Wednesday, August 11, 2010

TTF1 expression in normal lung neuroendocrine cells and related tumors: immunohistochemical study comparing two different monoclonal antibodies

Abstract  
Thyroid transcription factor-1 (TTF1) regulates lung morphogenesis and differentiation, and its immunohistochemical expression
is used for identifying lung neoplasms. The 8G7G3/1 antibody has been used in previous studies, but a different and more sensitive
anti-TTF1 antibody, named SPT24, has become commercially available. Since the immunohistochemical expression of TTF1 in normal
lung neuroendocrine (NE) cells has not been previously investigated and its utility in the diagnosis of lung NE tumors is
a controversial issue, we studied the TTF1 expression in normal adult and fetal lungs, in 83 pulmonary NE neoplasms, in 131
non-lung NE tumors and in 36 metastases from these neoplasms using these two antibodies. A TTF1 immunoreactivity was demonstrated
in normal fetal and adult NE cells when using the SPT24 clone. Conversely, using the 8G7G3/1 antibody, only rare fetal neuroendocrine
cells were TTF1 positive while adult NE cells were negative. The SPT24 clone identified TTF1 expression in more carcinoids,
most of them peripherally located, and poorly differentiated NE carcinomas than the 8G7G3/1 clone. Non-pulmonary well-differentiated
NE tumors were negative for both antibodies. Among the 45 non-pulmonary poorly differentiated NE carcinomas 11% were positive
for 8G7G3/1 and 18% for SPT24. TTF1 expression in metastases perfectly reflected that detected in the related primary tumors.
Our results indicate that the SPT24 antibody is more sensitive than the 8G7G3/1 clone for labeling lung carcinoids and it
appears particularly useful in detecting peripheral neoplasms. In addition, the expression of TTF1 in normal NE cells suggests
a possible role for the transcription factor in their development and differentiation.

  • Content Type Journal Article
  • DOI 10.1007/s00428-010-0954-0
  • Authors
    • Stefano La Rosa, Department of Pathology, Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy
    • Anna Maria Chiaravalli, Department of Pathology, Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy
    • Claudia Placidi, Department of Human Morphology, University of Insubria, Varese, Italy
    • Nikolaos Papanikolaou, Department of Human Morphology, University of Insubria, Varese, Italy
    • Michele Cerati, Department of Pathology, Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy
    • Carlo Capella, Department of Pathology, Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy
    • Journal Virchows Archiv
    • Online ISSN 1432-2307
    • Print ISSN 0945-6317

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