Prognostic Significance of p27Kip1, Ki-67, and CRTC1-MAML2 Fusion Transcript in Mucoepidermoid Carcinoma: A Molecular and Clinicopathologic Study of 101 Cases

Miyabe, Satoru; Okabe, Mitsukuni; Nagatsuka, Hitoshi; Hasegawa, Yasuhisa; Inagaki, Atsushi; Ijichi, Kei; Nagai, Noriyuki; Eimoto, Tadaaki; Yokoi, Masashi; Shimozato, Kazuo; Inagaki, Hiroshi

doi:10.1016/j.joms.2009.03.021

Cited by 68 publications

(54 citation statements)

References 31 publications

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“…Moreover, all low-grade tumors were positive for the CRTC1-MAML2 gene fusion, whereas only three of the 13 high-grade mucoepidermoid carcinomas were fusion-positive. 7,12,[19][20][21] The remaining 10 fusion-negative, high-grade tumors were also negative for the EWSR1-POU5F1 fusion previously identified in high-grade mucoepidermoid carcinomas. 22 These findings support the notion that low-grade mucoepidermoid carcinomas are fusion-positive and genetically stable tumors with few genomic imbalances.…”

Section: Discussionmentioning

confidence: 68%

“…[4][5][6][7] Nevertheless, all tumors with histologic appearances defined as mucoepidermoid carcinoma are considered malignant. 8 Although efforts have been made to identify clinically useful biomarkers for grading and prognostication [9][10][11][12] there is yet no unifying concept on how to classify mucoepidermoid carcinomas.…”

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confidence: 99%

“…17,18 Several studies have now confirmed the initial report by Behboudi et al 19 demonstrating that the CRTC1-MAML2 fusion primarily occurs in low-grade mucoepidermoid carcinomas with a favorable clinical outcome. 12,13,20,21 A second gene fusion involving the sarcoma-associated EWSR1 gene and the stem cell regulator POU5F1 was recently identified in mucoepidermoid carcinomas with a more immature morphology compared with MAML2 positive tumors. 22 Except for the CRTC1-MAML2 fusion, little is known about other genomic rearrangements of importance for the genesis and progression of mucoepidermoid carcinoma.…”

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confidence: 99%

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Genomic profiles and CRTC1–MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma

et al. 2013

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Mucoepidermoid carcinoma is the most common salivary gland malignancy, and includes a spectrum of lesions ranging from non-aggressive low-grade tumors to aggressive high-grade tumors. To further characterize this heterogeneous group of tumors we have performed a comprehensive analysis of copy number alterations and CRTC1-MAML2 fusion status in a series of 28 mucoepidermoid carcinomas. The CRTC1-MAML2 fusion was detected by RT-PCR or fluorescence in situ hybridization in 18 of 28 mucoepidermoid carcinomas (64%). All 15 low-grade tumors were fusion-positive whereas only 3 of 13 high-grade tumors were fusion-positive. Highresolution array-based comparative genomic hybridization revealed that fusion-positive tumors had significantly fewer copy number alterations/tumor compared with fusion-negative tumors (1.5 vs 9.5; P ¼ 0.002). Twelve of 18 fusion-positive tumors had normal genomic profiles whereas only 1 out of 10 fusionnegative tumors lacked copy number alterations. The profiles of fusion-positive and fusion-negative tumors were very similar to those of low-and high-grade tumors. Thus, low-grade mucoepidermoid carcinomas had significantly fewer copy number alterations/tumor compared with high-grade mucoepidermoid carcinomas (0.7 vs 8.6; Po0.0001). The most frequent copy number alterations detected were losses of 18q12.2-qter (including the tumor suppressor genes DCC, SMAD4, and GALR1), 9p21.3 (including the tumor suppressor genes CDKN2A/B), 6q22.1-q23.1, and 8pter-p12.1, and gains of 8q24.3 (including the oncogene MAFA), 11q12.3-q13.2, 3q26.1-q28, 19p13.2-p13.11, and 8q11.1-q12.2 (including the oncogenes LYN, MOS, and PLAG1). On the basis of these results we propose that mucoepidermoid carcinoma may be subdivided in (i) low-grade, fusion-positive mucoepidermoid carcinomas with no or few genomic imbalances and favorable prognosis, (ii) high-grade, fusion-positive mucoepidermoid carcinomas with multiple genomic imbalances and unfavorable prognosis, and (iii) a heterogeneous group of high-grade, fusion-negative adenocarcinomas with multiple genomic imbalances and unfavorable outcome. Taken together, our studies indicate that molecular genetic analysis can be a useful adjunct to histologic scoring of mucoepidermoid carcinoma and may lead to development of new clinical guidelines for management of these patients.

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Section: Discussionmentioning

confidence: 68%

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Genomic profiles and CRTC1–MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma

et al. 2013

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“…This observation may appropriately temper recent enthusiasm for exploiting HPV detection as a relevant biomarker when dealing with MECs. Indeed, the finding that the MAML2 translocation correlates with tumor grade supports the view that MAML2 status, not HPV status, may prove to be a much more promising prognostic marker for patients with MEC [12,21,22]. …”

Section: Discussionmentioning

confidence: 68%

“…With MECs in particular, the genetic profile may modulate tumor grade in ways where certain alterations may elude detection if case selection is too restricted. As one example, the MAML2 rearrangement is known to be much more common in low grade than high grade MECs [12,21,22]. Second, our analysis included documentation of MAML2 status.…”

Section: Discussionmentioning

confidence: 99%

Mucoepidermoid Carcinoma Does Not Harbor Transcriptionally Active High Risk Human Papillomavirus Even in the Absence of the MAML2 Translocation

Bishop

Yonescu

Batista

et al. 2014

Head and Neck Pathol

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High risk human papillomavirus (HPV) is firmly established as an important cause of oropharyngeal carcinoma. Recent studies have also implicated HPV as a cause of mucoepidermoid carcinoma (MEC)-a tumor of salivary gland origin that frequently harbors MAML2 translocations. The purpose of this study was to determine the prevalence of transcriptionally active HPV in a large group of MECs and to determine whether HPV infection and the MAML2 translocation are mutually exclusive events. Break-apart fluorescence in situ hybridization for MAML2 was performed on a tissue microarray containing 92 MECs. HPV testing was performed using RNA in situ hybridization targeting high risk HPV mRNA E6/E7 transcripts. Of the 71 MECs that could be evaluated by FISH, 57 (80 %) harbored the MAML2 rearrangement. HPV was not detected in any of the 57 MECs that contained a MAML2 rearrangement, in any of the 14 MECs that did not contain the rearrangement, or in any of the 21 MECs where MAML2 status was unknown. High risk HPV does not appear to play any significant role in the development of MEC. It neither complements nor replaces MAML2 translocation in the tumorigenesis of MEC.

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Uncommon Tumors of the Oral Cavity and Adjacent Structures

Bar‐Ad¹,

Tuluc²,

Cognetti³

et al. 2012

Textbook of Uncommon Cancer

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Prognostic Significance of p27Kip1, Ki-67, and CRTC1-MAML2 Fusion Transcript in Mucoepidermoid Carcinoma: A Molecular and Clinicopathologic Study of 101 Cases

Cited by 68 publications

References 31 publications

Genomic profiles and CRTC1–MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma

Genomic profiles and CRTC1–MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma

Mucoepidermoid Carcinoma Does Not Harbor Transcriptionally Active High Risk Human Papillomavirus Even in the Absence of the MAML2 Translocation

Uncommon Tumors of the Oral Cavity and Adjacent Structures

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