Papillary Carcinoma of the Breast (PC-B) Lacks Evidence of RET Rearrangements Despite Morphological Similarities to Papillary Thyroid Carcinoma (PTC)
O Hameed, A Perry, H Banerjee, X Zhu, JA Pfeifer. University of Alabama School of Medicine, Birmingham; Washington University School of Medicine, St. Louis
Background: PC-B can occasionally display nuclear features similar to those seen in PTC. In addition, there are a few reports describing primary breast carcinomas resembling the tall-cell variant of PTC. The aim of this study was to evaluate a series of PC-B for the prevalence of the histologic features that mimic those of PTC and to access whether these reflect the presence of the RET chromosomal rearrangements characteristic of PTC.
Design: A series of 33 intraductal/intracystic PC-B with or without associated invasive carcinoma was histologically reviewed to confirm the diagnosis and evaluate for the presence or absence of morphological features of PTC including the characteristic nuclear features (nuclear overlap, grooves, clearing, and inclusions) and cytological features of the tall-cell or columnar variants. RET rearrangements were studied in a subset of these cases by FISH and RT-PCR. Paired probes localizing to the centromeric and telomeric ends of the RET gene on chromosome 10 were developed from human BAC clones and used in a break-apart FISH approach. These probes were validated in a cell line harboring the RET-PTC1 rearrangement and in 2 cases of PTC (where split green and red signals were identified in 42-45% of nuclei) and in 17 normal breast and thyroid control tissues (in which split signals were seen in only 1-3% of nuclei). Published RT-PCR primers designed to detect RET-PTC1, RET-PTC2, and RET-PTC3 fusions were used in both single round and nested PCR approaches.
Results: Nuclear overlap, grooves, and clearing were at least focally identified in 23 (70%), 12 (36%), and 9 (27%) cases, respectively, while none of the cases displayed intranuclear inclusions. Cytological features resembling the tall-cell or columnar variants of PTC were focally identified in 1 (3%) and 2 (6%) cases, respectively. Four of 19 tested cases displayed split FISH signals in a low percentage of cells (range: 9-11%), and were considered equivocal for RET rearrangement. These 4 cases, as well as another 15 cases with amplifiable RNA (out of 22 tested cases) were all negative for the 3 RET-PTC fusions evaluated by RT-PCR.
Conclusions: Although PC-B can show, at least focally, cytologic and nuclear features reminiscent of PTC, there is no evidence that they share the most common RET-PT rearrangements characteristic of PTC.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 12, Tuesday Afternoon