MYB-NFIB Gene Fusion Is Present in Mammary Adenoid Cystic Carcinoma (ACC) and Cylindroma, Two Morphologically Similar Entities
Timothy M D'Alfonso, Jessica Padilla, Sandra J Shin. Weill Cornell Medical College, New York, NY
Background: Mammary ACC is a rare type of breast carcinoma which despite having a triple-negative and basal-like phenotype, has a favorable prognosis. Salivary gland ACCs are characterized by a fusion gene involving MYB and NFIB, resulting from a t(6;9)(q22-23;p23-24) translocation. This translocation results in the overexpression of MYB, and activation of oncogenic genes. This genomic alteration has recently been detected in 6 cases of mammary ACC. In addition, this translocation has been identified in dermal cylindromas. Primary mammary cylindroma, although rare, morphologically resembles ACC, but behaves in a benign fashion. In this study, we aimed to determine the frequency of MYB-NFIB fusion in a large series of mammary ACCs, as well as confirm the presence of this fusion in dermal cylindromas, which we used as a surrogate for mammary cylindroma.
Design: 31 cases of mammary ACC and 7 cases of dermal cylindroma were identified. Slides were reviewed and the diagnoses were confirmed. Formalin-fixed, paraffin-embedded tissue was available for each case. All tumors were screened by RT-PCR for the most common MYB-NFIB fusions, including MYB exon 14 linked to NFIB exon 8c, exon 9, or exon 8a, as well as additional fusion transcript variants which have previously been described.
Results: MYB-NFIB fusion transcript(s) were detected in 21 of 31 (68%) cases of mammary ACC and 5 of 7 dermal cylindromas. The transcript involving MYB exon 14 linked to NFIB exon 8c was present in 19 cases of mammary ACC and all 5 cases of cylindroma. In 6 cases of mammary ACC, additional MYB-NFIB fusion transcripts were detected, whereas in all 5 dermal cylindromas, one fusion transcript was present. There was no correlation between MYB-NFIB fusion status and specific morphologic features of mammary ACC such as nuclear grade, solid pattern, or frequency of mitotic figures.
Conclusions: MYB-NFIB gene fusion is present in the majority of mammary ACC and dermal cylindromas, providing evidence that these morphologically similar tumors also share common molecular features, despite behaving different clinically. The overexpression of MYB protein may prove to be a therapeutic target in ACC, and immunohistochemical detection of MYB may serve as a useful diagnostic marker in distinguishing mammary ACC from other breast lesions.
Monday, March 19, 2012 1:00 PM
Poster Session II # 77, Monday Afternoon