We subjected the promoter regions of two genes residing at 11p, namely the tumour-suppressor gene WT1 (Wilms' tumour gene) (11p13) and the calcitonin gene (11p15.5), to methylation analysis in human sporadic colorectal cancer using genomic sequencing.
We investigated 11 cases of MMFC by immunohistochemistry and in situ hybridization (ISH) to analyse the structural features, the immunophenotypic profile and the calcitonin (CT) and thyroglobulin (TG) gene expression of the neoplasm.
Of 163 patients for whom follow-up data were obtained, 82 (50%) experienced recurrences of medullary thyroid carcinoma, including symptomatic recurrent tumors in 24 patients and elevated calcitonin levels alone in 54.
Periodic endocrine screening also was performed, by measuring the plasma calcitonin concentration after provocation with pentagastrin (0.5 microgram/kg intravenously) to assess its reliability for detecting the associated neoplasms.
The aim of this study was to evaluate clinical findings, surgical therapy, and outcome for 56 patients affected by PHPT among 249 MEN-IIa patients collected from 84 families assembled by the Groupe d'Etude des Tumeurs á Calcitonine (GETC, French CalcitoninTumors Study Group).
Immunohistochemically, there were no significant correlations between the outcome of the patients and the expression of calcitonin (CT), carcinoembryonic antigen (CEA), calcitonin gene-related peptide (CGRP), or chromogranin A (CgA) in the primary tumors, and there were no differences in expression of these antigens between the primary and the recurrent tumors.
Clinical data showed that 75% of the patients whose tumor carried ret mutation had tumor recurrence and/or increased serum calcitonin concentrations during the postsurgical follow-up period as opposed to 10% of the patients without mutations (P < 0.02, by chi2 analysis).
Site-specific methylation changes, as revealed by the use of methylation-sensitive restriction enzymes, have been reported to occur in the promotor region of the calcitonin gene in chronic myeloid leukemia as it progresses from the chronic phase to blast crisis, in non-Hodgkin's lymphoid neoplasms and in non-lymphocytic leukemia.
The variation in cellular content of immunoreactive calcitonin is interpreted as resulting from either an increased tumor growth rate or reduced ability to store peptide in a less differentiated tumor.
But immunohistochemical staining revealed vasoactive intestinal polypeptide and calcitonin only in a few cells, and it was still obscure what kinds of hormones were produced in this tumour.
Medullary thyroid carcinoma (MTC), a tumor arising from calcitonin-secreting C cells, appears in either a sporadic nonfamilial or a hereditary form as a component of a multiple endocrine neoplasia syndrome or familial non-multiple endocrine neoplasia MTC.
Serum obtained from the patient before his death contained elevated levels of both chromogranin A (2641 ng/mL; normal level, less than 20 ng/mL) and calcitonin (517 pg/mL; normal level, less than 200 pg/mL), suggesting that the patient's principal tumor was neuroendocrine in origin.
The proven power of DNA ploidy to predict mortality risk in medullary thyroid carcinoma (MTC) may be weakened when analyzed in conjunction with calcitonin immunoreactivity (CI) and amyloid staining (AS) of tumors.
These in vitro findings suggest that the combined use of glucocorticoids and calcitonin plays a beneficial role in the treatment of malignancy-associated hypercalcemia, since the steroid hormone can suppress PTHrP mRNA expression and release of bioactive PTHrP in certain PTHrP-producing tumors.
Immunocytochemistry for calcitonin and carcinoembryonic antigen as well as flow cytometry for DNA ploidy may be valuable techniques to assess prognosis of these tumors.
The tumor tissue from all 17 cases examined was found to exhibit calcitonin and CGRP immunoreactivity, and in 15 of the 17 cases the tumor tissue also contained GRP immunoreactivity.
Regulation of expression of the human calcitonin gene was found to differ between two tumor lines of different tissue origin, medullary thyroid carcinoma (TT line) and small-cell lung carcinoma (DMS53 line).
Calcitonin immunoreactivity and the amyloid content also provided prognostic information in multivariate analyses that adjusted for all the other factors mentioned above and in the full multivariate model, which in addition considered age, sex, heredity, stage of the disease, tumor size, and treatment.
However, no evidence could be found for CGRP gene expression in tumour tissue from the same patients as judged by immunocytochemistry or in-situ hybridization using CGRP cRNA probes.