E2, ovariectomy (Ovex) and medroxyprogesterone acetate (MPA) on the growth, angiogenesis, apoptosis and expression of vascular endothelial growth factor (VEGF) were investigated. E2 stimulated the growth of KPL-1 cells but MPA inhibited it in vitro. In contrast, E2 propionate inhibited the growth of KPL-1 cells in female nude mice but Ovex and MPA stimulated it. E2 propionate suppressed angiogenesis and increased apoptosis in KPL-1 tumors, but Ovex and MPA promoted angiogenesis and decreased apoptosis. Both mRNA expression and secretion of VEGF were stimulated by MPA in KPL-1 cells, but in E2-dependent ML-20 cells they were both inhibited by MPA. E2 did not significantly influence VEGF expression in either cell line. These findings suggest that the abnormal modulation of VEGF expression by MPA and of the other angiogenic factor by E2 are responsible for the paradoxical growth responses of KPL-1 cells in vivo. To support this hypothesis, an antiangiogenic agent, TNP-470, was administered to mice bearing KPL-1 tumors. TNP-470 significantly inhibited the growth of KPL-1 tumors stimulated by MPA. Antiangiogenic agents may be effective for the treatment of hormone-refractory breast cancer.
Antibiotics, Antineoplastic↗
Endocrine therapies for patients with recurrent breast cancer: predictive factors for responses to first- and second-line endocrine therapies.
Breast cancer patients have been treated with four different hormonal agents, antiestrogen, progestin, luteinizing hormone-releasing hormone agonist and aromatase inhibitor, during the past 7 years in Japan. To investigate the efficacy of these agents for the treatment of recurrent breast cancer patients, we conducted a retrospective multi-institute survey in Japan. The clinico-pathological data of 131 patients, who received endocrine therapy as first-line treatment between 1993 and 1998, were collected from seven institutes. The median age of the patients was 55 (range 27-92) years, 75% of their primary tumors were estrogen receptor (ER)-positive or unknown, and 95% of the dominant metastatic sites were bone, soft tissue or lungs. The objective response rate to first-line endocrine therapy was 42.7%, and that to second-line therapy 42.5% (17 of 40 patients). Multiple regression analyses of predictive factors for a response to first- and second-line endocrine therapies indicated two independent factors, ER status of the primary tumors and dominant site of metastasis, for the former, and one independent factor, a response to first-line endocrine therapy, for the latter. Analysis of relationships between sequences of use of hormonal agents and objective response rates revealed that the choice of first-line hormonal agent did not influence the overall efficacy of first- and second-line endocrine therapies. Overall survival after first recurrence in patients with tumors exhibiting an objective response or stable disease to first-line endocrine therapy was significantly better than that in patients with tumors exhibiting progressive disease (p < 0.01). These findings suggest that an adequate selection of recurrent breast cancer patients referring the ER status, dominant site of metastasis and a prior response to endocrine therapy may contribute to better clinical outcomes of the patients.
Antineoplastic Agents, Hormonal↗
All-trans-retinoic acid modulates expression levels of thyroglobulin and cytokines in a new human poorly differentiated papillary thyroid carcinoma cell line, KTC-1.
A new human thyroid carcinoma cell line, KTC-1, was established from the malignant pleural effusion of a recurrent thyroid carcinoma patient. Cytogenetic analysis revealed a normal karyotype, and no p53 mutation in exons 5-9 was detected. This cell line is tumorigenic in athymic nude mice. Histological findings by light and electron microscopy, such as the absence of follicular structures and the existence of intranuclear cytoplasmic inclusions and psammoma bodies, indicated transplanted tumors to be a poorly differentiated papillary thyroid carcinoma. A low expression level of thyroglobulin was detected by immunocytochemistry and RT-PCR. Messenger ribonucleic acid (mRNA) expression of thyroid transcription factor-1 and PAX-8 was also detected. No mRNA expression of TSH receptors, thyroid peroxidase, or Na+/I- symporter was detected. Interleukin-6 and leukemia inhibitory factor were secreted into the medium. These findings suggest this cell line to be functionally poorly differentiated. Moreover, all-trans-retinoic acid increased the mRNA expression of thyroglobulin and decreased both the mRNA expression and secretion of interleukin-6 and leukemia inhibitory factor while significantly stimulating growth. RT-PCR analysis of retinoic acid receptors (RARs) revealed that KTC-1 cells express a moderate level of RARalpha and -gamma, but a low level of RARbeta. This cell line may be useful for studying redifferentiation therapy for thyroid carcinoma.
Animals↗
Semi-quantitative comparison of the differentiation markers and sodium iodide symporter messenger ribonucleic acids in papillary thyroid carcinomas using RT-PCR.
OBJECTIVE: To investigate the levels of expression of the sodium iodide symporter (NIS) and three differentiation markers (thyroglobulin (Tg), thyroid peroxidase (TPO) and thyrotrophin receptor (TSH-R)) in 35 patients with primary (n=31) or recurrent (n=4) papillary thyroid carcinoma, and to compare the findings with clinical data. METHODS: We performed a multiplex semi-quantitative RT-PCR to analyse the relative levels of expression of Tg, TPO and TSH-R mRNAs, and a separate semi-quantitative RT-PCR for NIS mRNA. RESULTS: Tg, TPO and TSH-R mRNAs were expressed in all the patients, whereas NIS mRNA was expressed in all but eight. Analysis of the expression of the differentiation markers in all patients showed a significant correlation among Tg, TPO and NIS. With regard to the relationship between the expression of each gene and the MACIS score, there was significant correlation only for the Tg gene (P<0.05). CONCLUSIONS: The levels of expression of NIS mRNA correlated significantly with those of Tg and TPO mRNAs, but not with those of TSH-R mRNA. The relationship with clinical stage and prognostic score, however, varied among these differentiation markers.
Adult↗
Expression levels of estrogen receptor-alpha, estrogen receptor-beta, coactivators, and corepressors in breast cancer.
Recent studies have indicated that a complex machinery of transactivation of target genes by estrogen or antiestrogen through estrogen receptor (ER) exists. However, the substantial roles of ER-beta, coactivators, and corepressors in the development and progression of breast cancer remain to be elucidated. To obtain some clue to these roles, we screened the expression levels of ER-alpha, ER-beta, coactivators (SRC-1, TIF2, AIB1, CBP, and P/CAF) and corepressors (N-CoR and SMRT) in 6 normal mammary glands, 6 intraductal carcinomas, 22 invasive ductal carcinomas, and 7 breast cancer cell lines using a multiplex reverse transcription-PCR. ER-alpha mRNA expression levels significantly correlated with ER-alpha protein levels measured by enzyme immunoassay in the breast cancer tissues and cell lines. A significant correlation of expression levels was observed between ER-alpha and TIF2, AIB1, P/CAF, and N-CoR, and between ER-beta and AIB1 and CBP in the tissue samples. A significant correlation was also observed between ER-alpha and ER-beta and between ER-beta and CBP in the cell lines. The expression levels of ER-alpha, TIF2, and CBP were significantly higher in the intraductal carcinomas than those in the normal mammary glands. In addition, the expression levels of ER-alpha and N-CoR were significantly higher in the intraductal carcinomas than those in the invasive ductal carcinomas. These findings suggest a positive correlation of expression levels among ER-alpha and cofactors and among ER-beta and cofactors, an up-regulation of expression levels of ER-alpha and cofactors during the development of intraductal carcinomas from normal mammary glands, and a decrease in their expression levels during the progression of breast cancer.
Breast↗
[Comparison of whole-body MR imaging and bone scintigraphy in the detection of bone metastases from breast cancer].
The aim of this study was to investigate the usefulness of whole body MR imaging (WB-MRI) in the detection of bone metastases from breast cancer and to compare the results with those from bone scintigraphy. In 21 patients with suspected bone metastasis from breast cancer, both bone scintigraphy and WB-MRI were performed. With WB-MRI, coronal images were obtained using a body coil in an FOV of 48 cm, and sequences of fast short TI inversion recovery (STIR) and gadolinium-enhanced fast spoiled GRASS (SPGR) were used in three parts: from the head to the thorax, the abdomen to the pelvis, and the lower extremities. Of the total 105 metastatic bone lesions, 65 (61.9%) were detected by bone scintigraphy, 98 (93.3%) by fast STIR, and 74 (70.5%) by fast SPGR. Thus, the detection of bone metastases by WB-MRI was excellent. However, detectability in the ribs was lower for WB-MRI than for bone scintigraphy. Contrast-enhanced MRI was useful in the differentiation of osteosclerotic lesions, in which high signal intensity is rare, pleural effusion, which has high signal intensity on STIR, and bone metastatic lesions. In conclusion, WB-MRI showed high reliability in the detection of bone metastatic lesions from breast cancer.
Adult↗
[A case of advanced breast cancer associated with humoral hypercalcemia that responded to medroxyprogesterone acetate and docetaxel].
A 67-year-old woman with a left advanced breast cancer was admitted to our hospital. Chest CT revealed a parasternal lymph nodal metastasis invading into the sternum, an axillary lymph nodal metastasis, and a lung metastasis. The clinical stage of the patient was i.v. (T4bN2M1). Laboratory examination showed humoral hypercalcemia. After controlling the hypercalcemia with alendronate, sodium hydrate she received chemoendocrine therapy with medroxyprogesterone acetate (MPA) (800 mg/day) and docetaxel (60 mg/body once every three weeks). A complete response was obtained in the primary and metastatic lesions after 3 cycles of docetaxel. This case suggests the efficacy of the combined therapy with MPA and docetaxel on advanced breast cancers.
Administration, Oral↗
[Estrogen and progesterone receptors in breast cancer].
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Antineoplastic Agents, Hormonal↗
[Aromatase inhibitors for treatment of advanced breast cancers].
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Anastrozole↗
Current Status and Controversial Issues concerning Endocrine Therapy for Patients with Recurrent Breast Cancer in Japan.
BACKGROUND: Four different endocrine therapeutic agents have been used in Japan since 1996. However, a consensus regarding proper use of these agents has notyet been established. Therefore, a questionaire survey of Japanese breast cancer authorities on endocrine therapy and a multi-institute survey to investigate the efficacy of a single first-line endocrine therapy for recurrent breast cancerwere conducted. MATERIALS AND PATIENTS: A total of 279 questionaires were sent to the Councilors of the Japanese Breast Cancer Society. The clinico-pathological data of 77 breast cancer patients who underwent a single first-line endocrine therapy were collected from five institutes. RESULTS: The response rate to this questionaire survey was 67.4%. The resultsshow that many authorities consider that: 1) both ER and PgR in primary tumors should be measured, 2) patient age, the disease-free interval and postoperative adjuvant therapy do not provide enough information for the selection of endocrine therapies, 3) antiestrogen and LH-RH agonists should be used as first-line endocrine therapies, 4) combined endocrine therapies, such as an antiestrogen plus an LH-RH agonist, should be used, 5) the optimal sequence of use of endocrine therapeutic agents is most controversial. The objective response rate to first-line endocrine therapies was 40.3% and the duration of response was over 15 months.The objective response rate to second-line endocrine therapies was 42.1%. A multiple regression analysis of predictive factors for the efficacy of first-line endocrine therapies indicated two factors, the disease-free interval and dominantsite of metastasis, to be significant. Conclusions: This questionaire survey suggests that clinical trials to investigate the optimal sequence of use of endocrine therapies and to clarify the usefulness of combined endocrine therapies should be conducted. Single first- or second-line endocrine therapies for recurrent breast cancer are effective and should be carried out by general clinicians.
Journal Article↗