The surgical strategy and the molecular analysis of patients with parathyroid cancer.

Background: Parathyroid cancer is a rare endocrine tumor, and the prognostic factors for this cancer remain unclear. The standard therapy is en bloc resection of the primary tumor at the time of the initial operation. However, the clinical significance of prophylactic neck dissection (PND) in the management of parathyroid cancer has not yet been established. In this study, we investigated its clinical significance in patients with parathyroid cancer and the association of gene mutations with tumor progression.

Methods: A total of 12 patients with parathyroid cancer were treated and have been followed at Noguchi Thyroid Clinic and Hospital Foundation since 1977. In all, 11 patients were treated with the initial surgery for the cancer, and 1 patient underwent surgery for a metastatic lung lesion. Somatic and germ-line mutations of the HRPT2 and MEN1 were examined by polymerase chain reaction and automated DNA sequencing.

Results: En bloc resections of thyroid tissue were performed in 10 patients, and 1 patient underwent only parathyroidectomy with limited resection of the thyroid gland. PND was performed in eight patients, and no lymph node metastases were found in the histological specimens. Six of the eight patients had no evidence of the disease, and two had recurring disease (neck lymph node and lung in one patient and local, lung, and brain in another). PND was not performed in three patients, two of whom had no evidence of the disease and one with recurrence at the site of a regional lymph node. There were no significant differences in disease-free survival and cause-specific survival between the patients who underwent PND and the patients who did not (P = 0.98 and P = 0.32, respectively). Among the 12 patients with parathyroid cancer, 1 had a germ-line mutation of the HRPT2 at exon 7, codon 234, CGA (Arg) to TGA (Stop), and 1 patient had a tumor-specific mutation at exon 1, nucleotide 34-37 delAACA. Two of the four patients with recurrent disease had an HRPT2 gene mutation. MEN1 gene analysis revealed one somatic missense mutation at exon 2, codon 121, GTC (Val) to GAC (Asp) in one patient.

Conclusions: PND for patients with parathyroid cancer resulted in no evidence of lymph node metastasis and does not improve the prognosis. HRPT2 gene mutation may be associated with tumor recurrence.