Immunohistochemical localization of parathyroid hormone-related protein (PTHrP) and serum PTHrP in normocalcemic patients with oral squamous cell carcinoma.

Published on Sep 1, 2005in Odontology2.634
· DOI :10.1007/S10266-005-0049-6
Makoto Tsuchimochi10
Estimated H-index: 10
(The Nippon Dental University),
Ayako Kameta4
Estimated H-index: 4
(The Nippon Dental University)
+ 1 AuthorsMasataka Katagiri5
Estimated H-index: 5
(The Nippon Dental University)
Sources
Abstract
Cancer cells produce parathyroid hormone-related protein (PTHrP) in the early phase of malignancy development, before hypercalcemia occurs. The relationship between PTHrP and the clinicopathologic features of oral squamous cell carcinoma is poorly understood. We studied 60 patients (43 men, 17 women; mean age, 64.8 ± 11.2 years) with primary oral squamous cell carcinoma, from whom pretreatment biopsy specimens were obtained. We examined the relationship among immunohistochemical PTHrP expression, serum PTHrP levels, clinical characteristics of the tumor, and histopathologic aspects of the tumor. The mean calcium concentration for the 60 patients was 9.1 ± 0.4 mg/dl. No patients had laboratory evidence of hypercalcemia before treatment. Six patients had serum levels of C-terminal (C)-PTHrP higher than the normal level of 55.3 pmol/l. There were no significant differences in serum C-PTHrP levels according to TNM stages. Abundant positive immunoreactivity for anti-PTHrP (1-34) antibody was recognized diffusely in the whole cytoplasm of many tumor cells. Anti-PTHrP (38-64) antibody staining tended to localize as small granules in the cytoplasm, especially close to the nuclear periphery. There was no correlation between the serum C-PTHrP concentration and the intensity of either immunostain. The intensity of PTHrP was proportionally related to the degree of differentiation or extent of keratinization (P < 0.05) and the histologic malignancy grade of the tumor (P < 0.05), when using antibody against PTHrP (1-34), but not when using antibody against PTHrP (38-64). Serum C-PTHrP levels did not correlate with the intensity of cellular PTHrP expression and characteristics of the tumor at the initial patient visit. The fragment that includes PTHrP (1-34) may be involved in the differentiation of oral squamous cell carcinoma. The differences between immunoreactivities may have been due to differing tissue malignancies and the use of different antibodies. The results suggest the need for caution when interpreting immunoreactivities of PTHrP in malignancies.
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References74
Newest
#1Akio Hiraki (Okayama University)H-Index: 44
#2Hiroshi Ueoka (Okayama University)H-Index: 36
Last. Mine Harada (Okayama University)H-Index: 78
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BACKGROUND Parathyroid hormone-related protein (PTH-rP) is a major cause of tumor-induced hypercalcemia (TIH) and frequently is found to be elevated in serum of patients with TIH. In the current study, the authors examined the usefulness of PTH-rP measurement at the time of first presentation in the follow-up of lung carcinoma patients with TIH. METHODS The authors retrospectively studied 23 of 1149 lung carcinoma patients who were found to have TIH at the time of first presentation for the corr...
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#1Masayasu Iwase (Showa University)H-Index: 17
#2Youichi Kurachi (Showa University)H-Index: 1
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Humoral hypercalcemia of malignancy (HHM) is one of the most common metabolic complications associated with cancer. A retrospective study of hypercalcemia in patients with squamous cell carcinoma of the oral cavity was undertaken. All patients were periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dl of the correction for serum albumin concentration. The serum levels of parathyroid hormone related protein (PTH-rP...
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#4Makoto Ohori (Kitasato University)H-Index: 43
BACKGROUND Parathyroid hormone-related protein (PTHrP) has been shown to be the principal cause of humoral hypercalcemia associated with renal cell carcinoma (RCC). Recent studies have demonstrated that the amino-terminal region of PTHrP has growth factor-like activities, suggesting it may play a role in the development of RCC. In this study, expression of the carboxy-terminal region of PTHrP was assessed immunohistochemically and its significance in predicting the prognosis of RCC was studied. ...
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#1Minoru Nishihara (Nagasaki University)H-Index: 2
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The purpose of the present study was to clarify the relationship of parathyroid hormone-related protein (PTHrP) to the oncogenesis and progression of colorectal adenocarcinoma. A total of 108 colorectal tumours, including 12 adenomas, six adenocarcinomas in adenomas, and 90 adenocarcinomas, were studied. Immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) techniques were used to evaluate the expression of PTHrP. Positivity of immunostaining f...
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Emerging evidence suggests that parathyroid hormone-related peptide (PTHrP) serves as a regulator of the development and/or differentiation of a number of organs, including endochondral bone, the tooth, and the mammary gland. Although disruption of the PTHrP gene by homologous recombination results in a lethal chondrodystrophy, PTHrP-knockout mice that have been rescued by the transgenic replacement of the peptide in cartilage display abnormalities in ectodermally derived structures including th...
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Parathyroid hormone (PTH)-related protein (PTHrP)-knockout mice die at birth with a chondrodystrophic phenotype characterized by premature chondrocyte differentiation and accelerated bone formation, whereas overexpression of PTHrP in the chondrocytes of transgenic mice produces a delay in chondrocyte maturation and endochondral ossification. Replacement of PTHrP expression in the chondrocytes of PTHrP-knockout mice using a procollagen II-driven transgene results in the correction of the lethal s...
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#1Yasuo Okada (The Nippon Dental University)H-Index: 6
#2Makoto Tsuchimochi (The Nippon Dental University)H-Index: 10
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Malignancy-associated hypercalcemia (MAH) often occurs in patients with squamous cell carcinoma of the lung, esophagus, oral cavity, and pharynx as well as those with other histopathologic malignancies, such as breast cancer, renal cell carcinoma and adult T-cell leukemia. We often encounter MAH in patients with terminal oral cancer. Parathyroid hormone related peptide (PTHrP) is considered the most likely cause of MAH. The aim of our study was to investigate whether the serum concentration of P...
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▪ Abstract Parathyroid hormone-related protein (PTHrP) is the agent responsible for humoral hypercalcemia of malignancy. Its pathogenic role in this syndrome is well established, and attention has focused in recent years on the elucidation of the roles played by PTHrP in normal developmental and adult physiology. This review focuses on studies of the past two years: (a) elucidation of the posttranslational processing pattern of PTHrP, the mechanisms of action of the various secretory forms of PT...
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Abstract Background Non–small-cell lung carcinoma immunoreactivity for parathyroid hormone-related protein has been associated with increased survival in female patients but not in male patients. The current investigation attempted to substantiate this finding in 2 new patient groups. Methods Patients were divided into groups with and without immunoreactivity for a carboxyl-terminal parathyroid hormone-related protein epitope assessed in deparaffinized sections by a blinded observer. One group i...
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