Biomedical subjects

Takuya Moriya

Publications and source records attributed to Takuya Moriya.

At least 19 recordsLinked to original sources

PubMed2007

5Alpha-reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production.

Previous in vitro studies demonstrated that bioactive androgen 5alpha-dihydrotestosterone (DHT) exerted antiproliferative effects through an interaction with androgen receptor (AR) in breast carcinoma cells. However, AR status has not been examined in association with DHT concentration in breast carcinoma tissues, and significance of androgenic actions remains unclear in breast carcinomas. Therefore, in our study, we first examined intratumoral DHT concentrations in 38 breast carcinoma tissues using liquid chromatography/electrospray tandem mass spectrometry. Intratumoral DHT concentration was positively associated with 5alpha-reductase type 1 (5alphaRed1), and negatively correlated with aromatase. We then examined clinical significance of AR and 5alphaRed1 status in 115 breast carcinoma tissues by immunohistochemistry. Breast carcinomas positive for both AR and 5alphaRed1 were inversely associated with tumor size or Ki-67. These patients showed significant associations with a decreased risk of recurrence and improved prognosis for overall survival, and the AR / 5alphaRed1 status was demonstrated an independent prognostic factor. Moreover, we examined possible regulation of DHT production by aromatase in in vitro studies. DHT synthesis from androstenedione in MCF-7 cells was significantly inhibited by coculture with aromatase-positive stromal cells, which was significantly reversed by addition of aromatase inhibitor exemestane. These results suggest that intratumoral DHT concentration is mainly determined by 5alphaRed1 and aromatase in breast carcinoma tissues, and antiproliferative effect of DHT may primarily occur in the cases positive for both AR and 5alphaRed1. Aromatase inhibitors may be more effective in these patients, possibly due to increasing local DHT concentration with estrogen deprivation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2006

Oncolytic viral therapy by bladder instillation using an E1A, E1B double-restricted adenovirus in an orthotopic bladder cancer model.

OBJECTIVES: To investigate the therapeutic effect of AxdAdB-3, a double-restricted oncolytic adenovirus harboring a mutant E1A and an E1B-55KD deletion, on human bladder cancer cell lines and the SCID mouse model of orthotopic bladder cancer. METHODS: The cytopathic effects of AxdAdB-3 were evaluated in several cell lines (YTS-1, YTS-3, T24, J82, 5637) derived from human bladder or ureteral cancer and in a normal bladder mucosa-derived cell line (HCV29) with AxCAlacZ (control) or AxE1AdB (E1B-55KD-defective adenovirus) or dl922-947 (E1A-mutated adenovirus). The efficacy of bladder instillation therapy with AxdAdB-3 for orthotopic bladder cancer of SCID mice was investigated. The oncolytic effects were monitored by ultrasound examination. RESULTS: AxdAdB-3 caused the oncolysis of bladder cancer cell lines in vitro, and it was more cytopathic than AxE1AdB or dl922-947 in the cancer cell lines. AxdAdB-3 was not cytotoxic against HCV29. Direct instillation of AxdAdB-3 into the bladder of the orthotopic model inhibited tumor growth, leading to significantly prolonged survival. CONCLUSIONS: Oncolytic viral therapy delivered by instillation of AxdAdB-3 is a promising tool for treating bladder cancer.

Adenoviridae↗

PubMed2006

Steroid sulfatase and estrogen sulfotransferase in human prostate cancer.

BACKGROUND: Estrogen sulfotransferase (EST) and steroid sulfatase (STS) are known to be involved in in situ estrogen production in estrogen dependent human cancer such as breast cancer, but unknown in prostate cancer. MATERIALS AND METHODS: We first examined whether these enzymes above were expressed and actually involved in estrogen production and metabolism in prostate cancer cell lines (LNCaP, DU-145, and PC-3). We than examined the expression of EST and STS in human prostate cancer tissues obtained from surgery (n = 52) using immunohistochemistry. RESULTS: mRNAs of both enzymes were detected in all prostate cancer cell lines examined, and the synthesis of estrone (E(1)) and estradiol (E(2)) was also confirmed in these cell lines. In addition, STS immunoreactivity was detected in 44 cases (85%) and EST in 39 cases (75%), respectively. CONCLUSIONS: STS and EST are expressed and may be involved in local production and metabolism of estrogens in human prostate cancers.

Cell Line, Tumor↗

PubMed2006

Vasohibin prevents arterial neointimal formation through angiogenesis inhibition.

Vasohibin is a VEGF-inducible angiogenesis inhibitor in vascular endothelium. Here we examined the presence of vasohibin in human arterial wall, and found it in endothelium of adventitial microvessels in atherosclerotic lesion. Adventitial angiogenesis is involved in the progression of neointimal formation. Even in the presence of endogenous angiogenesis inhibitors, pathological angiogenesis persists. However, the supplementation of exogenous angiogenesis inhibitors can prevent pathological angiogenesis. We evaluated the potential role of vasohibin in neointimal formation. Adenovirus-mediated human vasohibin gene transfer in mouse liver resulted in the release of vasohibin in plasma and exhibited anti-angiogenic effects at remote sites. This gene transfer inhibited adventitial angiogenesis, macrophage infiltration, and neointimal formation after cuff placement on mouse femoral artery. Vasohibin exhibited no direct effect on migration and proliferation of smooth muscle cells. Thus, vasohibin has an activity to prevent neointimal formation by inhibiting adventitial angiogenesis.

Adult↗

PubMed2006

Cellular features of endometrial hyperplasia and well differentiated adenocarcinoma using the Endocyte sampler: Diagnostic criteria based on the cytoarchitecture of tissue fragments.

BACKGROUND: Because cellular atypia is often limited in endometrial hyperplasia and well-differentiated endometrial adenocarcinoma (WHO Grade 1 adenocarcinoma), diagnostic criteria for endometrial cytology have not been fully established. New diagnostic criteria based on the composition and architecture of tissue fragments (cytoarchitecture) in the smears were used in the present study. Cytologic features are of less importance because the distinction between endometrial hyperplasia and Grade 1 adenocarcinoma relies more on architectural features than cellular changes. Cell clumps of various size are usually collected abundantly with cytologic material using a disposable scraping device and it was noticed that those cell clumps reflected the histologic architecture. The purpose of the current study was to determine the form of the cytoarchitecture that reflects the histologic structure and to examine the cellular features in endometrial hyperplasia and Grade 1 adenocarcinoma. METHODS: The frequency of each type of cell clump (tube or sheet-shaped pattern, dilated or branched pattern, irregular protrusion, and papillotubular pattern) were obtained from 49 cases of normal proliferative endometrium (NPE) (patient age range, 28-51 yrs; average age, 39.9 yrs), 63 cases of endometrial hyperplasia without atypia (EH) (patient age range, 35-65 yrs; average age, 47.7 yrs), 13 cases of endometrial hyperplasia with atypia (AEH) (patient age range 47-65 yrs; average age, 53.8 yrs), and 49 cases of Grade 1 adenocarcinoma (patient age range, 42-73 yrs; average age, 58.9 yrs). RESULTS: Certain characteristics of the cytoarchitecture were observed. In the NPE, cell clumps with a tube or sheet-shaped pattern were found in 97.5% of cases. In the EH, cell clumps with a dilated or branched pattern were found in 34.9% of cases. In the Grade 1 adenocarcinoma, cell clumps with irregular protrusions were found in 61.8% cases, whereas a papillotubular pattern was present in 29.7% of cases. CONCLUSIONS: The results of the current study revealed that cytoarchitectural criteria appear to be more useful for the cytologic assessment of endometrial lesions, especially for the diagnosis of endometrial hyperplasia and Grade 1 adenocarcinoma.

Adenocarcinoma↗

PubMed2006

Isolation and characterization of vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin.

OBJECTIVE: We recently isolated vasohibin, a novel vascular endothelial growth factor (VEGF)-inducible endothelium-derived angiogenesis inhibitor. Our aim is to find DNA sequences homologous to vasohibin and determine their expression profile. METHODS AND RESULTS: By the search of DNA sequences in the database, we found one homologous gene and designated it vasohibin-2. Overall amino acid sequence homology between the prototype vasohibin (vasohibin-1) and vasohibin-2 was >50%. Vasohibin-2 exhibited antiangiogenic activity. Vasohibin-2 expression in cultured endothelial cells was low and not inducible by the stimulation that induced vasohibin-1. However, the immunohistochemical analysis revealed that vasohibin-1 and -2 were diffusely expressed in endothelial cells in embryonic organs during mid-gestation. After that time point, vasohibin-1 and -2 became faint, but persisted to a certain extent in arterial endothelial cells from late gestation to neonate. Expression of vasohibin-1 and -2 could be augmented in vivo by local transfection with the VEGF gene in the embryonic brain or by cutaneous wounding in adult mice. CONCLUSIONS: These results suggest that vasohibin-2, in combination with vasohibin-1, forms a novel family of angiogenesis inhibitors.

Angiogenesis Inhibitors↗

PubMed2006

Immunolocalization of liver receptor homologue-1 (LRH-1) in human breast carcinoma: possible regulator of insitu steroidogenesis.

Liver receptor homologue-1 (LRH-1) belongs to a class of nuclear orphan receptor. We examined immunolocalization of LRH-1 in 106 breast carcinomas. LRH-1 immunoreactivity was detected in 43% of the invasive ductal carcinoma. It was negatively correlated with clinical stage, histological grade and HER2 status, and positively associated with sex-steroid receptors, steroidogenic acute regulatory protein, P450 side-chain cleavage, and 3beta-hydroxysteroid dehydrogenase. LRH-1 immunoreactivity was also detected in 28% of the ductal carcinoma in situ. These results suggest that LRH-1 is frequently detected in breast carcinoma tissues, and plays important roles including the regulation of in situ steroidogenesis.

Breast Neoplasms↗

PubMed2006

Expression of the steroid and xenobiotic receptor and its possible target gene, organic anion transporting polypeptide-A, in human breast carcinoma.

Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) has been shown to play an important role in the regulation of genes related to xenobiotic detoxification, such as cytochrome P450 3A4 and multidrug resistance gene 1. Cytochrome P450 enzymes, conjugation enzymes, and transporters are all considered to be involved in the resistance of breast carcinoma to chemotherapeutic or endocrine agents. However, the expression of SXR/hPXR proteins and that of its target genes and their biological or clinical significance have not been examined in human breast carcinomas. Therefore, we first examined SXR/hPXR expression in 60 breast carcinomas using immunohistochemistry and quantitative reverse transcription-PCR. We then searched for possible SXR/hPXR target genes using microarray analysis of carcinoma cells captured by laser microscissors. SXR/hPXR was detected in carcinoma tissues but not in nonneoplastic and stromal cells of breast tumors. A significant positive correlation was detected between the SXR/hPXR labeling index and both the histologic grade and the lymph node status of the carcinoma cases. Furthermore, in estrogen receptor-positive cases, SXR/hPXR expression was also positively correlated with expression of the cell proliferation marker, Ki-67. Microarray analysis showed that organic anion transporting polypeptide-A (OATP-A) was most closely correlated with SXR/hPXR gene expression, and both OATP-A mRNA and protein were significantly associated with SXR/hPXR in both breast carcinoma tissues and its cell lines. These results suggest that SXR/hPXR and its target gene, such as OATP-A, may play important roles in the biology of human breast cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Endometrial glandular and stromal breakdown, part 2: cytomorphology of papillary metaplastic changes.

Careful cytomorphologic evaluation of abnormal endometrial lesions has made accurate and reproducible microscopic assessment possible. Histopathology of patients with dysfunctional uterine bleeding due to an anovulatory cycle usually contain endometrial glandular and stromal breakdown (EGBD) and papillary metaplasia on the endometrial surface epithelium, if an appropriate sample has been collected. We often recognized abnormal cell clumps in the cytological smears with EGBD cases. They were composed of metaplastic cells, and some irregular small projection figures were observed from the margins of the cell clumps. We describe the quantitation of metaplastic clumps with irregular protrusions (MCIP) in endometrial endocyte samples. The current study presents the cytomorphological characteristics of the metaplastic changes recognized in EGBD cases. During a 7-yr period, 144 cases for which histopathological diagnoses were obtained following endometrial curettage, after collecting a direct endometrial sample using the endocyte. The material comprised 49 cases of normal proliferative endometrium (NPE) (patients aged 28-51, average 39.9), 32 cases of EGBD (patients aged 30-67, average 49.6), and 63 cases of endometrial hyperplasia without atypia (EH) (patients aged 35-65, average 47.7). The following points were investigated: (1) the occurrence of metaplastic cells; (2) the occurrence and the frequency of MCIP; and (3) the occurrence of MCIP that contains condensed stromal clusters. Metaplastic cells were seen in 93.8% of the EGBD cases. Cytomorphologic pattern identified with MCIP was 90.6%, and its frequency showed 16.1%. The occurrence of MCIP that contain condensed stromal clusters (93.1%) showed a strong association in comparison with other lesions, such as NPE and EH. Our data appear to indicate that the appearance of MCIP with condensed stromal clusters originated from the papillary metaplasia, which occurred on the endometrial surface epithelium. The cytologic observation of those cells may be a useful indicator for providing the nature of EGBD endometrium.

Adult↗

PubMed2006

Endometrial glandular and stromal breakdown, part 1: cytomorphological appearance.

Endometrial carcinoma is the most common invasive neoplasm of the female reproductive tract. Early detection and accurate diagnosis of these lesions and its precursor by endometrial cytology is now accepted in Japan and regarded as an effective primary method of evaluating endometrial pathology (atypical hyperplasia or carcinoma). Careful cytomorphologic evaluation of the abnormal endometrial lesions has made possible an accurate and reproducible microscopic assessment. The current study was conducted to determine the significance of endometrial cytology on disordered endometrium associated with anovulation when compared with endometrial hyperplasia. From January 1998 through April 2004, 144 cases on which histopathological diagnoses were obtained by endometrial curettage after taken direct endometrial sample by Endocyte. The materials comprise 49 cases of normal proliferative endometrium, and 63 cases of endometrial hyperplasia without atypia were prepared as control cases. The cytomorphology was examined involving so-called endometrial glandular and stromal breakdown (EGBD). EGBD cases evidenced significant numbers of stromal cells condensed and formed compact nests with hyperchromatic nuclei and little or no cytoplasm. They were often associated with fragmented clusters of endometrial glands with condensed cluster of stromal cells. Both the fragmented cluster of endometrial glands and condensed cluster of stromal cells are a characteristic cytologic feature of EGBD endometrium on the cyto-architectural diagnosis. The combination of these cellular patterns is highly specific to this abnormal pathological condition in EGBD endometrium. To improve the accuracy of the cytodiagnosis, it is important that the cytology of the EGBD endometrium should be diagnosed negative; as a result, we can achieve successful endometrial cytology with cyto-architectural criteria for the endometrial pathology.

Adult↗

PubMed2006

New trends of immunohistochemistry for making differential diagnosis of breast lesions.

Immunohistochemistry is widely used for pathological diagnosis of breast lesions. Other than hormone receptors and HER2/neu analysis for primary breast carcinomas, several markers may be useful for differential diagnoses, although in limited situations. To decide the malignant potential of intraductal proliferative lesions, analysis for the staining pattern of cytokeratins may be a good reference. Most ductal carcinoma in situ cases are diffusely positive for luminal cell markers (CK8, CK18, CK19), but negative for basal cell markers (CK5/6 and CK14). However, usual ductal hyperplasia may show the mosaic staining patterns for any of these markers, which may indicate a heterogeneous cell population in benign lesions. Myoepithelial markers (alpha-SMA, myosin, calponin, p63, CD10) are almost consistently positive for benign papillomas but they do not completely distinguish intraductal papillary carcinomas. Preservation of myoepithelial layer is the diagnostic key when looking at benign sclerosing lesions, including carcinoma with pseudoinvasive structures. E-cadherin is mostly positive for ductal carcinomas but negative for lobular carcinomas. Some of the lobular carcinomas are positive for 34betaE12, but they are consistently negative for CK5/6. Comparison with histopathological findings of hematoxylin and eosin is essential to make proper diagnosis in the individual case.

Biomarkers, Tumor↗

PubMed2006

Recombinant AAV-transduced iris pigment epithelial cell transplantation may transfer vector to native RPE but suppress systemic dissemination.

PURPOSE: To determine whether adenoassociated virus (AAV) vectors transduced into iris pigment epithelial (IPE) cells and transplanted into the subretinal space of rats will transfer the AAV genome to the host cells and whether the vectors are disseminated systemically. METHODS: Recombinant (r)AAV was transduced into rat IPE cells and transplanted into the subretinal space of rats. For the control, rAAVs alone were injected subretinally. The transplanted IPE cells were detected by LacZ staining. Immunohistochemistry, electron microscopy, electroretinography, and fluorescein-dextran angiography were performed. DNA was extracted from various organs and blood and examined for the AAV genome by polymerase chain reaction. RESULTS: No toxicity from rAAV transduction was observed in vitro. LacZ was expressed in the transplanted cells 1 and 2 weeks after transplantation. At 4 and 12 weeks, fewer transplanted cells were detected than at 1 week, and LacZ expression was occasionally detected at the level of host retinal pigment epithelial (RPE) cells. Expression was also detected in ciliary body epithelial cells. The electroretinograms and fluorescein-dextran angiography were only mildly altered. Significantly lower levels of AAV genome were detected in the organs and blood of rats receiving rAAV-IPE cell transplants than with direct intravenous injection of AAV vectors. CONCLUSIONS: AAV-mediated LacZ was expressed in the transplanted cells after subretinal transplantation, and the transplanted IPE cells may transfer the rAAV to host tissues, such as RPE cells, long after the transplantation. This method of gene delivery did not lead to systemic dissemination of the vectors.

Animals↗

PubMed2006

Osteosarcoma in a patient with neurofibromatosis type 1: a case report and review of the literature.

Neurofibromatosis type 1 (NF1) or von Recklinghausen's disease is a genetic disease generally characterized by café-au-lait spots and neurofibromas. Malignant tumors of the nervous system, such as malignant schwannomas, gliomas, or astrocytomas, have been well known to coexist with neurofibromatosis. However, occurrence of malignant tumors unrelated to the nervous system is rare. We report an unusual case of a 29-year-old NF1 female suffering from malignant peripheral nerve sheath tumor (MPNST) that eventually developed osteosarcoma in the proximal femur. Osteosarcoma is the most common high-grade malignant bone tumor in which the neoplastic cells produce osteoid. At 23 and 24 years old, she underwent excision of MPNST in the left posterior thigh. No osteosarcomatous portion was identified in these specimens. The patient underwent postoperative chemotherapy. At 29, left proximal thigh pain and swelling appeared. Computed tomography demonstrated cortical bone destruction in the left proximal femur where MPNST occurred. Magnetic resonance imaging revealed extraskeletal growth of the tumor. Bone scintigraphy demonstrated increased uptake in the left proximal femur. Hip disarticulation was performed. The removed tumor was composed of highly anaplastic cells. Lace-like irregular osteoid formation was observed among the tumor cells. MPNST component was totally absent. The tumor was diagnosed as osteoblastic type osteosarcoma. Two months after disarticulation the patient died of bilateral pulmonary metastasis. The correlation between the histogenesis of osteosarcoma and the genetic abnormality in NF1 patients has not been elucidated, but the finding of osteosarcomatous transformation in this case suggests the divergent cellular differentiation to mesenchymal malignant tumors of neuroectodermal tissue in NF1 patients.

Adult↗

PubMed2006

Serum antibody against granulocyte/macrophage colony-stimulating factor and KL-6 in idiopathic pulmonary alveolar proteinosis.

Here we describe a case of idiopathic pulmonary alveolar proteinosis (I-PAP), in which anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) antibody and high level of KL-6 were found in the serum. Anti-GM-CSF antibody is responsible for I-PAP, and KL-6 is a serum marker for the activity of diffuse interstitial lung disease. A 38-year-old woman, who had no symptoms, was found to have an abnormal shadow on chest radiograph 5 years previously at a health check up. Chest radiograph showed a patchy shadow in the left lower lung field. Thoracoscopic biopsy was performed because the shadow had gradually expanded during the 5 years. Histological examination revealed proteinous material filling the alveoli and positive staining by the PAS method, suggesting PAP. Anti-GM-CSF antibody and a high level of KL-6 were detected in the serum at the time of diagnosis. Three years later, the shadow disappeared spontaneously. During this period, the level of KL-6 dramatically decreased, although that of GM-CSF antibody remained unchanged. The present case suggests that the serum level of the anti-GM-CSF antibody represents a useful marker for the diagnosis but not for follow-up of the clinical course. On the contrary, KL-6 is an excellent marker for the assessment of the clinical course of I-PAP.

Adult↗

PubMed2006

Comparison of MDCT and MRI for evaluating the intraductal component of breast cancer.

OBJECTIVE: The purpose of our study was to compare the accuracy of MDCT and MRI for evaluating the intraductal component of breast cancer. MATERIALS AND METHODS: Sixty-nine patients with histologically proven invasive carcinoma underwent MDCT and MRI. Retrospectively, two radiologists performed a blinded review of the MDCT and MRI. Cases with intraductal component enhancement were classified into two morphologic types: ductal extension and segmental distribution. The lengths of the main tumor and of the intraductal component were measured in cases with ductal extension. For cases with segmental distribution, only the maximum length of the tumor was measured. RESULTS: The sensitivity, specificity, and accuracy in detecting the intraductal component were 61%, 88%, and 71%, respectively, using MDCT; and 75%, 88%, and 80%, respectively, using MRI. MRI revealed the presence of the intraductal component with significantly higher sensitivity than did MDCT (p = 0.031). In the analysis of the length of the intraductal component in cases with ductal extension, which had relatively small intraductal components, underestimation by 15 mm or more was significantly less frequent with MRI than with MDCT (p = 0.008). There was no significant difference between MDCT and MRI in the evaluation of the maximum length of tumors in cases with segmental distribution, which had relatively large intraductal components. CONCLUSION: Compared with MDCT, MRI revealed the presence of the intraductal component with higher sensitivity and equivalent specificity. In cases with ductal extension, MRI is more precise than MDCT for determination of the margin for surgical removal, with less underestimation of the extent of the intraductal component.

Adult↗

PubMed2006

[A case of advanced colon cancer with metastases to both para-aortic lymph nodes and cervical vertebrae effectively treated by TS-1 therapy].

The patient was a 68-year-old woman who had cecal cancer with para-aortic lymph node metastases. Ileocecal resection was performed palliatively. Since metastasis to cervical vertebrae was detected after the operation, she received radiation therapy of 14 Gy to improve neck pain. Chemotherapy with TS-1 (80 mg/day) was started on an outpatient basis (4 weeks administration followed by a 2-week drug-free period). After 4 courses of this chemotherapy, metastases to both para-aortic lymph nodes and cervical vertebrae were remarkably reduced on CT and PET. Throughout the period of treatment, there was no adverse effect and this treatment has been maintained. In conclusion, this case seems significant from the viewpoint of achieving a partial response to TS-1 and maintaining a high quality of life. Moreover,we identified the presence of TS and DPD using an immunohistochemical staining technique. The primary tumor was positive for DPD stain test and negative for TS stain test. It was suggested that this cancer especially would respond to TS-1 chemotherapy.

Adenocarcinoma↗

PubMed2006

New development in intracrinology of breast carcinoma.

Intratumoral metabolism and synthesis of estrogens as a result of the interactions of various enzymes are considered to play very important roles in the pathogenesis and development of hormone dependent breast carcinoma. Among these enzymes, intratumoral aromatase plays as important role converting serum androgens to estrogens in situ, and serves as a source of estrogen, especially in postmenopausal patients with breast carcinoma. However, other enzymes such as the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes, estrogen sulfatase (STS) and estrogen sulfotransferase, also play pivotal roles in intratumoral estrogen production. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone (E1), and thereby serve to modulate the tissue levels of bioactive E2 in human breast carcinoma. 17Beta-HSD type 1 catalyzes primarily the reduction of estrone (E1) to estradiol (E2), whereas 17beta-HSD type 2 catalyzes primarily the oxidation of E2 to E1. In human breast disease, 17beta-HSD type 1 is expressed in proliferative disease without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17Beta-HSD type 2 has not been detected in any of these breast lesions. In addition, 17beta-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E1, produced as a result of in situ aromatization, to E2, a biologically potent estrogen, which exerts estrogenic actions on tumor cells through estrogen receptor, especially the alpha subtype in carcinoma cells. Therefore, inhibiting intratumoral 17beta-HSD type 1 is also considered to contribute to inhibition of cell proliferation by decreasing intratumoral estradiol. Estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to inactive estrogen sulfates, while steroid sulfatase (STS) hydrolyzes estrone sulfate (E1-S) to estrone. EST immunoreactivity was recently demonstrated to be significantly associated with a decreased risk of recurrence or improved prognosis by both uni- and multivariate analyses. STS immunoreactivity was significantly associated with an increased risk of recurrence by univariate analysis. These findings also suggest that EST and STS plays important roles in regulation of in situ estrogen production, and EST especially is a potent prognostic factor in human breast carcinoma. Therefore, the inhibition of intratumoral STS might also serve as an endocrine therapy in postmenopausal patients. It is also important to note that the status of intratumoral aromatase, 17beta-HSD type 1, EST and STS in human breast cancer tissues is variable and not necessarily correlated with each other, which suggests different potential sources of intratumoral estrogens among individual patients with breast cancer. These findings indicate that there are patients who could benefit more from inhibition of these intratumoral enzymes rather than aromatase inhibition as an endocrine therapy. Therefore, it will become very important to examine the intratumoral levels of 17beta-HSD type 1 and STS in the resected specimens of human breast carcinoma as potential targets of novel endocrine therapy in the near future.

17-Hydroxysteroid Dehydrogenases↗

PubMed2006

Immunohistochemical evaluation for hormone receptors in breast cancer: a practically useful evaluation system and handling protocol.

This article reviews the current status of hormone receptor evaluation in and out of Japan, and introduces the proposed working protocol of the task force for Adequate immunohistochemical evaluation in routine practice for breast cancer by the Japanese Breast Cancer Society. Understanding the principles and the developmental process of immunohistochemistry helps us to utilize a scoring system adequately. Methodologies of hormone receptor examination and immunohistochemical procedures are briefly introduced. Each scoring system is based on different principles. The proposed working protocol takes into account the reproducibility of results among observers, institutions and staining procedures, which is justified based on the current situation in Japan. Future directions for the standardization of immunohistochemical hormone receptor evaluation are also described.

Breast Neoplasms↗