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International Journal of Surgical Pathology
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RET/PTC Rearrangement Occurring in Primary Peritoneal Carcinoma

Richard Flavin, FRCPath

Department of Histopathology, Trinity College Medical School, Dublin, Ireland, flavinr{at}tcd.ie

Gerhard Jackl, PhD

Institute of Molecular Radiobiology, GSF-National Research Centre for Environment and Health, Neuherberg, Germany

Stephen Finn, PhD, FRCPath

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Paul Smyth, PhD

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Martina Ring

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Esther O'Regan, PhD, BDS

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Susanne Cahill, PhD

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Kristian Unger, PhD

Institute of Molecular Radiobiology, GSF-National Research Centre for Environment and Health, Neuherberg, Germany

Karen Denning, MSc

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Jinghuan Li, MSc

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Sinead Aherne, BSc

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Giovanni Tallini, MD

Department of Pathology, Bologna University School of Medicine, Bologna, Italy

Eoin Gaffney, MD

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

J.J. O'Leary, MD, DPhil

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

Horst Zitzelsberger, PhD

Institute of Molecular Radiobiology, GSF-National Research Centre for Environment and Health, Neuherberg, Germany

Orla Sheils, PhD

Department of Histopathology, Trinity College Medical School, Dublin, Ireland

RET/PTC rearrangements are initiating events in the development of a significant proportion of papillary thyroid carcinomas. Activated RET/PTC mutations are thought to be restricted to thyroid disease, but this study proposes that these events may also occur in nonthyroid tumors. A total of 57 nonthyroid papillary tumors were examined for RET/PTC rearrangements using interphase fluorescence in situ hybridization, Taqman reverse transcriptase polymerase chain reaction, and immunohistochemistry. Taqman single nucleotide polymorphism detection was used to analyze for expression of mutated BRAF T1799A. In all, 20% (3/15) of primary peritoneal carcinoma had detectable RET/PTC1 rearrangements by all 3 methodologies. A further case of similar histotype had an alternate RET/ PTC rearrangement. No RET/PTC1 rearrangements were detected in the remaining tumor cohort. All 57 tumors were homozygous for wild-type BRAF. The results indicate that RET/PTC rearrangements occur in a small subset of nonthyroid papillary tumors. These rearrangements may not be directly implicated in tumor growth; rather representing "passenger" mutations reflecting RET instability in secondary tumor subclones.

Key Words: RET • RET/PTC1 • peritoneal serous carcinoma • fluorescence in situ hybridization (FISH) • reverse transcriptase polymerase chain reaction (RT-PCR)

This version was published on June 1, 2009

International Journal of Surgical Pathology, Vol. 17, No. 3, 187-197 (2009)
DOI: 10.1177/1066896908329593
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