title: Parafibromin, galectin-3, PGP9.5, Ki67, and cyclin D1: using an immunohistochemical panel to aid in the diagnosis of parathyroid cancer.
abstract: BACKGROUND
  Parathyroid cancer is rare. Differentiating parathyroid carcinoma from degenerative changes at histopathology can be difficult and studies investigating the value of single immunohistochemical markers have had variable results. In this study we aimed to investigate whether a panel of immunohistochemistry markers could aid the diagnosis of parathyroid cancer.
  
  
  METHODS
  All cases of parathyroid cancer at our institution from 1998 to 2012 were identified retrospectively. Cases were classified as definite cancers (those with evidence of metastatic spread) or histological cancers (those with features of carcinoma without evidence of metastasis). Controls with benign parathyroid disease were included for comparison. Immunohistochemistry for parafibromin, galectin-3, PGP9.5, Ki67, and cyclin D1 was analysed by an experienced endocrine pathologist.
  
  
  RESULTS
  There were 24 cases and 14 benign adenomas. Four cases had evidence of metastatic spread and 20 were diagnosed on histological criteria alone. Sixteen of the 24 cases had further surgery with ipsilateral thyroid lobectomy and 15 also had a prophylactic level VI lymph node dissection. Apart from one patient with distant metastases at presentation, none developed recurrence at follow-up (median = 38 months). Immunohistochemistry results associated with parathyroid cancer were seen in 11/24 parafibromin, 13/24 galectin-3, 8/24 PGP9.5, 5/24 Ki67, and 2/24 cyclin D1. None of the controls had immunohistochemical staining suggestive of cancer. Nineteen of the 24 patients had at least one immunohistochemical result associated with parathyroid cancer (sensitivity 79 %, specificity 100 %). Cyclin D1 did not suggest malignancy in any case that did not already have another abnormal marker, and so did not add value to the panel in this study.
  
  
  CONCLUSIONS
  A panel of immunohistochemistry (PGP9.5, galectin-3, parafibromin, and Ki67) is better than any single marker and can be used to supplement classical histopathology in diagnosing parathyroid cancer.
authors.affiliation: Newcastle Upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK, petertruran@gmail.com.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Truran
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Johnson
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bliss
authors.forename: Thomas W J
authors.initials: TW
authors.lastname: Lennard
authors.forename: Sebastian R
authors.initials: SR
authors.lastname: Aspinall
mesh_terms: D000236:Adenoma / Q000737:chemistry* / Q000175:diagnosis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000175:diagnosis* / Q000556:secondary; D016022:Case-Control Studies; D019938:Cyclin D1 / Q000032:analysis; D005260:Female; D037502:Galectin 3 / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D010282:Parathyroid Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000473:pathology; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000032:analysis; D043222:Ubiquitin Thiolesterase / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C454900:CDC73 protein, human; D037502:Galectin 3; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C482860:UCHL1 protein, human; D019938:Cyclin D1; D043222:Ubiquitin Thiolesterase