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Parafibromin expression in breast cancer: a novel marker for prognostication?
  1. Sathiyamoorthy Selvarajan (sathiyaparamjo{at}
  1. Singapore General Hospital, Singapore
    1. Lang Hiong Sii
    1. Singapore General Hospital, Singapore
      1. Adrian Lee
      1. Singapore General Hospital, Singapore
        1. George Yip
        1. National University of Singapore, Singapore
          1. Boon Huat Bay
          1. National University of Singapore, Singapore
            1. Min Han Tan
            1. National Cancer Centre, Singapore
              1. Bin-Tean Teh
              1. Van Andel Research Institute, United States
                1. Puay-Hoon Tan (gpttph{at}
                1. Singapore General Hospital, Singapore


                  Objectives: Parafibromin, a novel protein product of HRPT2, is a recently identified tumor suppressor gene. Mutations of the HRPT2 gene are common in parathyroid carcinoma, and parathyroid carcinomas exhibit reduced protein expression. Parafibromin expression in breast cancer has not been previously studied. We aimed to determine the distribution of this protein in breast cancer tissues, and correlate its expression with conventional pathologic parameters.

                  Materials and methods: Tissue microarrays (TMAs) were constructed from archival paraffin embedded breast cancers diagnosed at the Department of Pathology, Singapore General Hospital. Sections cut from TMA blocks were subjected to immunohistochemistry. Immunopositivity for parafibromin and intensity-percentage scores were derived by blinded evaluation. Findings were correlated with clinicopathological parameters.

                  Results: A total of 163 breast cancers was assessed. Larger tumors were less likely to express parafibromin than smaller ones, with the association approaching statistical significance (p = 0.05). Staining intensity correlated inversely with tumor size (p = 0.016) and pathologic stage (p = 0.008); as did parafibromin intensity-percentage score with pathologic stage (p = 0.03), lymphovascular invasion (p = 0.03) and cerbB2 intensity-percentage score (p = 0.04).

                  Conclusion: Parafibromin in breast cancer, as in parathyroid tumors, appears to have tumor suppressor functions, with loss of protein expression being associated with adverse pathologic parameters. These findings may indicate a potential role of parafibromin as a prognostic marker in breast cancer.

                  • immunohistochemistry
                  • infiltrative breast carcinoma
                  • parafibromin
                  • tumor suppressor

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