Katri Aro

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

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. High-resolution 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=0.002). Twelve of 18 fusion-positive tumors had normal genomic profiles whereas only 1 out of 10 fusion-negative 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; P<0.0001). 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.

Saliva diagnostics – Current views and directions

In this review, we provide an update on the current and future applications of saliva for diagnostic purposes. There are many advantages of using saliva as a biofluid. Its collection is fast, easy, inexpensive, and non-invasive. In addition, saliva, as a “mirror of the body,” can reflect the physiological and pathological state of the body. Therefore, it serves as a diagnostic and monitoring tool in many fields of science such as medicine, dentistry, and pharmacotherapy. Introduced in 2008, the term “Salivaomics” aimed to highlight the rapid development of knowledge about various “omics” constituents of saliva, including: proteome, transcriptome, micro-RNA, metabolome, and microbiome. In the last few years, researchers have developed new technologies and validated a wide range of salivary biomarkers that will soon make the use of saliva a clinical reality. However, a great need still exists for convenient and accurate point-of-care devices that can serve as a non-invasive diagnostic tool. In addition, there is an urgent need to decipher the scientific rationale and mechanisms that convey systemic diseases to saliva. Another promising technology called liquid biopsy enables detection of circulating tumor cells (CTCs) and fragments of tumor DNA in saliva, thus enabling non-invasive early detection of various cancers. The newly developed technology—electric field-induced release and measurement (EFIRM) provides near perfect detection of actionable mutations in lung cancer patients. These recent advances widened the salivary diagnostic approach from the oral cavity to the whole physiological system, and thus point towards a promising future of salivary diagnostics for personalized individual medicine applications including clinical decisions and post-treatment outcome predictions. Impact statement The purpose of this mini-review is to make an update about the present and future applications of saliva as a diagnostic biofluid in many fields of science such as dentistry, medicine and pharmacotherapy. Using saliva as a fluid for diagnostic purposes would be a huge breakthrough for both patients and healthcare providers since saliva collection is easy, non-invasive and inexpensive. We will go through the current main diagnostic applications of saliva, and provide a highlight on the emerging, newly developing technologies and tools for cancer screening, detection and monitoring.

Saliva Liquid Biopsy for Point-of-Care Applications

Saliva is a non-invasive biofluid, which is easy to collect, transport, and store. Because of its accessibility and connection to systemic diseases, saliva is one of the best candidates for the advancement of point-of-care medicine, where individuals are able to easily monitor their health status by using portable convenient tools such as smartphones. There are a variety of scenarios with which saliva can be used: studies have been conducted on using saliva to measure stress hormones, enzyme levels, developmental disease biomarkers, and even cancer mutations. If validated biomarkers were combined with high-quality detection tools, saliva would open up a new frontier in high-quality healthcare, allowing physicians and patients to work together for real-time health monitoring and high-impact personalized preventative medicine. One of the most exciting emerging frontiers of saliva is liquid biopsy, which is a non-invasive means to assess the presence and characteristics of cancer in a patient. This article will review current basic knowledge of biomarkers, review their relation to different diseases and conditions, and explore liquid biopsy for point-of-care applications.

Preoperative evaluation and surgical planning of submandibular gland tumors: Submandibular gland tumors

Roughly half of submandibular gland neoplasms are malignant. Because preoperative information on the nature of these tumors remains limited, both preoperative evaluation and assessment of the extent of primary surgery warrant guidelines that are more accurate.

Complications after surgery for benign parotid gland neoplasms: A prospective cohort study

Prospective studies on procedure‐specific incidences of complications after benign parotid surgery are lacking. Predictive factors for postoperative facial dysfunction remain controversial.

Management of salivary gland malignancies in the pediatric population.

Purpose of reviewThe management of pediatric salivary gland cancer (SGC) remains a challenge, and long-term outcome data are lacking for these rare tumors. The heterogeneity of histopathological features in 24 different SGCs further complicates unequivocal treatment recommendations across different age groups. This review aims to outline the management guidelines for pediatric SGC. Recent findingsCompared with adults, pediatric SGC is more often localized to the primary site and of low-grade histology. Surgery remains the treatment of choice accompanied by oncological treatment in selected patients. Elective neck dissection seems unnecessary as the occurrence of occult metastases is rare. SummaryThis review provides information for clinicians to manage pediatric SGC highlighting the need for individually based treatment decisions at multidisciplinary head and neck centers.

Submandibular gland cancer: Specific features and treatment considerations

In the absence of unified treatment protocol, we evaluated the management and outcomes of submandibular gland cancers in an unselected patient series.

Sacrifice and extracranial reconstruction of the common or internal carotid artery in advanced head and neck carcinoma: Review and meta-analysis

Sacrifice and reconstruction of the carotid artery in cases of head and neck carcinoma with invasion of the common or internal carotid artery is debated.

Expression of hormone receptors in oropharyngeal squamous cell carcinoma

ObjectivesHormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer.Materials and methodsThis study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics.ResultsAR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival.ConclusionAR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.

Accuracy of preoperative MRI to assess lateral neck metastases in papillary thyroid carcinoma

Primary treatment of papillary thyroid carcinoma (PTC) with lateral lymph node metastasis is surgery, but the extent of lateral neck dissection remains undefined. Preoperative imaging is used to guide the extent of surgery, although its sensitivity and specificity for defining the number and level of affected lymph nodes on the lateral neck is relatively modest. Our aim was to assess the role of preoperative magnetic resonance imaging (MRI) in predicting the requisite levels of neck dissection in patients with regionally metastatic PTC, with a focus on Levels II and V. All patients with PTC and lateral neck metastasis who had undergone neck dissection at the Department of Otorhinolaryngology—Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland from 2013 to 2016 and had a preoperative MRI available were retrospectively reviewed. A head and neck radiologist re-evaluated all MRIs, and the imaging findings were compared with histopathology after neck dissection. In the cohort of 39 patients, preoperative MRI showed concordance with histopathology for Levels II and V as follows: sensitivity of 94 and 67%, specificity of 20 and 91%, positive predictive value of 56 and 75%, and negative predictive value of 75 and 87%, respectively. In PTC, MRI demonstrated fairly high specificity and negative predictive value for Level V metastasis, and future studies are needed to verify our results to omit prophylactic dissection of this level. Routine dissection of Level II in patients with regionally metastatic PTC needs to be considered, as MRI showed low specificity.