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Expression of parathyroid hormone-related protein (PTHrP) in normal and abnormal human parathyroid tissues
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RELATIONSHIP BETWEEN THE IMMUNOHISTOCHEMICAL EXPRESSION OF PARATHYROID HORMONE RELATED PROTEIN, TUMOR WEIGHTS AND SERUM CALCIUM LEVEL IN RENAL CELL CARCINOMAS wGotoh,a. T. Oeawa. S. &&awa. 0. Matsumato. S. Maeda. S. a Department of Urology, 2nd Department of Pathology, 3rd Division Department of Medicine, Kobe University, Kobe. Japan. Parathyroid hormone-related protein (PTHrP) is the predominant causative factor of humoral hypercalcemia of Recently, on cDNA analysis. PTHrP malignancy (HHM). was shown to consist of 141 amino acids and to have a significant homology with PTH in the N-terminal region. PTHrP has also been demonstrated in normal human tissues; in several endocrine organs, lactating mammary gland, placenta, and skin keratinocytes. Using a PTHrPsspecific monoclonal antibody (MAb). 4B3, we investigated the immunohistochemical localization of PTHrP in a series of formaline-fixed and paraffittembedded sections of 54 human renal cell carcinomas obtained at oneration. PTHrP was detected in 50 of 54 renal ceil carcinoma Histopathologisally, the high ttrade, the tissues (926%~). granular~ cell subtypes and the iubuhtr types of iettai cell carcinomas were tended IO be more strongly positive than Moreover, the group with strong PTHrP. thd othdr typds. tumors characteristically immunoreactivity nnd weighty In torn1 cases, showed high serum calcium level. however, there was no significant correlation between the degree of immunohistochemical staining and the patients’ serum calcium level. In conclusion, we found that PTHrP was commonly observed in renal cell carcinomas, and that HHM occurred when the total amount of PTHrP exceeded the homeostatic mechanisms of calcium metabolism.
EXPRESSICN 0% PARATHYROID HOHMONE-RELATED PROTEW (PTHrP) IN NORMAL AND ABNORMAL HUMAN PARATHYROlD .. TISSUES. &. Kttazowa. M. Fukase. S. Kitazowa. S. Maeda. T. Puntg gnd A. Kobavashi 3rd Division, Department of Medicine, 2nd Department of Pathology, Kobe University School of Medicine and Kuma Hospital , Kobe , Japan Porathyroid hormone-related protein (PTHrF). a maior factor responsible for humoral hypercalcetnia OF malignancy (HHM), has been reported to be produced in several nonneoplastic tissues and endocrine ctgans including parathyroid glands. It remains, however, unclear that which cells in parathyroid glaud can express and produce PTHrP. We have reported the expression aeti iuca!isatitn OCPTHrP in the porothyroid glands from normal subjects and primary hyperparathyroidism (adenomo) and in hyperplastic glands from patients with chronic renal failure (secondary hyperparathyroidisml. by light and electron microscopic immunohistochemistry with an onti-hPTHrP monoclonol antibody 483 (Cancer. 1990) ond in situ hvbridization usine BrdU&belled cDNA -probe (Histochemistry: 1989). Twelve of I4 normal glands, I3 of 19 adenomas. 16 of 18 cases of secondary hyperparathyroidism represented positive immunoreactivity for 4B3. Immunostaining of 483 was completely extinguished by preabsorption with ihe excess of hPTHrP( l-34). In normal parathyroids, the ratio of positive cells tended to increase in relation to the age of the subjects. PTHrP-immunoreoctivity was mainly observed in typical oxiphil cells and some transitional ceils, but scarcely seen in chief cells and woter clear cells. By immunoelectron microscopy, secretary gronules sized lOOA in diameter were demonstrotrd in the cytoplasm obundant of mitochondrio. Transcripts of PTHrP were clearly demonstrated in consistency with PTHrP-immunoreactivity by on in situ hybridization usinn semi-serial sections. Conclusively; we first demonstrated that PTHrP and PTHrP mRNA were found to be located characteristically in oxiphil cells regardless of the pothogenesis of parathyroid The presence of PTHrP might connect with the glands. phenotypic differentiation of oxiphil cells.
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PARATHYROID HORMONE-RELATED PROTEIN (PTHrP) IN CALCIFYING EPITHELIOMA AND MENINGIOMA.
2nd Department of Pathology, 3rd Division Department of Medlcinc Kobe University, Kobe. Japan. Parathvroid hormone.related arotein tPTHrP1 is a major factor- of humoral hypcrcal&mia of‘ maliguancy (##Mt. Recently, PTHrP was found to be trresent antonu normal human tis&tcs and is thought to pliy an import&tr role in the differentiation of kcratinocytes and local calcium transport. In our previous immunehistochemical studv amtbPTHrP mtxioclonrl antibody, PTHrP was locsied in the skin epidermis. skin ttpparatus. endocrine organs. plaecnte and rraehnold villi -(Cancer. 1991). Calcifying cpithelioma (Pilomatricoma) and meningioma are common tumors derived from skin apparatus and araehnoid villi respectively. Both tumors are characterized by frequent calcification. In our current study, we investigated the immunohistechemical localization of PTHrP in a series of formalin-fixed and aaraffine-,---.------embedded surgically resected calcifying epitheliomas and meningiomas. ltt calcifying epitheliomas. PTHrP was positive in all cases (16/16l. Histologically. shadow cells were more strongly positive than basophiiic cells. In cases with ossifications, stromol fibroblasts were also positive for PTHrP. In mcninaiomas, PTHrP was uositive in oil crises f8/81 of paammoma type, 73 % (618) of ‘meningotheliomotous type. 25 (l/41 of transitional type and non (O/S) of fibrous tvae. Accordingly. there is a didthtotive correlation between tie presence of PTHrP and rotio of calcification. In conclusion, immunohistochemical localization of PTHrP correlated well with the presence of calcification and psammoma body in calcifying epithelioma and meningiomo.
Abstract wit
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RELATIONSHIP BETWEEN THE IMMUNOHISTOCHEMICAL EXPRESSION OF PARATHYROID HORMONE RELATED PROTEIN, TUMOR WEIGHTS AND SERUM CALCIUM LEVEL IN RENAL CELL CARCINOMAS wGotoh,a. T. Oeawa. S. &&awa. 0. Matsumato. S. Maeda. S. a Department of Urology, 2nd Department of Pathology, 3rd Division Department of Medicine, Kobe University, Kobe. Japan. Parathyroid hormone-related protein (PTHrP) is the predominant causative factor of humoral hypercalcemia of Recently, on cDNA analysis. PTHrP malignancy (HHM). was shown to consist of 141 amino acids and to have a significant homology with PTH in the N-terminal region. PTHrP has also been demonstrated in normal human tissues; in several endocrine organs, lactating mammary gland, placenta, and skin keratinocytes. Using a PTHrPsspecific monoclonal antibody (MAb). 4B3, we investigated the immunohistochemical localization of PTHrP in a series of formaline-fixed and paraffittembedded sections of 54 human renal cell carcinomas obtained at oneration. PTHrP was detected in 50 of 54 renal ceil carcinoma Histopathologisally, the high ttrade, the tissues (926%~). granular~ cell subtypes and the iubuhtr types of iettai cell carcinomas were tended IO be more strongly positive than Moreover, the group with strong PTHrP. thd othdr typds. tumors characteristically immunoreactivity nnd weighty In torn1 cases, showed high serum calcium level. however, there was no significant correlation between the degree of immunohistochemical staining and the patients’ serum calcium level. In conclusion, we found that PTHrP was commonly observed in renal cell carcinomas, and that HHM occurred when the total amount of PTHrP exceeded the homeostatic mechanisms of calcium metabolism.
EXPRESSICN 0% PARATHYROID HOHMONE-RELATED PROTEW (PTHrP) IN NORMAL AND ABNORMAL HUMAN PARATHYROlD .. TISSUES. &. Kttazowa. M. Fukase. S. Kitazowa. S. Maeda. T. Puntg gnd A. Kobavashi 3rd Division, Department of Medicine, 2nd Department of Pathology, Kobe University School of Medicine and Kuma Hospital , Kobe , Japan Porathyroid hormone-related protein (PTHrF). a maior factor responsible for humoral hypercalcetnia OF malignancy (HHM), has been reported to be produced in several nonneoplastic tissues and endocrine ctgans including parathyroid glands. It remains, however, unclear that which cells in parathyroid glaud can express and produce PTHrP. We have reported the expression aeti iuca!isatitn OCPTHrP in the porothyroid glands from normal subjects and primary hyperparathyroidism (adenomo) and in hyperplastic glands from patients with chronic renal failure (secondary hyperparathyroidisml. by light and electron microscopic immunohistochemistry with an onti-hPTHrP monoclonol antibody 483 (Cancer. 1990) ond in situ hvbridization usine BrdU&belled cDNA -probe (Histochemistry: 1989). Twelve of I4 normal glands, I3 of 19 adenomas. 16 of 18 cases of secondary hyperparathyroidism represented positive immunoreactivity for 4B3. Immunostaining of 483 was completely extinguished by preabsorption with ihe excess of hPTHrP( l-34). In normal parathyroids, the ratio of positive cells tended to increase in relation to the age of the subjects. PTHrP-immunoreoctivity was mainly observed in typical oxiphil cells and some transitional ceils, but scarcely seen in chief cells and woter clear cells. By immunoelectron microscopy, secretary gronules sized lOOA in diameter were demonstrotrd in the cytoplasm obundant of mitochondrio. Transcripts of PTHrP were clearly demonstrated in consistency with PTHrP-immunoreactivity by on in situ hybridization usinn semi-serial sections. Conclusively; we first demonstrated that PTHrP and PTHrP mRNA were found to be located characteristically in oxiphil cells regardless of the pothogenesis of parathyroid The presence of PTHrP might connect with the glands. phenotypic differentiation of oxiphil cells.
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PARATHYROID HORMONE-RELATED PROTEIN (PTHrP) IN CALCIFYING EPITHELIOMA AND MENINGIOMA.
2nd Department of Pathology, 3rd Division Department of Medlcinc Kobe University, Kobe. Japan. Parathvroid hormone.related arotein tPTHrP1 is a major factor- of humoral hypcrcal&mia of‘ maliguancy (##Mt. Recently, PTHrP was found to be trresent antonu normal human tis&tcs and is thought to pliy an import&tr role in the differentiation of kcratinocytes and local calcium transport. In our previous immunehistochemical studv amtbPTHrP mtxioclonrl antibody, PTHrP was locsied in the skin epidermis. skin ttpparatus. endocrine organs. plaecnte and rraehnold villi -(Cancer. 1991). Calcifying cpithelioma (Pilomatricoma) and meningioma are common tumors derived from skin apparatus and araehnoid villi respectively. Both tumors are characterized by frequent calcification. In our current study, we investigated the immunohistechemical localization of PTHrP in a series of formalin-fixed and aaraffine-,---.------embedded surgically resected calcifying epitheliomas and meningiomas. ltt calcifying epitheliomas. PTHrP was positive in all cases (16/16l. Histologically. shadow cells were more strongly positive than basophiiic cells. In cases with ossifications, stromol fibroblasts were also positive for PTHrP. In mcninaiomas, PTHrP was uositive in oil crises f8/81 of paammoma type, 73 % (618) of ‘meningotheliomotous type. 25 (l/41 of transitional type and non (O/S) of fibrous tvae. Accordingly. there is a didthtotive correlation between tie presence of PTHrP and rotio of calcification. In conclusion, immunohistochemical localization of PTHrP correlated well with the presence of calcification and psammoma body in calcifying epithelioma and meningiomo.
Abstract wit
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