title: Molecular Characteristics of Large Parathyroid Adenomas.
abstract: BACKGROUND
  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.
  
  
  METHODS
  We divided the parathyroid lesions into large (>7 g, i.e., LPTAs) and small (<7 g) adenomas. 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 parafibromin 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India. amit@sgpgi.ac.in.
authors.forename: Amit
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Roma
authors.initials: R
authors.lastname: Pradhan
authors.affiliation: Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Niraj
authors.initials: N
authors.lastname: Kumari
authors.affiliation: Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Narendra
authors.initials: N
authors.lastname: Krishnani
authors.affiliation: Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Shukla
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Gyan
authors.initials: G
authors.lastname: Chand
authors.affiliation: Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: A
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Agarwal
authors.affiliation: Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Verma
authors.affiliation: Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.
authors.forename: Saroj Kanta
authors.initials: SK
authors.lastname: Mishra
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D005260:Female; D037502:Galectin 3 / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010280:Parathyroid Glands / Q000378:metabolism* / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000032:analysis*; D043222:Ubiquitin Thiolesterase / Q000032:analysis*
chemical_list: D037502:Galectin 3; D025521:Tumor Suppressor Proteins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase