Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luís; Hermsen, Mario

doi:10.1007/s13402-011-0037-5

Cited by 31 publications

(25 citation statements)

References 32 publications

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“…Consistent with this observation, a decreased cell population with myoepithelial differentiation has been consistently described in high-grade breast adenoid cystic carcinomas and transformed adenoid cystic carcinoma of the salivary glands. 17,54 …”

Section: Resultsmentioning

confidence: 99%

“…A loss at 6q23.3-6q27 was found in both components (Figure 3b), and this genomic locus is consistent with the regions previously described as recurrently lost in breast adenoid cystic carcinomas 7 and in salivary gland adenoid cystic carcinomas with high-grade transformation. 54 All components of AdCC2 displayed losses of chromosomes 4, 7, 14 and X (Figure 4b). The high-grade triple-negative breast cancer component of AdCC2 also harbored a subclonal gain of chromosome 21.…”

Section: Resultsmentioning

confidence: 99%

“…Several studies including small cohorts of patients with salivary gland adenoid cystic carcinomas 54,57,58 suggested that TP53 inactivation 17,54,57 and/ or amplification of 8q24.12-q24.13 encompassing MYC 57 may play a role in high-grade transformation of these lesions. Neither breast adenoid cystic carcinomas analyzed here harbored TP53 mutations and/ or MYC amplification.…”

Section: Discussionmentioning

confidence: 99%

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Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer

et al. 2016

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Adenoid cystic carcinoma of the breast is a rare histologic type of triple-negative breast cancer with an indolent clinical behavior, often driven by the MYB-NFIB fusion gene. Here we sought to define the repertoire of somatic genetic alterations in two adenoid cystic carcinomas associated with high-grade triple-negative breast cancer. The different components of each case were subjected to copy number profiling and massively parallel sequencing targeting all exons and selected regulatory and intronic regions of 488 genes. Reverse transcription PCR and fluorescence in situ hybridization were employed to investigate the presence of the MYB-NFIB translocation. The MYB-NFIB fusion gene was detected in both adenoid cystic carcinomas and their associated high-grade triple-negative breast cancer components. Whilst the distinct components of both cases displayed similar patterns of gene copy number alterations, massively parallel sequencing analysis revealed intra-tumor genetic heterogeneity. In case 1, progression from the trabecular adenoid cystic carcinoma to the high-grade triple-negative breast cancer was found to involve clonal shifts with enrichment of mutations affecting EP300, NOTCH1, ERBB2 and FGFR1 in the high-grade triple-negative breast cancer. In case 2, a clonal KMT2C mutation was present in the cribriform adenoid cystic carcinoma, solid adenoid cystic carcinoma and high-grade triple-negative breast cancer components, whereas a mutation affecting MYB was present only in the solid and high-grade triple-negative breast cancer areas and additional three mutations targeting STAG2, KDM6A and CDK12 were restricted to the high-grade triple-negative breast cancer. In conclusion, adenoid cystic carcinomas of the breast with high-grade transformation are underpinned by MYB-NFIB fusion gene, and, akin to other forms of cancer, may be constituted by a mosaic of cancer cell clones at diagnosis. The progression from adenoid cystic carcinoma to high-grade triple-negative breast cancer of no special type may involve the selection of neoplastic clones and/ or the acquisition of additional genetic alterations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer

et al. 2016

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“…A total of approximately 40 cases of AdCC with high grade transformation (AdCC-HGT) have been recognized in the literature to date [30–32]. AdCC-HGT is a highly aggressive tumor with a strong tendency to recur and metastasize to regional lymph nodes (57% in the review of Seethala et al [31]) and to distant organs.…”

Section: Incidence and Consequences Of Cervical Lymph Node Metastasismentioning

confidence: 99%

Cervical lymph node metastasis in adenoid cystic carcinoma of oral cavity and oropharynx: A collective international review

et al. 2016

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The purpose of this study was to establish general guidelines in the management of the N0 neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to improve the survival of these patients and/or reduce the risk of neck recurrences. The incidence of cervical node metastasis at diagnosis of head and neck AdCC is variable, and ranges between 3% and 16%. Metastasis to the cervical lymph nodes of intraoral and oropharyngeal AdCC varies from 2% to 43%, with the lower rates pertaining to palatal AdCC and the higher rates to base of the tongue. Neck node recurrence may happen after treatment in 0–14% of AdCC, is highly dependent on the extent of the treatment and is very rare in patients who have been treated with therapeutic or elective neck dissections, or elective neck irradiation. Lymph node involvement with or without extracapsular extension in AdCC has been shown in most reports to be independently associated with decreased overall and cause-specific survival, probably because lymph node involvement is a risk factor for subsequent distant metastasis. The overall rate of occult neck metastasis in patients with head and neck AdCC ranges from 15% to 44%, but occult neck metastasis from oral cavity and/or oropharynx seems to occur more frequently than from other locations such as the sinonasal tract and major salivary glands. Nevertheless, the benefit of elective neck dissection (END) in AdCC is not comparable to that of squamous cell carcinoma, because the main cause of failure is not related to neck or local recurrence, but rather, to distant failure. Therefore, END should be considered in patients with a cN0 neck with AdCC in some high risk oral and oropharyngeal locations when postoperative RT is not planned, or the rare AdCC-high grade transformation.

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“…A high-resolution microarray comparative genomic hybridization (CGH) analysis revealed a correlation between the number of chromosomal aberrations and the degree of gland differentiation of the transformed component [60]. FISH analyses have demonstrated increases in MYC and low-level increases in ERBB2 , formerly known as HER2/neu , in cases showing gains on array CGH in these regions [61].…”

Section: Introductionmentioning

confidence: 99%

“Dedifferentiation” and High-Grade Transformation in Salivary Gland Carcinomas

Nagao

2013

Head and Neck Pathol

130

126

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“Dedifferentiation” and/or high-grade transformation (HGT) has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, myoepithelial carcinoma, low-grade mucoepidermoid carcinoma and hyalinizing clear cell carcinoma, although the phenomenon is a rare event. Recent authors tend to preferably use the term HGT instead of “dedifferentiation” in these cases. HGT-tumors are composed of conventional carcinomas juxtaposed with areas of HG morphology, usually either poorly differentiated adenocarcinoma or “undifferentiated” carcinoma, in which the original line of differentiation is no longer evident. The HG component is generally composed of solid nests, sometimes occurring in cribriform pattern of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli and abundant cytoplasm. Frequent mitoses and extensive necrosis is evident. The Ki-67 labeling index is consistently higher in the HG component. p53 abnormalities have been demonstrated in the transformed component in a few examples, but the frequency varies by the histologic type. HER-2/neu overexpression and/or gene amplification is considerably exceptional. The molecular-genetic mechanisms responsible for the pathway of HGT in salivary gland carcinomas largely still remain to be elucidated. Salivary gland carcinomas with HGT have been shown to be more aggressive than conventional carcinomas with a poorer prognosis, accompanied by higher local recurrence rate and propensity for cervical lymph node metastasis, suggesting the need for wider resection and neck dissection.

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Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

Cited by 31 publications

References 32 publications

Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer

Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer

Cervical lymph node metastasis in adenoid cystic carcinoma of oral cavity and oropharynx: A collective international review

“Dedifferentiation” and High-Grade Transformation in Salivary Gland Carcinomas

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