Defining a molecular phenotype for benign and malignant parathyroid tumors.
BACKGROUND
It is frequently difficult to establish histologically whether a parathyroid tumor is a parathyroid carcinoma, parathyromatosis, or an atypical adenoma. The authors asked whether these tumors have a distinctive molecular profile, whether benign tumors could be distinguished from malignant tumors, and whether parathyromatosis is a low-grade parathyroid carcinoma or is benign tissue that can invade other organs.


METHODS
Samples of parathyroid carcinoma, atypical adenoma, parathyromatosis, parathyroid adenoma, and hyperplasia were obtained for tissue microarray studies. The molecular expression of genes involved in parathyroid tumor progression (HRPT2 ["parafibromin"], galectin-3, Ki-67, Rb, p27, and mdm-2) was investigated by immunohistochemistry.


RESULTS
Complete loss of parafibromin expression was seen in 5 of 16 (31.3%) parathyroid carcinomas; all parathyromatosis, atypical adenomas, adenomas, and hyperplasia stained positive for parafibromin. Loss of Rb expression was seen in 5 (33.3%) of 15 parathyroid carcinomas and 1 (7.1%) of 14 parathyroid hyperplasias; all parathyromatosis, atypical adenomas, and adenomas stained positive. Galectin-3 stained strongly positive in 14 (93.3%) of 15 parathyroid carcinomas, and positive in 3 (18.7%) of 16 cases of parathyromatosis, 2 (100%) of 2 atypical adenomas, 1 (5.6%) of 18 adenomas, and 2 (14.3%) of 14 hyperplasias. The Ki-67 proliferative index was high in 9 (60%) of 15 parathyroid carcinomas, 1 (6.7%) of 15 cases of parathyromatosis, 1 (5.6%) of 18 adenomas, and no atypical adenomas or hyperplasia. P27 and mdm-2 protein expression did not differ appreciably among the tumor types.


CONCLUSIONS
No single diagnostic marker currently determines whether a parathyroid tumor is a parathyroid carcinoma, but loss of parafibromin and Rb expression, and overexpression of galectin-3, generally distinguish parathyroid carcinoma from other parathyroid tumors. Parathyromatosis does not appear to be a low-grade parathyroid carcinoma.
Fernandez-Ranvier
Gustavo G
GG
Department of Surgery, University of California at San Francisco, San Francisco, California 94143-1674, USA.
Khanafshar
Elham
E
Tacha
David
D
Wong
Mariwil
M
Kebebew
Electron
E
Duh
Quan-Yang
QY
Clark
Orlo H
OH
D000236:Adenoma / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000175:diagnosis; D005260:Female; D037502:Galectin 3 / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010279:Parathyroid Diseases / Q000175:diagnosis; D010282:Parathyroid Neoplasms / Q000175:diagnosis*; D010641:Phenotype; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
D014408:Biomarkers, Tumor; C454900:CDC73 protein, human; D037502:Galectin 3; D019394:Ki-67 Antigen; D025521:Tumor Suppressor Proteins