CRTC1-MAML2 and CRTC3-MAML2 fusions have been associated with favorable clinicopathological features of mucoepidermoid carcinomas. However, the significance of the MAML2 gene split has not been fully clarified. In the present study, 95 mucoepidermoid carcinomas (paraffin-embedded materials) were analyzed for CRTC1-MAML2 and CRTC3-MAML2 fusions by RT-PCR and for the MAML2 gene split by FISH. Quantitative RT-PCR for the CRTC1-MAML2 transcript was performed in selected cases. MLL gene involvement, which has been reported in some leukemia cases, was examined by FISH in fusion partner-unknown cases. CRTC1-MAML2 and CRTC3-MAML2 fusions were detected in 37 and 6 cases, respectively. The MAML2 gene split was detected in 62 cases, which included all CRTC1/3-MAML2 fusion-positive cases. The level of CRTC1-MAML2 transcript expression was highly variable, and its clinicopathological impact was unclear. The MLL gene split was not detected. Mucoepidermoid carcinomas negative for CRTC1/3-MAML2 and positive for the MAML2 gene split (n = 19) showed favorable clinicopathological tumor features similar to those positive for CRTC1/3-MAML2 fusions. Compared with negative cases (n = 33), mucoepidermoid carcinomas positive for the MAML2 split (n = 62) were associated with lower patient age, a mild female predilection, a smaller tumor size, less frequent nodal metastasis, a lower clinical stage, a lower histological grade, and longer overall and disease-free survival. The MAML2 gene split emerged as an independent prognostic factor for both overall and disease-free survival in multivariate prognostic analysis. The presence of the MAML2 gene split defines a distinct mucoepidermoid carcinoma subset that is associated clinicopathologically with favorable tumor features. (Cancer Sci 2013; 104: 85-92) M ucoepidermoid carcinomas represent 5% of all salivary gland tumors and 20% of salivary malignancies.(1,2) A subset of these carcinomas has been associated with a recurring chromosomal translocation, t(11;19)(q21;p13), which generates a fusion protein composed of the N-terminal of cAMP response element-binding protein (CREB)-regulated transcription coactivator 1 (CRTC1), also called MECT1, TORC1 or WAMP1, and the C-terminal of mastermind-like gene 2 (MAML2).(3-6) Recent data suggest that CRTC1-MAML2 induced-activation of CREB is critical for cell transformation.(5,6) CTCR1-MAML2 fusion has been detected in 40-80% of primary salivary gland mucoepidermoid carcinomas, and we and other research groups have shown that the fusion gene is associated with a distinct tumor subset with an indolent clinical course. and in Nakayama et al. (12) we reveal that CRTC3-MAML2 fusion-positive mucoepidermoid carcinoma cases have an excellent prognosis. These findings suggest that both CRTC1-MAML2 and CRTC3-MAML2 fusions may be associated with mucoepidermoid carcinoma cases with favorable clinicopathological tumor features. (13) CRTC1/3-MAML2 fusions have been detected using an RT-PCR technique, assuming that exon 1 of CRTC1/3 genes is fused to exons 2-5 of th...

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Background Metaplastic carcinoma of the breast consists of both invasive ductal carcinoma and metaplastic carcinoma. This rare subtype of cancer has a poor prognosis. The development of metaplastic breast cancer and relationship with BRCA1 are not well known. Here, we report a rare case of germline BRCA1 mutation-positive breast cancer with chondroid metaplasia. Case presentation A 39-year-old Japanese woman with a family history of breast cancer in her mother and ovarian cancer in her maternal grandmother consulted at our hospital with a left breast mass. Needle biopsy for the mass was performed, leading to a diagnosis of invasive breast cancer with chondroid metaplasia. We performed left mastectomy + sentinel lymph node biopsy + tissue expander insertion and replaced with a silicone implant later. Pathological examination revealed that the patient had triple-negative breast cancer. Four courses of doxorubicin+ cyclophosphamide therapy were performed as adjuvant therapy after surgery. We performed genetic counseling and genetic testing, and the results suggested the germline BRCA1 mutation 307 T> A (L63*). She has currently lived without a relapse for 2 years post-surgery. Conclusions There have been only 6 cases of metaplastic breast carcinoma with germline BRCA1 mutations including our case. Patients with BRCA1 mutations may develop basal-like subtypes or M type of triple-negative breast cancer besides metaplastic breast cancers.