Immunohistochemical Staining of Thyroidectomy Specimens for PTEN Can Aid in the Identification of Patients with Cowden Syndrome.
Justine A Barletta, Andrew M Bellizzi, Jason L Hornick. Brigham and Women's Hospital, Boston, MA
Background: Cowden syndrome (CS) is an autosomal dominant disorder with germline mutation of PTEN characterized by the development of multiple hamartomas and carcinomas of the thyroid, breast and uterus. Recognition of CS is important so that cancer screening and genetic counseling can be initiated. Pathologic findings in thyroidectomy specimens suggestive but not specific for CS include multiple adenomatous nodules and follicular adenomas, with or without follicular carcinoma or papillary thyroid carcinoma. The aim of our study was to determine if immunohistochemical staining for PTEN could aid in the identification of CS in patients with these pathologic findings.
Design: We studied 24 thyroidectomy specimens from patients with a known history of CS or with pathologic findings that raised the possibility of CS. Immunohistochemistry for PTEN was performed on all cases (rabbit monoclonal antibody, clone 138G6, Cell Signaling, 1:100 dilution). Assessment of PTEN expression was performed by a pathologist blinded to the clinical history and recorded as follows: intact expression in all lesional nodules, complete loss of expression in all lesional nodules, or focal loss of expression, with some nodules showing intact expression and others showing complete loss of expression.
Results: Ten cases showed loss of PTEN expression (five complete and five focal) and 14 cases showed intact expression. Of the 10 cases that showed loss of PTEN expression, seven patients were clinically confirmed to have CS (five showed complete loss of staining and two showed focal loss). Two additional patients had clinical findings strongly suggestive of CS, although PTEN mutational testing was not performed. One case had a clinical history that was not suggestive of CS and no further testing was pursued. Of the 14 cases that showed intact PTEN expression, none had CS by clinical history or genotyping. Two patients had PTEN testing that was negative, one had PTEN testing with equivocal results, nine had clinical examinations that were not suggestive of CS and no further testing was pursued, and two patients had no follow-up information available.
Conclusions: Immunohistochemical staining of thyroidectomy specimens for PTEN can aid in the identification of patients with CS. Loss of PTEN expression, either complete or focal, appears to be both sensitive and specific for CS, although the molecular mechanism underlying heterogeneous loss of PTEN expression is unknown. These findings warrant further evaluation of PTEN staining in thyroids from a larger cohort of patients with and without CS.
Monday, February 28, 2011 8:30 AM
Platform Session: Section H 1, Monday Morning