RET/PTC Rearrangement Occurring in Primary Peritoneal Carcinoma

• Published in: International journal of surgical pathology Vol. 17; no. 3; pp. 187 - 197
• Main Authors: Flavin, Richard, Jackl, Gerhard, Finn, Stephen, Smyth, Paul, Ring, Martina, O'Regan, Esther, Cahill, Susanne, Unger, Kristian, Denning, Karen, Jinghuan Li, Aherne, Sinead, Tallini, Giovanni, Gaffney, Eoin, O'Leary, J.J., Zitzelsberger, Horst, Sheils, Orla
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-06-2009
• Subjects: Aged; Aged, 80 and over; Biomarkers - analysis; Carcinoma - genetics; Carcinoma, Papillary - genetics; Female; Gene Rearrangement; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Middle Aged; Oncogene Proteins, Fusion - genetics; Peritoneal Neoplasms - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins c-ret - genetics; Reverse Transcriptase Polymerase Chain Reaction; RET; RET/PTC1; peritoneal serous carcinoma; reverse transcriptase polymerase chain reaction (RT-PCR); fluorescence in situ hybridization (FISH)
• ISSN: 1066-8969; 1940-2465
• DOI: 10.1177/1066896908329593

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.