Mammalian mastermind like 2 11q21 gene rearrangement in bronchopulmonary mucoepidermoid carcinoma

Achcar, Rosane De Oliveira Duarte; Nikiforova, Marina N.; Đačić, Sanja; Nicholson, Andrew G.; Yousem, Samuel A.

doi:10.1016/j.humpath.2008.11.007

Cited by 78 publications

(48 citation statements)

References 21 publications

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“…Although most commonly identified in the head and neck, mucoepidermoid carcinomas can occur in many sites of the body including breast, 15 lung, 16 skin, 17 and thymus 18 among others. Independent of the site of the tumor, mucoepidermoid carcinomas are composed of epidermoid, mucous and intermediate cells, and lack keratinization and in situ carcinoma of the overlying mucosal surface.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] Furthermore, Clauditz et al 8 demonstrated that the frequency of MAML2 rearrangement significantly decreased with increased tumor grade. Achcar et al 11 showed MAML2 rearrangement in 13 of 17 (77%) pulmonary mucoepidermoid carcinomas, including 10 (of 10) low-grade and 3 (of 7) high-grade pulmonary mucoepidermoid carcinomas, while other lung tumors including adenosquamous, squamous and primary lung adenocarcinomas did not harbor that translocation. As the t(11;19)(q21;p13) translocation is considered disease-defining for mucoepidermoid carcinoma, its significance in pulmonary mucoepidermoid carcinoma warrants further study.…”

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confidence: 99%

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Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma

et al. 2014

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Pulmonary mucoepidermoid carcinoma is an uncommon but distinctive manifestation of mucoepidermoid carcinoma. Pulmonary mucoepidermoid carcinoma occurs in adults and children and can cause diagnostic problems, especially in small biopsies. Few studies have characterized the histologic and immunophenotypic features of pulmonary mucoepidermoid carcinoma. t(11;19)(q21;p13) is considered disease-defining for mucoepidermoid carcinoma; its significance in pulmonary mucoepidermoid carcinoma warrants further study. Forty three pulmonary mucoepidermoid carcinomas were re-reviewed and graded according to the Brandwein grading system for mucoepidermoid carcinoma. Four cases were excluded because of a split opinion between pathology report and re-review. These cases were negative for MAML2 rearrangement by FISH. TTF-1, napsin A, p40 and p63 immunostains were scored: 0 (negative), 1 (1-25% tumor cells), 2 (26-50%), 3 (51-75%) or 4 (>75%). FISH to detect MAML2 rearrangement used a MAML2-11q21 break-apart probe. Thirty nine pulmonary mucoepidermoid carcinoma (4 low, 30 intermediate, 5 high grade) contained mucous, epidermoid and intermediate cells and lacked keratinization and in situ carcinoma of the overlying epithelium. All cases with available gross description (n=22) had a central/endo- or peribronchial location. All 25 cases tested for immunohistochemistry were positive (scores 1-4) for p63; 23 also expressed p40. In six cases, the p63 score was higher than p40. TTF-1 and napsin were uniformly negative in all 25 cases. MAML2 rearrangement was identified by FISH in each of the 24 cases tested (3 low, 19 intermediate, 2 high grade). Clinical history was available in 29 patients (15 men) (median age, 48 years) with follow-up in 24 (median, 8.4 years). Five patients died of unrelated causes; one developed metastatic pulmonary mucoepidermoid carcinoma. In conclusion, features helpful in distinguishing pulmonary mucoepidermoid carcinoma from other lung cancers include its central/endo- or peribronchial location together with the presence of mucous cells, p63 expression, lack of keratinization and MAML2 rearrangement. TTF-1 and napsin are typically not expressed.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma

et al. 2014

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“…MAML2 rearrangements occur in up to 75 % of MEC, but their detection is not site-specific. MAML2 rearrangements are found not just in MECs derived from the major salivary glands [23,24,31], but have been reported in MEC of the lung [32], uterine cervix [33], and thymus [34]. Indeed, 2 of 3 tested central MECs of the gnathic bones have been found to harbor MAML2 rearrangements [29,30].…”

Section: Discussionmentioning

confidence: 99%

Glandular Odontogenic Cysts (GOCs) Lack MAML2 Rearrangements: A Finding to Discredit the Putative Nature of GOC as a Precursor to Central Mucoepidermoid Carcinoma

Bishop

Yonescu

Batista

et al. 2014

Head and Neck Pathol

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Glandular odontogenic cyst (GOC) is a cyst of the gnathic bones that is characterized by squamous and glandular differentiation. The histopathologic features of GOC overlap considerably with central mucoepidermoid carcinoma (MEC), suggesting that GOC could be a precursor lesion to, or even a low-grade form of, central MEC. Differentiating the two lesions may be difficult or impossible on a limited biopsy. MAML2 rearrangements have been recently found to be specific for MEC, even those arising in the jaws. An analysis of MAML2 in GOCs could help clarify its relationship with central MEC. Tissue blocks from 21 GOCs and 5 central MECs were retrieved from the surgical pathology archives of The Johns Hopkins Hospital. Each MEC exhibited solid areas and clear-cut stromal invasion. In addition, 4 of the MECs demonstrated cystic areas that were histologically similar to GOC. Breakapart fluorescence in situ hybridization for MAML2 was performed. For the MECs, analysis was performed on both the solid components and the cystic areas that resembled GOC. MAML2 rearrangements were identified in all 5 of the MECs, but in none of the 21 GOCs (100 vs. 0 %; p \ 0.0001, Fisher's Exact). In the MECs, the rearrangement was present in both the solid and GOC-like cystic areas. While central MECs consistently harbor the MAML2 rearrangement, even in low-grade cystic areas that resemble a pre-existing GOC, true GOCs do not. Accordingly, GOC does not appear to represent an early or low-grade form of central MEC, but rather an unrelated lesion. The high sensitivity and specificity of MAML2 rearrangement for MECs points to its utility as a diagnostic adjunct in separating mucinous cystic lesions of the gnathic bones.

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“…The Crtc1-Maml2 fusion transcript was subsequently identified in primary thyroid, breast, cervix, lung and cutaneous sweat gland tumors with clear-cell, mucoepidermoid tumor-like histological features (Enlund et al, 2004;Behboudi et al, 2005;Kazakov et al, 2007;Tirado et al, 2007;Achcar et al, 2009;Camelo-Piragua et al, 2009;Kaye, 2009;Lennerz et al, 2009) unifying a group of tumors that arise from mucous/serous glands scattered throughout the body. As Crtc gene members are potent cAMP/CREB co-activators (Conkright et al, 2003;Iourgenko et al, 2003) and the ectopic expression of Crtc1-Maml2 activated a similar group of target genes (Coxon et al, 2005;Wu et al, 2005), a current model proposes that the fusion oncogene transforms cells by aberrantly co-activating specific Crtc1-inducible targets (Kaye, 2006).…”

Section: Introductionmentioning

confidence: 99%

Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer

et al. 2009

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Activation of Crtc1 (also known as Mect1/Torc1) by a t(11;19) chromosomal rearrangement underlies the etiology of malignant salivary gland tumors. As LKB1 is a target for mutational inactivation in lung cancer and was recently shown to regulate hepatic Crtc2/CREB transcriptional activity in mice, we now present evidence suggesting disruption of an LKB1/Crtc pathway in cancer. Although Crtc1 is preferentially expressed in adult brain tissues, we observed elevated levels of steadystate Crtc1 in thoracic tumors. In addition, we show that somatic loss of LKB1 is associated with underphosphorylation of endogenous Crtc1, enhanced Crtc1 nuclear localization and enhanced expression of the Crtc prototypic target gene, NR4A2/Nurr1. Inhibition of NR4A2 was associated with growth suppression of LKB1 null tumors, but showed little effect on LKB1-wildtype cells. These data strengthen the role of dysregulated Crtc as a bona fide cancer gene, present a new element to the complex LKB1 tumorigenic axis, and suggest that Crtc genes may be aberrantly activated in a wider range of common adult malignancies.

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Mammalian mastermind like 2 11q21 gene rearrangement in bronchopulmonary mucoepidermoid carcinoma

Cited by 78 publications

References 21 publications

Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma

Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma

Glandular Odontogenic Cysts (GOCs) Lack MAML2 Rearrangements: A Finding to Discredit the Putative Nature of GOC as a Precursor to Central Mucoepidermoid Carcinoma

Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer

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