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Yasuhiro Tamaki

Publications and source records attributed to Yasuhiro Tamaki.

At least 19 recordsLinked to original sources

Connexin26 expression is associated with lymphatic vessel invasion and poor prognosis in human breast cancer.

PURPOSE: Cx26, which is a constituent of the connexin family, has recently been shown to promote metastasis through enhancing the vascular invasion in mouse melanoma cells. In this study, we have investigated whether or not Cx26 expression is associated with vascular invasion and recurrences in human breast cancers. EXPERIMENTAL DESIGN: Cx26 expression was studied in 152 invasive breast cancers by immunohistochemistry. In order to investigate the blood vessel invasion and lymphatic vessel invasion with precision, immunohistochemical staining of blood vessels and lymphatic vessels was carried out using anti-CD34 and anti-D2-40 antibodies, respectively. RESULTS: Cx26 was positive in 51.3% (78/152) of the breast tumors. A statistically significant association was observed between Cx26 expression and large tumor size (P = 0.013) or high histological grade (P = 0.043). Frequency of blood vessel invasion was higher in Cx26-positive tumors (5.1%, 4/78) than in Cx26-negative tumors (1.4%, 1/74) though not statistically significant (P = 0.210). Lymphatic vessel invasion was significantly (P = 0.001) more frequent in Cx26-positive tumors (39.7%) than in Cx26-negative tumors (14.9%). Patients with Cx26-positive tumors showed a significantly (P < 0.001) poorer prognosis than those with Cx26-negative tumors. Multivariate analysis showed that Cx26 (P < 0.05) expression was an independent prognostic factor. CONCLUSIONS: Cx26 expression is associated with lymphatic vessel invasion, large tumor size, high histological grade, and poor prognosis in human breast cancers. Cx26 seems to enhance the metastasis probably through promoting the lymphatic vessel invasion. Cx26 might be clinically useful as a new prognostic factor.

Antibodies, Monoclonal↗

Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women.

PURPOSE: Somatic mutations of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase, have recently been shown to play an important role in the pathogenesis and progression of human breast cancers. In this study, the frequency of PIK3CA mutations and their relationship with clinicopathologic and biological variables were investigated in Japanese breast cancers. EXPERIMENTAL DESIGN: Mutational analysis of PIK3CA was done in 188 primary breast cancers of Japanese women. Relationship of these mutations with various clinicopathologic variables [histologic type, tumor size, histologic grade, lymph node status, estrogen receptor (ER)-alpha and progesterone receptor status, and prognosis], biological variables [phospho-AKT (pAKT) and HER2 expression determined by immunohistochemistry], and p53 mutation status was studied. RESULTS: Missense mutations of PIK3CA were found in 44 of 158 invasive ductal carcinomas, 4 of 10 invasive lobular carcinomas, 1 of 4 mucinous carcinomas, 2 of 2 squamous carcinomas, and 2 of 2 apocrine carcinomas, but no mutation was found in 12 noninvasive ductal carcinomas. PIK3CA-mutated tumors were found to be more likely to be ER-alpha positive (P < 0.05) and pAKT positive (P < 0.05). There was no significant association between PIK3CA mutations and p53 mutation status. PIK3CA mutations were significantly (P < 0.05) associated with a favorable prognosis, and multivariate analysis showed that PIK3CA mutation status was a significant (P < 0.05) prognostic factor independent of the other conventional prognostic factors. CONCLUSIONS: The frequency of PIK3CA mutations in Japanese breast cancers is similar to that of Caucasian breast cancers. Association of PIK3CA mutations with positive pAKT and positive ER-alpha suggests that PIK3CA mutations might exert their effects through activation of the phosphatidylinositol 3-kinase/AKT/ER-alpha pathway. PIK3CA mutations seem to have a potential to be used as an indicator of favorable prognosis.

Breast Neoplasms↗

Demonstration of adiponectin receptors 1 and 2 mRNA expression in human breast cancer cells.

Recently, we have shown that low adiponectin levels are significantly associated with an increased breast cancer risk. It seems to be very important to study the expression of adiponectin receptor 1 (AdipoR1) and receptor 2 (AdipoR2) in the human breast epithelial cells and breast cancer cells in order to clarify whether or not adiponectin exerts its effects directly on these cells. Expression of adiponectin, AdipoR1, and AdipoR2 mRNA was determined by RT-PCR assay using the RNA samples obtained from human breast cancer cell lines (MCF-7, T47D, SKBR3, and MDA-MB231), HMEC (primary culture of normal human mammary epithelial cells), adipose tissues (axilla) as well as breast cancer cells and normal breast epithelial cells selectively collected from breast cancer tissues by laser microdissection (LMD). Adiponectin mRNA expression was observed only in the adipose tissues. On the other hand, AdipoR1 and AdipoR2 mRNA expression was observed in all four breast cancer cell lines, HMEC, adipose tissues as well as breast cancer cells and normal breast epithelial cells selectively collected by LMD. In addition, AdipoR1 and AdipoR2 expression in both normal breast epithelial cells and breast cancer cells was confirmed by immunohistochemistry. These results suggest a possibility that adiponectin might modulate the growth of normal breast epithelial cells and breast cancer cells directly through AdipoR1 and AdipoR2 receptors, and that the association of low serum adiponectin levels with a high breast cancer risk might be explained, at least in part, by the direct effect of adiponectin on the breast epithelial cells.

Adiponectin↗

A multi-class predictor based on a probabilistic model: application to gene expression profiling-based diagnosis of thyroid tumors.

BACKGROUND: Although microscopic diagnosis has been playing the decisive role in cancer diagnostics, there have been cases in which it does not satisfy the clinical need. Differential diagnosis of malignant and benign thyroid tissues is one such case, and supplementary diagnosis such as that by gene expression profile is expected. RESULTS: With four thyroid tissue types, i.e., papillary carcinoma, follicular carcinoma, follicular adenoma, and normal thyroid, we performed gene expression profiling with adaptor-tagged competitive PCR, a high-throughput RT-PCR technique. For differential diagnosis, we applied a novel multi-class predictor, introducing probabilistic outputs. Multi-class predictors were constructed using various combinations of binary classifiers. The learning set included 119 samples, and the predictors were evaluated by strict leave-one-out cross validation. Trials included classical combinations, i.e., one-to-one, one-to-the-rest, but the predictor using more combination exhibited the better prediction accuracy. This characteristic was consistent with other gene expression data sets. The performance of the selected predictor was then tested with an independent set consisting of 49 samples. The resulting test prediction accuracy was 85.7%. CONCLUSION: Molecular diagnosis of thyroid tissues is feasible by gene expression profiling, and the current level is promising towards the automatic diagnostic tool to complement the present medical procedures. A multi-class predictor with an exhaustive combination of binary classifiers could achieve a higher prediction accuracy than those with classical combinations and other predictors such as multi-class SVM. The probabilistic outputs of the predictor offer more detailed information for each sample, which enables visualization of each sample in low-dimensional classification spaces. These new concepts should help to improve the multi-class classification including that of cancer tissues.

Algorithms↗

Association of GSTP1 CpG islands hypermethylation with poor prognosis in human breast cancers.

Glutathione S-transferase P1 (GSTP1) belongs to a family of phase II metabolic enzymes that can detoxify the carcinogens and cytotoxic drugs by conjugating them with glutathione. Relationship of GSTP1 CpG islands hypermethylation or GSTP1 protein expression with clinicopathological characteristics of breast cancers was studied. The CpG islands hypermethylation status of GSTP1 gene was studied by methylation specific primer assay and GSTP1 expression was studied by immunohistochemistry in primary breast cancers. Of 174 breast tumors, 24 (14%) were found to have GSTP1 CpG islands hypermethylation. A significant association was found between GSTP1 CpG islands hypermethylation and large tumor size (P < 0.01) or lymph node metastases (P < 0.05). Relapse-free survival (RFS) rates of patients with GSTP1 CpG islands hypermethylation were significantly poorer than those without it (5-year RFS rates; 60 vs. 86%, P < 0.01). Multivariate analysis showed that GSTP1 CpG islands hypermethylation status was a statistically significant prognostic factor being independent of other conventional prognostic factors. Immunohistochemical study showed that here was a significant association between GSTP1 CpG islands hypermethylation and loss of GSTP1 expression (P < 0.01) but that RFS rates of patients with GSTP1 positive tumors were not significantly different from those with GSTP1 negative tumors. GSTP1 CpG islands hypermethylation, but not GSTP1 protein expression, is associated with a poor prognosis of breast cancers, suggesting that GSTP1 CpG islands hypermethylation has a potential to serve as a clinically useful prognostic factor.

Breast Neoplasms↗

Quantitative analysis of aromatase mRNA expression derived from various promoters (I.4, I.3, PII and I.7) and its association with expression of TNF-alpha, IL-6 and COX-2 mRNAs in human breast cancer.

The purpose of the present study was to study the aromatase mRNA expression as well as promoter usage (I.4, I.3, PII and I.7) in axillary adipose tissue (AA), mammary adipose tissue (MA), breast tumor tissue (BT) and adjacent normal breast tissue (NB), and to study the relationship between aromatase mRNA expression and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cyclooxygenase (COX)-2 mRNA expression. BT (n=108), NB (n=54), AA (n=41) and MA (n=34) from patients with breast cancer were subjected to real-time PCR assays for the mRNA levels of aromatase, TNF-alpha, IL-6 and COX-2. We also studied the usage of promoters I.4, I.3, PII and the recently reported endothelial promoter I.7. Total aromatase mRNA levels were significantly up-regulated in BT as compared with NB, AA and MA. Proportion of promoter l.4-specific transcripts against the total transcripts was significantly decreased and that of promoter l.3- and l.7-specific transcripts was significantly increased in BT than NB, AA and MA. However, the amount of transcripts from all the 4 promoters was significantly up-regulated in BT than NB, AA and MA. Estrogen receptor-alpha (ER-alpha) positive tumors showed a higher percentage of promoter I.7 usage than ER-alpha negative tumors with a marginal significance (p=0.05), and tumor with high microvessel counts tended (p=0.06) to show a higher percentage of promoter I.7 usage than those with low microvessel counts. There was a significant association between aromatase mRNA levels and TNF-alpha, IL-6 or COX-2 mRNA levels in BT, AA and MA but not in NB. These results suggest that enhanced transcription of promoters l.4, I.3, PII and I.7 explains the up-regulation of aromatase mRNA levels in BT. It has also been suggested that angiogenesis might stimulate the growth of ER-alpha positive tumors through the enhanced transcription of aromatase from promoter I.7 in endothelial cells in BT, and that TNF-alpha, IL-6 and COX-2 might be implicated in the up-regulation of aromatase mRNA in BT, AA and MA but not in NB.

Adipose Tissue↗

Quantitative analysis of aromatase, sulfatase and 17beta-HSD(1) mRNA expression in soft tissue metastases of breast cancer.

Expression of the estrogen-synthesizing genes aromatase, steroid sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type1 (17beta-HSD(1)) has been shown to be up-regulated in primary breast cancer tissue but their expression status in metastatic tumor tissue has yet to be determined. The mRNA expression levels of the three estrogen-synthesizing genes as well as of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cyclooxygenase (COX)-2, all of which have been reported to up-regulate the estrogen-synthesizing genes, were determined by means of a real-time PCR assay in 100 primary breast cancer tissues and 15 soft tissue metastases. In addition, PCR-gel electrophoresis was used to determine the proportion (%) of promoter (l.4, l.3, Pll and l.7) usage of aromatase. Aromatase and STS mRNA levels were significantly (P=0.04 and P=0.03, respectively) higher in soft tissue metastases than in primary tumors, while 17beta-HSD(1) mRNA levels tended (P=0.09) to be higher. The proportions of the promoter usages were very similar for primary tumors and soft tissue metastases, and the mRNA levels of TNF-alpha, IL-6 and COX-2 were not significantly different. Levels of aromatase, STS and 17beta-HSD(1) mRNA are up-regulated in soft tissue metastases compared to those in primary tumors, suggesting that intra-tumoral estrogen synthesis may play a significant role in the growth stimulation of tumor cells in soft tissue metastases as in primary tumors. TNF-alpha, IL-6 and COX-2, on the other hand, are unlikely to be implicated in this up-regulation.

17-Hydroxysteroid Dehydrogenases↗

Cloning and characterization of mr-s, a novel SAM domain protein, predominantly expressed in retinal photoreceptor cells.

BACKGROUND: Sterile alpha motif (SAM) domains are approximately 70 residues long and have been reported as common protein-protein interaction modules. This domain is found in a large number of proteins, including Polycomb group (PcG) proteins and ETS family transcription factors. In this work, we report the cloning and functional characterization of a novel SAM domain-containing protein, which is predominantly expressed in retinal photoreceptors and the pineal gland and is designated mouse mr-s (major retinal SAM domain protein). RESULTS: mr-s is evolutionarily conserved from zebrafish through human, organisms through which the mechanism of photoreceptor development is also highly conserved. Phylogenetic analysis suggests that the SAM domain of mr-s is most closely related to a mouse polyhomeotic (ph) ortholog, Mph1/Rae28, which is known as an epigenetic molecule involved in chromatin modifications. These findings provide the possibility that mr-s may play a critical role by regulating gene expression in photoreceptor development. mr-s is preferentially expressed in the photoreceptors at postnatal day 3-6 (P3-6), when photoreceptors undergo terminal differentiation, and in the adult pineal gland. Transcription of mr-s is directly regulated by the cone-rod homeodomain protein Crx. Immunoprecipitation assay showed that the mr-s protein self-associates mainly through the SAM domain-containing region as well as ph. The mr-s protein localizes mainly in the nucleus, when mr-s is overexpressed in HEK293T cells. Moreover, in the luciferase assays, we found that mr-s protein fused to GAL4 DNA-binding domain functions as a transcriptional repressor. We revealed that the repression activity of mr-s is not due to a homophilic interaction through its SAM domain but to the C-terminal region. CONCLUSION: We identified a novel gene, mr-s, which is predominantly expressed in retinal photoreceptors and pineal gland. Based on its expression pattern and biochemical analysis, we predict that mr-s may function as a transcriptional repressor in photoreceptor cells and in pinealocytes of the pineal gland.

Animals↗

High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels.

The association of mRNA expression levels of leptin receptors (long isoform: Lep-R(L) and short isoform: Lep-R(S)) in breast cancer tissue with patient prognosis was studied with special reference to the serum leptin level or the leptin mRNA level in tumor tissue. Lep-R(L), Lep-R(S) and leptin mRNA levels in breast cancer tissue (n = 91) were determined with a real-time PCR assay, and serum leptin levels in breast cancer patients (n = 67) with an enzyme-linked immunosorbent assay. Neither Lep-R(L) nor Lep-R(S) mRNA levels in tumor tissue were significantly associated with patient prognosis, but both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors were significantly (p < 0.01) associated with a poor prognosis. Multivariate analysis showed that a high level of both Lep-R (L) and Lep-R (S) mRNA in tumor tissue was a significant risk factor, independent of other risk factors. The subset analysis demonstrated that both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors were significantly associated with a poor prognosis for the subset of patients with high serum leptin or high intratumoral leptin mRNA levels but not in the subset of patients with low serum leptin or low intratumoral leptin mRNA levels. The association between both intratumoral Lep-R(L) and Lep-R(S) mRNA high tumors and a poor prognosis in the presence of high serum leptin or high intratumoral leptin mRNA levels seems to suggest that the leptin and Lep-R(L)/Lep-R(S) pathways are implicated in the growth stimulation of breast tumors. The well-established finding that obesity serves as a risk factor for relapse in breast cancer patients may thus be partially explained by the high serum leptin level seen in obese women.

Adult↗

Comparison of visual function after epiretinal membrane removal by 20-gauge and 25-gauge vitrectomy.

PURPOSE: To compare the efficacy and safety of 25-gauge vitrectomy with 20-gauge vitrectomy for macular pucker. DESIGN: Randomized clinical study. METHODS: Sixty-seven eyes (67 patients) with macular pucker were prospectively and randomly assigned to undergo 20-gauge vitrectomy or 25-gauge vitrectomy as a control group. Main outcome measurements consisted of best-corrected visual acuity (BCVA), mean induced astigmatism, total operation time, and postoperative complications. RESULTS: The mean BCVA at baseline and at one month and six months after surgery was 20/78, 20/62, and 20/42, respectively, in the 20-gauge group, and 20/85, 20/45, and 20/40 in the 25-gauge group. A significant difference in change in the logarithm of the minimal angle of resolution of BCVA between 20-gauge and 25-gauge was found at one month (-0.10 vs -0.269, P < .001), but not at six months (-0.327 vs -0.276, P > .01). CONCLUSIONS: If faster visual improvement is desired, 25-gauge vitrectomy may be preferable to 20-gauge vitrectomy for macular pucker.

Astigmatism↗

A novel vascular endothelial growth factor receptor 2 inhibitor, SU11248, suppresses choroidal neovascularization in vivo.

AIM: An oral, multitargeted receptor tyrosine kinase inhibitor, SU11248, inhibits vascular endothelial growth factor receptor 2 (VEG FR2, kinase domain receptor F1K1), platelet-derived growth factor receptor, stem cell factor receptor (Kit), and fetal liver tyrosine kinase 3. In this study, we administered SU11248 beyond the completion of an experimental choroidal neovascularization (CNV) model to determine whether CNV growth can be inhibited in vivo. METHODS: C57B6J mice were treated with daily oral administration (40, 80, and 150 mg/kg) of SU11248 during 5 days after diode laser endophotocoagulation and subjected to angiographic examination and histological analysis. RESULTS: Intensity of fluorescein leakage from the experimental CNV decreased significantly compared to the control eyes. Histological study also revealed that the volume of CNV membrane was significantly reduced in the SU11248-treated eyes. CONCLUSIONS: Oral administration of this compound is potentially beneficial in treating CNV caused by age-related macular degeneration (AMD) and other causal diseases. Considering the tolerance the clinical studies for malignant tumors previously demonstrated, further studies to evaluate the clinical efficacy of the drug for AMD might be indicated.

Administration, Oral↗

High expression of ubiquitin carboxy-terminal hydrolase-L1 and -L3 mRNA predicts early recurrence in patients with invasive breast cancer.

The present study investigated the mRNA expression level of ubiquitin c-terminal hydrolase (UCH)-L1 and -L3 in breast cancer tissue and aimed to elucidate its association with tumor characteristics and patient prognosis. UCH-L1 and UCH-L3 mRNA levels in invasive breast cancer (n = 100) were determined by a real-time polymerase chain reaction (PCR) assay and their relationship with various clinicopathological characteristics of breast tumors as well as patient prognosis were studied. UCH-L3 mRNA level was significantly upregulated in breast cancer tissue compared to adjacent normal breast tissue (P < 0.005), and UHC-L1 mRNA level also showed a non-significant increase in tumor tissue compared to adjacent normal breast tissue. Both UCH-L1 and UCH-L3 mRNA levels were significantly higher in high histological grade tumors than in low histological grade tumors (P < 0.001 and P < 0.005, respectively). High UCH-L1 mRNA level was significantly associated with negative estrogen receptor status (P < 0.05) and negative progesterone receptor status (P < 0.05). Patients with both UCH-L1 and UCH-L3 mRNA high tumors showed a significantly poorer prognosis than those in the UCH-L1 or UCH-L3 mRNA low group (P < 0.005). These observations that UCH-L3 mRNA level is upregulated in breast cancer tissue, and breast tumors with both UCH-L1 and UCH-L3 mRNA high expression are associated with a poor prognosis, suggest the possible involvement of UCH-L1 and UCH-L3 in the pathogenesis and progression of breast cancer.

Antigens, CD↗

Effects of peroxisome proliferator-activated receptor gamma and its ligand on blood-retinal barrier in a streptozotocin-induced diabetic model.

PURPOSE: To clarify whether endogenous peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligand, rosiglitazone, affect retinal leukostasis and the associated vascular leakage using an experimental diabetic model. METHODS: Diabetes was induced in heterozygous PPARgamma+/- mice and Brown Norway rats with an intraperitoneal streptozotocin (STZ) injection. Retinal leukostasis and leakage, quantified by concanavalin A (Con A) lectin perfusion labeling combined with a fluorophotometric dextran leakage assay, were investigated at 120 days in diabetic PPARgamma+/- and wild-type mice and at 21 days in diabetic rats receiving rosiglitazone or the vehicle. The retinal protein expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, and the intercellular adhesion molecule (ICAM)-1 were investigated by means of the ELISA assay. RESULTS: In the diabetic PPARgamma+/- mice, retinal leukostasis and leakage were greater than in the diabetic wild-type mice. In addition retinal leukostasis and leakage were suppressed by treatment with rosiglitazone in experimental diabetic rats. ELISA analysis revealed that the upregulated ICAM-1 expression in the diabetic rat retina was reduced by rosiglitazone treatment. CONCLUSIONS: An endogenous pathway involving PPARgamma provides protection against retinal leukostasis and retinal leakage in diabetes and treatment with PPARgamma specific ligands inhibits retinal leukostasis and retinal leakage in diabetic rats.

Animals↗

[Immediate breast reconstruction following to skin-sparing mastectomy].

Patients with breast cancer accompanied by extensive intraductal components or multiple tumors are not considered to be candidates for breast-conserving surgery. To improve post-operative quality of life of such patients, skin-sparing mastectomy with immediate reconstruction has been performed recently. We described our experience of skin-sparing mastectomy and areola-nipple-sparing mastectomy followed by immediate reconstruction with the use of a latissimus dorsi myocutaneous flap, a transverse rectus abdominis myocutaneous flap, and a deep inferior epigastric artery perforator flap. These operations appear to be oncologically safe when patients are selected carefully, and have a great benefit for the patients both aesthetically and psychologically.

Female↗

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

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

Antineoplastic Agents, Phytogenic↗

A familial case of pigmented paravenous retinochoroidal atrophy with asymmetrical fundus manifestations.

PURPOSE: To report two Japanese sibling cases with pigmented paravenous retinochoroidal atrophy (PPRCA) with asymmetrical manifestation. METHODS: A 33-year-old female and her 31-year-old brother were referred to our hospital. Funduscopic examination, angiography, and electroretinogram were performed. RESULTS: Both had retinal pigment epithelium atrophy with pigmentation along the retinal veins, which was consistent with PPRCA. The younger brother was more severely affected than his sister. Surprisingly, the extent and degree of the affected region was clearly different between both eyes of each patient. CONCLUSIONS: These findings have rarely been reported previously, and these cases stress the importance of considering gender, familial involvement, and variable manifestations of the disease in clinical care of PPRCA.

Adult↗

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

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

Adenoma↗