Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis.
We studied 45 patients with typical and 8 with atypical parathyroid adenomas as well as 20 with parathyroid carcinomas. Clinical, pathological, and molecular analyses were conducted on all adenomas. Clinical data were analyzed for 20, histopathologic slides for 16, and tissue specimens for 8 patients with carcinoma. Molecular expression profiles were investigated by immunohistochemistry (IHC) for Ki-67, p53, mdm2, p21, Bcl-2, cyclin D1, and p27 on paraffin-embedded tissues arrayed on tissue microarrays. Trabecular growth and vascular, capsular, and soft-tissue invasion were characteristic of parathyroid carcinomas but not of typical adenomas. No adenomas recurred. Seventy-four percent of carcinomas recurred, most in the neck. Seventy-nine percent of patients with such illness died of disease after an indolent, multiply recurrent course responsive to repeated resections; the 5-year survival rate was 50%. High Ki-67 proliferative index was seen in 2% of adenomas and 25% of carcinomas, whereas p27 expression was present in 80% of adenomas and 18% of carcinomas. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), was observed in 76%, 29%, and 0% of typical and atypical adenomas and carcinomas, respectively. The complexity of molecular phenotypes increased with tumor aggressiveness. Parathyroid carcinoma is an aggressive disease with a propensity for multiple recurrences. It is characterized by capsular, vascular, and soft-tissue invasion. Recurrence portends poor outcome. Molecular markers, Ki-67 and p27, may distinguish parathyroid carcinoma from adenoma. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), appears to be unique to nonmalignant parathyroid tumors, and multimarker phenotypes are more complex in carcinomas.
Stojadinovic
Alexander
A
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Hoos
Axel
A
Nissan
Aviram
A
Dudas
Maria E
ME
Cordon-Cardo
Carlos
C
Shaha
Ashok R
AR
Brennan
Murray F
MF
Singh
Bhuvanesh
B
Ghossein
Ronald A
RA
D000236:Adenoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics / Q000556:secondary; D018797:Cell Cycle Proteins / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D016591:Histocytological Preparation Techniques; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010282:Parathyroid Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen