[Ectopic thyroid hormone producing tumor].
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Diagnosis, Differential↗
Biomedical subjects
Shin-ichi Murata
Publications and source records attributed to Shin-ichi Murata.
RET gene rearrangements (RET/PTC1 and RET/PTC3) in papillary thyroid carcinomas from an iodine-rich country (Japan).
BACKGROUND: The frequency of RET rearrangements (RET/PTC) in papillary thyroid carcinomas varies significantly according to geographic area, with the greatest incidence reported in the Belarus region, which is iodine-deficient and was contaminated severely after the Chernobyl reactor accident, and with the lowest incidence in iodine-rich, nonirradiated Japan. The authors investigated the prevalence of RET/PTC in a large number of thyroid tumors from Japanese patients. METHODS: Fresh and paraffin embedded tumor tissues from 215 Japanese patients were examined for RET rearrangements (RET/PTC1 and RET/PTC3) by means of reverse transcriptase-polymerase chain reaction analysis, with primers flanking the chimeric region, followed by direct-sequence analysis. RESULTS: RET/PTC was found only in papillary carcinomas and was not observed in other histologic types of thyroid tumors. The overall frequency of RET/PTC in papillary carcinomas was 28.4%, with a greater frequency in younger patients, including 41.9% of younger patients age < 20 years, 27.6% of patients age 20-40 years, and 24.8% of patients age > 40 years. Among the patients in these 3 age groups, the prevalence rate of RET/PTC1 was similar, but RET/PTC3 was observed most frequently among patients age < 20 years. When the tumors were grouped further according to histologic subtypes, the prevalence of RET/PTC3 was greater in solid/solid-follicular papillary carcinomas than in classic papillary carcinomas. CONCLUSIONS: The results indicated that RET/PTC may be useful as a specific molecular marker for papillary thyroid carcinomas. Furthermore, its incidence in such tumors was not low in Japanese patients, and it seemed to be associated with patient age. Therefore, the current results raise questions regarding the belief that the frequency of RET/PTC differs geographically and is especially low in Japan.
Adult↗
Stromal elastosis in papillary thyroid carcinomas.
Stromal elastosis, defined as dense aggregations of elastic fibers, is found in some neoplastic tissues especially in malignant tumors of the breast and lung. Although also found in thyroid tissue, stromal elastosis in thyroid neoplasms have received little attention. To clarify the histopathological significance of stromal elastosis in the thyroid, we examined neoplastic (n = 223) and hyperplastic (n = 82) thyroid tissues in conjunction with cancer tissues (n = 193) of various other organs. Stromal elastosis was observed as deposits of pale homogeneous material in hematoxylin and eosin stain, and distinctively highlighted by elastic-van Gieson's stain. On immunohistochemical examination, elastin and tropoelastin were confirmed in these deposits. Stromal elastosis was found in 66% of papillary thyroid carcinomas (PTCs), although it was not identified in other histological types of thyroid neoplasms. In PTCs, deposits of elastic fibers varied in size and shape, and were more frequently distributed in the periphery of the tumor tissue. The histological subtypes of PTC varied in prevalence of elastosis with the follicular variant's (9%) prevalence being significantly lower than that of the classical type (72%). The frequency of stromal elastosis in PTCs was very similar to the frequencies in breast and lung adenocarcinomas, and higher than the frequencies in carcinomas of other organs. In conclusion, our results suggest that stromal elastosis is a characteristic histological finding of PTCs, presumably associated with their growth pattern and/or histological architecture. It is, therefore, reasonable to propose that stromal elastosis is an ancillary feature in the histopathological diagnosis of PTCs.
Carcinoma, Papillary↗
Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia: a report of four cases with histochemical and immunohistochemical analyses.
We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia.
Adenocarcinoma↗
Application of cryotechniques with freeze-substitution for the immunohistochemical demonstration of intranuclear pCREB and chromosome territory.
Intranuclear localization of signal molecules and chromosome territories has become more attractive in relation to postgenomic analyses of cellular functions. Cryotechniques and freeze-substitution (CrT-FS) have been generally used for electron microscopic observation to obtain better ultrastructure and immunoreactivity. To investigate benefits of applying the CrT-FS method to immunostaining of intranuclear signal molecules and FISH for chromosome territories, we performed an immunohistochemical study of phosphorylated cAMP-responsive element binding protein (pCREB) in mouse cerebellar tissues and a FISH study of chromosome 18 territory in human thyroid tissues using various cryotechniques. The immunoreactivity of pCREB was more clearly detected without antigen retrieval treatment on sections prepared by the CrT-FS method than those prepared by the conventional dehydration method. In the FISH study, more definite probe labeling of the chromosome territory could be obtained on paraffin sections by the CrT-FS method without microwave treatment, although such labeling was not clear even with microwave treatment on sections prepared by the routine dehydration method. The CrT-FS preserved relatively native morphology by preventing shrinkage of nuclei, and produced better immunoreactivity. Because the reduction of routine pretreatments in the present study might reveal more native morphology, the CrT-FS method would be a useful technique for intranuclear immunostaining and FISH.
Animals↗
Immunolocalization of protein 4.1B/DAL-1 during neoplastic transformation of mouse and human intestinal epithelium.
Recently, we have reported that the protein 4.1B immunolocalization occurred only in matured columnar epithelial cells of normal rat intestines. This finding suggested that protein 4.1B expression could be examined for a possible change during neoplastic transformation of the intestinal mucosa. In the present study, we first present the distribution of mouse protein 4.1B in normal intestinal epithelial cells and tumor cells using the adenomatous polyposis coli (Apc) mutant mouse model. A low level of protein 4.1B expression coincided with the phenotypic transition to carcinoma. To examine the protein 4.1B expression in human intestinal mucosa, we used another antibody against an isoform of the human protein 4.1B, DAL-1 (differentially expressed adenocarcinoma of the lung). Human DAL-1 was also expressed in matured epithelial cells in human colons, with a definite expression gradient along the crypt axis. In human colorectal cancer cells, however, DAL-1 expression was not detected. These results suggest that mouse protein 4.1B and human DAL-1 might have a striking analogy of functions, which may be integrally involved in epithelial proliferation. We propose that loss of protein 4.1B/DAL-1 expression might be a marker of intestinal tumors, indicative of a tumor suppressor function in the intestinal mucosa.
Animals↗
Human dendritic cell lysosome-associated membrane protein expressed in lung type II pneumocytes.
Human dendritic cell LAMP (hDC-LAMP) is a unique member of the lysosome-associated membrane protein (LAMP) family with a tissue distribution initially described as restricted to major histocompatibility class II (MHC II) compartments of activated DC before the translocation of MHC II to the cell surface [Immunity 9 (1998) 325]. In this report, we show that hDC-LAMP is also expressed by lung type II pneumocytes, another cell type with constitutive expression of MHC II. A recombinant hDC-LAMP protein and a monospecific anti-hDC-LAMP polyclonal antibody were prepared. The antibody reacted specifically with hDC-LAMP sequences of hDC-LAMP protein expressed in transfected cells and with a 54 kDa protein of normal human lung tissue with properties corresponding to those of transgene expressed hDC-LAMP. Immunohistochemical analysis of hDC-LAMP in human lung showed its presence in alveolar type II epithelial cells (type II pneumocytes) as well as in cells in the interfollicular area of bronchus-associated lymph nodes, where interdigitating DCs are concentrated, and with lesser staining of alveolar macrophages. The native protein contained approximately 16% carbohydrates, most of which are sialyl N-linked oligosaccharides, with an acidic isoelectric point (pI 4.8). The restricted localization of this protein to lung type II pneumocytes and DCs is in contrast to hLAMP-1, which was present in many cell types of the lung and lymph node. Type II pneumocytes are known to express MHC II and the abundant expression of hDC-LAMP in these cells as well as in DCs suggests its possible relationship to specific MHC II related function(s) of DC and type II pneumocytes.
Antigens, CD↗
Mixed papillary adenocarcinoma and transitional cell carcinoma of the uterine cervix.
A mixed papillary adenocarcinoma and transitional cell carcinoma (MAcTcc) was discovered in the uterine cervix of a 38-year-old woman. A condylomatous papillary lesion was found in the uterine cervix during a colposcopic study and histopathological examination showed that the tumor was composed of two different neoplastic subtypes. One was an adenocarcinoma (AC) component showing papillary and tubular structure with endocervical and intestinal differentiation; the other was a transitional cell carcinoma (TCC) component showing papillary excrescence mimicking papillary TCC of urothelial origin. To characterize the tumor, an immunohistochemical study of cytokeratins (CK) was performed. The AC component showed immunoreactivities similar to conventional adenocarcinomas: positive immunoreactivity of low-molecular-weight cytokeratins 7, 8 and 19, and negative immunoreactivity of CK20 and high-molecular-weight cytokeratin (34betaE12). The lower epithelial layer of the TCC component showed different immunoreactivity, but the superficial epithelial layer had similar immunohistochemical findings to the AC component. These findings indicate that the TCC component had the cellular character of AC rather than that of TCC or squamous cell carcinomas. This is thought to be the first report of a MAcTcc of the uterine cervix.
Adenocarcinoma, Papillary↗
Expression of human pendrin in diseased thyroids.
We examined pendrin expression in various diseased thyroid tissues by immunohistochemistry (IHC) using antiserum raised against human pendrin and by real-time quantitative RT-PCR. In normal thyroids the antiserum reacted with the apical membrane of follicular cells and its immunoreactivity was faint. In Graves' thyroids, the IHC expression of pendrin appeared in a pattern similar to that of normal thyroids but it was more extensive and stronger, especially in areas showing marked proliferation of follicular cells. The immunoreactivities of pendrin in nodular goiters varied from case to case. In follicular adenomas, pendrin was localized in the follicle-forming parts of the tumor but was negative in trabecular parts. Pendrin was negative in all follicular carcinomas, papillary carcinomas, and in one case of medullary carcinoma. In quantitive mRNA analysis, the relative values of pendrin mRNA were significantly low in papillary carcinoma (p<0.01), whereas the values in other diseased thyroids were not significantly different from those in normal thyroids. These results suggest that pendrin may play a role in thyroid hormone production as the apical porter of chloride/iodide and investigation of pendrin leads to a better understanding of functional aspects of the iodine transportation system in thyroid diseases.
Carrier Proteins↗
The development of diabetes mellitus in Wistar rats kept on a high-fat/low-carbohydrate diet for long periods.
The present study was performed to determine the effect of long-term feeding with a high-fat/low-carbohydrate (HF/LC) diet on the onset of type-2 diabetes mellitus in normal rats. Male Wistar Imamichi rats were kept on a Control (carbohydrate 60%, fat 15%) or HF/ LC (carbohydrate 10%, fat 65%) diet for 16 mo. An intraperitoneal glucose tolerance test was performed once every 2 mo. Glucose tolerance was impaired 2 mo after the start of HF/LC diet feeding, accompanied by a decrease in the insulinogenic index. Along with time of HF/LC diet feeding, the glucose tolerance was further deteriorated with more serious impairment of insulin secretion and sensitivity. At the end of the experiment, 15 of 18 rats in the HF/LC group were diabetic, whereas only 4 of 17 rats in the Control group were diabetic. The present results demonstrate that longterm feeding with a HF/LC diet decreases the secretion and sensitivity of insulin, and induces diabetes mellitus in rats. Furthermore, long-term feeding with such a diet may produce adverse effects on the blood plasma lipid profile, with elevated levels of triglycerides, nonesterified fatty acids, total cholesterol, and reduced levels of high density protein cholesterol in the plasma.
Animals↗
Detection of underlying characteristics of nuclear chromatin patterns of thyroid tumor cells using texture and factor analyses.
BACKGROUND: Aspiration biopsy cytology of thyroid tumors has been used more frequently in recent times to differentiate between malignant and benign lesions. Chromatin patterns of the tumor cell nuclei are one of most important factors for cytologic diagnosis. The interpretation of nuclear chromatin patterns is subjective and more difficult than that of nuclear size or shape. In the present report, we investigated how to detect underlying chromatin characteristics of benign and malignant thyroid tumor cells by means of texture and factor analyses. METHODS: We employed a computer-aided system in which light microscopy was combined with an image processor and monochrome camera. Using this system, 100 randomly selected cells in a Papanicolaou stained, aspiration biopsy cytologic smear in each case of 39 benign and malignant thyroid tumor cases were digitized. We applied two-dimensional and higher texture analyses with the use of co-occurrence and run-length matrices to analyze the chromatin patterns. Factor analysis was used to determine whether a large number of independent variables actually measured one or more underlying common variables. RESULTS: According to parameters with high factor-loading values, the morphologic chromatin characters were classified into three categories according to heterogeneity, contrast, and homogeneity of chromatin patterns. On the basis of analyses with these morphologic categories, nuclei of papillary carcinoma showed higher contrast of chromatin patterns than did those of the benign group. Moreover, there was a variety of contrasting chromatin patterns among cells in each papillary carcinoma case in comparison with the benign group. In contrast, follicular carcinomas showed a significant difference in the standard deviation of factor 3, which indicated more monotonous chromatin patterns among cells in each follicular carcinoma case than in each benign case. CONCLUSION: We believe that this technique, using texture and factor analyses, is useful in the detection of underlying characteristics of nuclear chromatin patterns in aspiration biopsy cytology.
Adenocarcinoma, Follicular↗
Expression of thyroid transcription factor-1 in normal and neoplastic lung tissues.
The expression of thyroid transcription factor-1 in normal and neoplastic tissues and cell lines of the human lung was investigated using immunohistochemistry and in situ hybridization in conjunction with reverse transcription polymerase chain reaction. In normal lung tissues, immunoproducts of thyroid transcription factor-1 were observed in the nuclei of alveolar cells and bronchiolar cells. Interestingly, in distal bronchioles, immunohistochemistry and in situ hybridization revealed that thyroid transcription factor-1 was present not only in nonciliated cells (Clara cells) but also in ciliated cells and basal cells. In neoplastic tissues, thyroid transcription factor-1 was demonstrated in adenocarcinomas and small cell lung carcinomas with high frequency: 96% and 89% of cases, respectively. Thyroid transcription factor-1 was not detected in squamous cell carcinomas and large cell carcinomas. The strong immunoreactivity of thyroid transcription factor-1 or simultaneous expressions of thyroid transcription factor-1 and surfactant protein A tended to correlate with the differentiation phenotypes in adenocarcinomas; they were more frequently present in the well-differentiated type than were moderately and/or poorly differentiated types. By reverse transcription polymerase chain reaction, expression of thyroid transcription factor-1 messenger RNA was observed in squamous cell carcinomas in addition to in adenocarcinomas and small cell lung carcinomas, and this finding was confirmed in the cell lines from squamous cell carcinomas. Only one case of 99 adenocarcinomas that originated in various organs other than lung and thyroid immunohistochemically expressed thyroid transcription factor-1. Our results suggest that thyroid transcription factor-1 can play an important role for the maintenance and/or differentiation process in bronchiolar and alveolar cells. Thyroid transcription factor-1 expression associates with histologic types and/or differentiation of lung cancers and can be a valuable marker for the better understanding of their biological nature and pathological behavior.
Adenocarcinoma↗
Application of microscopic Forster resonance energy transfer to cytological diagnosis of the thyroid tumors.
We propose a novel application of microscopic Forster resonance energy transfer (FRET) to clinical cytological diagnosis based on sensitive measurements of distance changes between fluorescently labeled deoxyribose nucleic acid (DNA) molecules. We have employed the microscopic FRET imaging for investigation of six papillary carcinomas and eight benign cases. In each case the FRET images of 20 cells stained by the AT-specific donor Hoechst 33258 and the GC-specific acceptor 7-aminoactinomycin D were acquired and analyzed by texture analysis. We have not found significant difference of the mean FRET efficiency between the benign and malignant groups. On the other hand, the texture analysis revealed a significant difference of the intranuclear spatial distribution of FRET efficiencies between the benign and malignant groups. The results indicate that despite the similar average distance between the AT- and the GC-rich DNA segments in the papillary carcinomas and the benign cases, the former has more heterogeneous distribution of the AT- and the GC-rich DNA segments in nuclei compared to the benign groups. We have demonstrated that the FRET imaging is a helpful tool for the medical cytological diagnosis of human tumors by giving information on the chromatin topology on the scale below the resolution of conventional optical microscopes. (c) 2005 Society of Photo-Optical Instrumentation Engineers.
Artificial Intelligence↗
Unusual cytologic findings in low grade papillary transitional cell carcinoma.
OBJECTIVE: To describe cases of low grade papillary transitional cell carcinoma (LG-pTCC) with a low nuclear cytoplasmic (N/C) ratio and unusual cytologic patterns with many isolated, single neoplastic cells. STUDY DESIGN: We defined the following unusual cytologic findings as "isolated, single cell pattern": (1) numerous single cells sometimes with a few flat cell clusters; (2) very low N/C ratio; (3) angulation of cytoplasmic contour; (4) pale, homogeneous cytoplasm; (5) hyperchromatic nuclei with an uneven contour; (6) monotonous cytologic appearance; and (7) clear background. We studied 2,956 cytologic specimens of voided urine from 114 LG-pTCC patients at our university hospital during a 10-year period. RESULTS: Thirty-six specimens had the isolated, single cell pattern. The isolated, single cell pattern showed less celllular atypia than does the typical pattern of LG-pTCC. On histology the cases with the isolated, single cell pattern showed a papillary structure with an erosive surface and were composed of mildly atypical neoplastic cells with very low N/C ratios. CONCLUSION: Some LG-pTCCs show many single, atypical transitional cells.
Carcinoma, Papillary↗