Immunohistochemical detection of cell cycle regulators, Fhit protein and apoptotic cells in parathyroid lesions (original) (raw)
Related papers
Human Pathology, 1994
Samples of normal, hyperplastic, and neoplastic parathyroid tissues were analyzed for proliferative activity to determine (1) whether a higher number of proliferating cells were detectable in adenoma and hyperplasia versus normal tissues; (2) whether there was a difference in the number of proliferating cells in adenoma versus hyperplasia; and (3) whether there was a relationship between nodularity and proliferative rate in both adenoma and hyperplasia. Fornudin-fixed, paraffin-embedded tissue from 21 patients with parathyroid adenoma and 10 patients with hyperplasia (two primary, six secondary, and two tertiary) was analyzed by immunohistochemistry with the monoclonaf antibody PC10 to proliferating cell nuclear antigen (PCNA) and, in a subset of cases, with Ki-67 (MIB 1) as markers of cell proliferation. The results were that (1) no proliferating cells were found in normal glands or residual rim of "suppressed" parathyroid tissue; (2) the most intense proliferative activity was confined to nodular areas in both adenomas (57% nodular) and hyperplasias (80% nodular); (3) when fields of highest number of labeled nuclei were chosen, PCNA counts were higher in adenomas than in hyperplasias in both nodular and diffuse areas (P < .05); and (4) the number of nuclei immunoreactive for Ki-67 (MIB-1) was consistently and proportionally lower (range, 13% to 45%; mean, 32%) than the number of those immunoreactive for PCNA, although the nodular pattern was maintained. These findings demonstrate that nodules within parathyroid adenomas and hyperplasias contain subpopulations of cells with a consistently higher proliferative rate than nonnodular areas. Cells within these nodules may be more likely to develop genetic abnormalities that have been observed in hypetplastic and neoplastic parathyroid tissues. HUM PA-THOL
Loss of heterozygosity of selected tumor suppressor genes in parathyroid carcinoma. Discussion
Surgery, 2008
Background. The histologic diagnosis of parathyroid carcinoma (PC) is challenging. We evaluated a large PC series for loss of heterozygosity (LOH) of selected tumor suppressor genes with histopathologic correlation. Methods. Among 2,238 patients explored for primary hyperparathyroidism (PHP), the cytoarchitectural parameters of 60 patients with surgical and/or pathologic suspicion for PC were examined by 1 pathologist. PC was diagnosed with $1 of the following: extracapsular, thyroidal, perineural, or angiolymphatic invasion; atypical mitoses; or metastasis. LOH was determined for PC or parathyroid adenoma (PA) using a panel of 12 tumor suppressor gene loci. Fractional allelic loss (FAL) was calculated as the percentage of loci with LOH divided by the number of informative loci. Results. PC occurred in 0.8% of patients with PHP. Angiolymphatic (68%) and soft tissue (47%) invasion were the most common histologic findings. For PC, mean FAL was 32% vs 14% for PA (P = .03). Among informative cases, LOH was found at the HRPT2 locus in 7 of 14 (50%) PC vs 0 of 7 (0%) PA; the Rb locus in 4 of 15 (27%) PC vs 0 of 8 (0%) PA; the MEN1 locus in 6 of 15 (40%) PC vs 1 of 8 (13%) PA; and the 1p35.2--36.2 (including p21) locus in 8 of 13 (62%) PC vs 2 of 6 (33%) PA. Conclusion. In PC diagnosed by strict histologic criteria, LOH for a selected tumor suppressor gene panel was common. Specific tumor suppressor genes such as HRPT2 demonstrated LOH in up to 50% of PC, while not seen in any PA. Evaluation of LOH may be useful for the definitive diagnosis of PC. (Surgery 2008;144:949-55.) From the Divisions of Endocrine Surgery a and Pathology,
Loss of heterozygosity of selected tumor suppressor genes in parathyroid carcinoma
Surgery, 2008
Background. The histologic diagnosis of parathyroid carcinoma (PC) is challenging. We evaluated a large PC series for loss of heterozygosity (LOH) of selected tumor suppressor genes with histopathologic correlation. Methods. Among 2,238 patients explored for primary hyperparathyroidism (PHP), the cytoarchitectural parameters of 60 patients with surgical and/or pathologic suspicion for PC were examined by 1 pathologist. PC was diagnosed with $1 of the following: extracapsular, thyroidal, perineural, or angiolymphatic invasion; atypical mitoses; or metastasis. LOH was determined for PC or parathyroid adenoma (PA) using a panel of 12 tumor suppressor gene loci. Fractional allelic loss (FAL) was calculated as the percentage of loci with LOH divided by the number of informative loci. Results. PC occurred in 0.8% of patients with PHP. Angiolymphatic (68%) and soft tissue (47%) invasion were the most common histologic findings. For PC, mean FAL was 32% vs 14% for PA (P = .03). Among informative cases, LOH was found at the HRPT2 locus in 7 of 14 (50%) PC vs 0 of 7 (0%) PA; the Rb locus in 4 of 15 (27%) PC vs 0 of 8 (0%) PA; the MEN1 locus in 6 of 15 (40%) PC vs 1 of 8 (13%) PA; and the 1p35.2--36.2 (including p21) locus in 8 of 13 (62%) PC vs 2 of 6 (33%) PA. Conclusion. In PC diagnosed by strict histologic criteria, LOH for a selected tumor suppressor gene panel was common. Specific tumor suppressor genes such as HRPT2 demonstrated LOH in up to 50% of PC, while not seen in any PA. Evaluation of LOH may be useful for the definitive diagnosis of PC. (Surgery 2008;144:949-55.) From the Divisions of Endocrine Surgery a and Pathology,
Immunohistochemical Profile of Parathyroid Tumours: A Comprehensive Review
International Journal of Molecular Sciences
Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022). Loss of parafibromin indicates a greater probability of malignant course and should trigger the search for inherited or somatic CDC73 mutations. Aberrant immunophenotype is characterised by a set of markers that are lost (parafibromin), down-regulated (e.g., APC protein, p27 protein, calcium-sensing receptor) or up-regulated (e.g., proliferation activity by Ki-67 exceeding 5%) in parathyroid carcinoma compared to benign parathyroid disease. Aberrant immuno...
Gene Expression of Parathyroid Tumors
Cancer Research, 2004
Parathyroid tumors are heterogeneous, and diagnosis is often difficult using histologic and clinical features. We have undertaken expression profiling of 53 hereditary and sporadic parathyroid tumors to better define the molecular genetics of parathyroid tumors. A class discovery approach identified three distinct groups: (1) predominantly hyperplasia cluster, (2) HRPT2/carcinoma cluster consisting of sporadic carcinomas and benign and malignant tumors from Hyperparathyroidism-Jaw Tumor Syndrome patients, and (3) adenoma cluster consisting mainly of primary adenoma and MEN 1 tumors. Gene sets able to distinguish between the groups were identified and may serve as diagnostic biomarkers. We demonstrated, by both gene and protein expression, that Histone 1 Family 2, amyloid β precursor protein, and E-cadherin are useful markers for parathyroid carcinoma and suggest that the presence of a HRPT2 mutation, whether germ-line or somatic, strongly influences the expression pattern of these 3...
Molecular Characteristics of Large Parathyroid Adenomas
Introduction The clinical entity of large parathyroid adenomas (LPTAs) has not been well defined. It is speculated that LPTAs would have biochemical, histological, and molecular characteristics different from small adenomas. Our study aimed to find out occurrence of atypia and carcinomas in large parathyroid lesions and the presence of distinct molecular abnormalities in LPTAs. Materials and methods We divided the parathyroid lesions into large ([7 g, i.e., LPTAs) and small (\7 g) ade-nomas. We performed parafibromin, APC (adenomatous polyposis coli), galectin 3, and PGP9.5 (protein gene product 9.5) analysis by immunohistochemistry in adenomas without atypia, atypical adenomas, and carcinomas. Results Mean serum calcium, alkaline phosphatase, and intact PTH were significantly higher in large parathyroid tumor group. The presence of both atypical adenoma and carcinoma was higher in large parathyroid tumor group. There was higher percentage of atypia in patients with LPTAs[10 g (33 %), and 68 % of tumors showed at least one marker suggestive of malignancy in this group. Detailed analysis of immunohistochemical features of LPTA [10 g revealed that six patients showed complete loss of parafibromin immunoreactivity (out of these four showed atypia), while seven showed partial loss. In histopathologically proven malignancy (n = 9), six patients showed complete loss of parafi-bromin staining, 5 (55 %) APC negativity, and 45 % showed both galectin 3 and PGP9.5 positivity. Three out of these showed all IHC markers s/o malignancy, and all of them had evidence of metastases or recurrence. 32 % of atypical adenoma and 13 % of atypical adenoma showed complete loss of parafibromin staining, however none developed metastases or recurrence in follow-up (median follow-up 40 months). Loss of parafibromin staining (complete or partial) was higher in LPTA group (56 %) than that in small adenoma (39 %); however, it was not statistically significant. APC, galectin 3, and PGP9.5 markers suggestive were higher in LPTA group but were not significant. Conclusion LPTAs may show some morphological and immunohistochemical features suggestive of malignancy and can be considered a separate entity. However, the immunohistochemical markers are unable to clearly segregate those LPTAs that may show premalignant potential. Further, we would like to recommend that LPTAs showing complete parafibromin loss together with atypia should be kept under close follow-up.