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17 pages, 642 KiB

Open AccessArticle

Phase Angle in Head and Neck Cancer: A Sex-Differential Analysis from Biological and Clinical Behavior to Health-Related Quality of Life

by Brenda-Eugenia Martínez-Herrera, Leonardo-Xicotencatl Gutiérrez-Rodríguez, Benjamín Trujillo-Hernández, Michelle-Guadalupe Muñoz-García, Luz-María Cervantes-González, Laura-Liliana José Ochoa, Javier-Andrés González-Rodríguez, Alejandro Solórzano-Meléndez, Eduardo Gómez-Sánchez, Gabriela-Guadalupe Carrillo-Nuñez, Mario Salazar-Páramo, Arnulfo-Hernán Nava-Zavala, Martha-Cecilia Velázquez-Flores, Carlos-M. Nuño-Guzmán, Mario-Alberto Mireles-Ramírez, Luz-Ma.-Adriana Balderas-Peña and Daniel Sat-Muñoz

Biomedicines 2023, 11(6), 1696; https://doi.org/10.3390/biomedicines11061696 - 12 Jun 2023

Cited by 2 | Viewed by 1828

Abstract

Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the [...] Read more.

Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the phase angle (PA) differs across sex as a predictor of poor prognosis, low quality-of-life (QoL) scores, and mortality in patients with head and neck cancer. This follow-up study presents a sex-differential analysis in a prospective cohort of 139 head and neck cancer patients categorized by sex as male (n = 107) and female (n = 32). Patients were compared in terms of nutritional, biochemical, and quality-of-life indicators between low and normal PA in women (<3.9° (n = 14, 43.75%) and ≥3.9°) and men (<4.5° (n = 62, 57.9%) and ≥4.5°). Our results show that most patients were in locally advanced clinical stages (women: n = 21 (65.7%); men: n = 67 (62.6%)) and that patients with low PA had a lower punctuation in parameters such as handgrip strength, four-meter walking speed, albumin, C-reactive protein (CRP), and CRP/albumin ratio (CAR), as well as the worst QoL scores in functional and symptomatic scales in both the male and female groups. A comparison between sexes revealed significant disparities; malnourishment and tumor cachexia related to an inflammatory state was more evident in the women’s group. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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9 pages, 791 KiB

Open AccessArticle

Which Epidemiological Characteristics Drive Decision Making in the Management of Patients with Vestibular Schwannoma?

by Zdeněk Fík, Aleš Vlasák, Eduard Zvěřina, Jaroslav Sýba, Jan Lazák, Lenka Peterková, Vladimír Koucký and Jan Betka

Biomedicines 2023, 11(2), 340; https://doi.org/10.3390/biomedicines11020340 - 25 Jan 2023

Cited by 1 | Viewed by 1186

Abstract

The incidence of sporadic vestibular schwannoma has significantly increased over the past few decades. However, there is no method currently available to accurately predict the risk of subsequent tumor growth. The difference in the management of five patient groups has been evaluated: wait [...] Read more.

The incidence of sporadic vestibular schwannoma has significantly increased over the past few decades. However, there is no method currently available to accurately predict the risk of subsequent tumor growth. The difference in the management of five patient groups has been evaluated: wait and scan, conversion to microsurgery, conversion to stereoradiotherapy, sterioradiotherapy, and microsurgery. In total, 463 patients with vestibular schwannoma have been consulted in our department from 2010 through 2016. Of the 250 patients initially indicated for observation, 32.4% were later indicated for active treatment. Younger patients were more frequently indicated for surgery (mean age 48 years) compared to older patients, who were more often indicated for stereoradiotherapy (mean age 62 years). Tumor growth was observed more often in patients under 60 years of age and in patients with tumors greater than 10 mm. In elderly patients, including those with larger tumors, a conservative approach is the optimal solution. If tumor growth occurs in the wait-and-scan strategy, it is still possible to continue with a conservative approach in some situations. The duration of follow-up scans is still a matter of debate, as tumors can begin to grow after 5 years from the initial diagnosis. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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17 pages, 1835 KiB

Open AccessArticle

Clinicopathological Profile of Medullary Thyroid Carcinoma—Could We Predict Aggressive Behavior?

by Simona Eliza Giusca, Elena Corina Andriescu, Irina Draga Caruntu and Delia Ciobanu

Biomedicines 2023, 11(1), 116; https://doi.org/10.3390/biomedicines11010116 - 3 Jan 2023

Cited by 1 | Viewed by 2468

Abstract

Medullary thyroid carcinoma (MTC) accounts for only 2–5% of all thyroid malignancies. Clinical and pathological characteristics alone may suffice to predict outcomes, but unstable behavior in some cases suggests that other factors may influence a worse course of the disease. This study aims [...] Read more.

Medullary thyroid carcinoma (MTC) accounts for only 2–5% of all thyroid malignancies. Clinical and pathological characteristics alone may suffice to predict outcomes, but unstable behavior in some cases suggests that other factors may influence a worse course of the disease. This study aims to identify criteria that could predict increased aggressiveness. We analyzed 59 consecutive MTC cases. We focused on the relationships among clinicopathological characteristics, parameters of aggressiveness (extrathyroidal extension, lymphovascular invasion, and lymph node metastasis), and parameters for MTC grading. Statistically significant correlations were found for tumor size, lymphovascular invasion, and lymph node metastasis and tumor focality and lymph node metastasis. Our results showed, in tumors larger than 40 mm, odds ratios (ODs) of 13.695 and 6 for lymphovascular invasion and lymph node metastasis, respectively; in multifocal tumors, we registered an OD of 9.42 for lymph node metastasis. No significant correlation was found for the parameters of the MTC grading system when assessed individually and integrated by reporting low-grade and high-grade risk groups. Although our data indicate that lymphovascular invasion and lymph node metastasis remain significant markers for aggressiveness, studies on larger series of cases are mandatory to detect and validate new factors responsible for the variable course of MTC. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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16 pages, 2863 KiB

Open AccessArticle

A Treatment Decision Support Model for Laryngeal Cancer Based on Bayesian Networks

by Aisha Hikal, Jan Gaebel, Thomas Neumuth, Andreas Dietz and Matthaeus Stoehr

Biomedicines 2023, 11(1), 110; https://doi.org/10.3390/biomedicines11010110 - 1 Jan 2023

Cited by 5 | Viewed by 1769

Abstract

The increase in diagnostic and therapeutic procedures in the treatment of oncological diseases, as well as the limited capacity of experts to provide information, necessitates the development of therapy decision support systems (TDSS). We have developed a treatment decision model that integrates available [...] Read more.

The increase in diagnostic and therapeutic procedures in the treatment of oncological diseases, as well as the limited capacity of experts to provide information, necessitates the development of therapy decision support systems (TDSS). We have developed a treatment decision model that integrates available patient information as well as tumor characteristics. They are assessed according to their relevance in evaluating the optimal therapy option. Our treatment model is based on Bayesian networks (BN) which integrate patient-specific data with expert-based implemented causalities to suggest the optimal therapy option and therefore potentially support the decision-making process for treatment of laryngeal carcinoma. To test the reliability of our model, we compared the calculations of our model with the documented therapy from our data set, which contained information on 97 patients with laryngeal carcinoma. Information on 92 patients was used in our analyses and the model suggested the correct treatment in 419 out of 460 treatment modalities (accuracy of 91%). However, unequally distributed clinical data in the test sets revealed weak spots in the model that require revision for future utilization. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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12 pages, 606 KiB

Open AccessArticle

Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer

by Irena Ivković, Zgjim Limani, Antonia Jakovčević, Srećko Gajović, Sven Seiwerth, Ana Đanić Hadžibegović and Drago Prgomet

Biomedicines 2023, 11(1), 53; https://doi.org/10.3390/biomedicines11010053 - 26 Dec 2022

Cited by 2 | Viewed by 1722

Abstract

The early-stage diagnosis of papillary thyroid cancer (PTC) has significantly increased in incidence worldwide without any beneficial impact on survival. In order to improve the risk assessment in PTC, we have conducted a retrospective study in which we analyzed the BRAF V600E mutation [...] Read more.

The early-stage diagnosis of papillary thyroid cancer (PTC) has significantly increased in incidence worldwide without any beneficial impact on survival. In order to improve the risk assessment in PTC, we have conducted a retrospective study in which we analyzed the BRAF V600E mutation and CPSF2 protein expression as prognostic markers on archival tissue samples of 49 patients without (control group) and 97 patients with (study group) PTC metastases in the cervical lymph nodes at the time of initial diagnosis. Our aim was to correlate the BRAF V600E mutation and the expression of CPSF2 protein with the clinical and pathological features of PTC. The expression of CPSF2 protein was evaluated via immunohistochemistry and graded semi-quantitatively. The presence of the BRAF V600E mutation was determined via real-time polymerase chain reac-tion (PCR). CPSF2 protein < 3+ intensity expression was correlated with more frequent recurrences (Fisher-Freeman-Halton exact test; p = 0.010; 95% CI: 1.26–22.03), and patients who presented with the BRAF V600E mutation and CPSF2 protein expression < 3+ intensity had shorter disease-free survival (log-rank test; 105.0 months vs. 146.6 months; p < 0.001; HR 8.32, 95% CI: 2.91–23.83), whereas patients with PTC who had CPSF2 expression 3+ had longer disease-free survival in correlation with other lower intensity expressions of CPSF2 protein (log-rank test; 139.7 months vs. 129.6 months; p = 0.008). The multivariate analysis showed that younger patients with CPSF2 protein expression <3+ and the BRAF V600E mutation are at an increased risk for recurrence and require more intensive monitoring (Cox proportional hazards regression model; X2 = 17.5, df = 10, p = 0.025). Our results correlate the BRAF V600E mutation and CPSF2 protein expression with recurrence and disease-free survival as relevant prognostic factors for PTC. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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12 pages, 911 KiB

Open AccessArticle

Epidemiological, Clinical, and Genomic Profile in Head and Neck Cancer Patients and Their Families

by Thiago Celestino Chulam, Fernanda Bernardi Bertonha, Rolando André Rios Villacis, João Gonçalves Filho, Luiz Paulo Kowalski and Silvia Regina Rogatto

Biomedicines 2022, 10(12), 3278; https://doi.org/10.3390/biomedicines10123278 - 17 Dec 2022

Cited by 2 | Viewed by 1995

Abstract

Inherited cancer predisposition genes are described as risk factors in head and neck cancer (HNC) families. To explore the clinical and epidemiological data and their association with a family history of cancer, we recruited 74 patients and 164 relatives affected by cancer. The [...] Read more.

Inherited cancer predisposition genes are described as risk factors in head and neck cancer (HNC) families. To explore the clinical and epidemiological data and their association with a family history of cancer, we recruited 74 patients and 164 relatives affected by cancer. The germline copy number alterations were evaluated in 18 patients using array comparative genomic hybridization. Two or more first-degree relatives with HNC, tobacco-associated tumor sites (lung, esophagus, and pancreas), or other related tumors (breast, colon, kidney, bladder, cervix, stomach carcinomas, and melanoma) were reported in 74 families. Ten index patients had no exposure to any known risk factors. Family members presented tumors of 19 topographies (30 head and neck, 26 breast, 21 colon). In first-degree relatives, siblings were frequently affected by cancer (n = 58, 13 had HNC). Breast cancer (n = 21), HNC (n = 19), and uterine carcinoma (n = 15) were commonly found in first-degree relatives and HNC in second-degree relatives (n = 11). Nineteen germline genomic imbalances were detected in 13 patients; three presented gains of WRD genes. The number of HNC patients, the degree of kinship, and the tumor types detected in each relative support the role of heredity in these families. Germline alterations may potentially contribute to cancer development. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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15 pages, 2622 KiB

Open AccessArticle

Comparing TIMP-1 and Hsp70 in Blood and Saliva as Potential Prognostic Markers in HNSCC

by Jakob Rinecker, Romina Roesch, Sara Krippgans, Markus Nieberler, Leonhard Stark, Stefan Stangl, Bernhard Haller, Kristin Fritsche, Gabriele Multhoff, Andreas Knopf, Christof Winter, Barbara Wollenberg and Markus Wirth

Biomedicines 2022, 10(12), 3225; https://doi.org/10.3390/biomedicines10123225 - 12 Dec 2022

Cited by 2 | Viewed by 1491

Abstract

(1) Background: Currently, there is no clinically used liquid biomarker in head and neck squamous cell carcinoma (HNSCC) patients. One reason could be the limited shedding of tumor material in early disease stages. Molecular diagnostics assessing both blood and especially saliva could potentially [...] Read more.

(1) Background: Currently, there is no clinically used liquid biomarker in head and neck squamous cell carcinoma (HNSCC) patients. One reason could be the limited shedding of tumor material in early disease stages. Molecular diagnostics assessing both blood and especially saliva could potentially improve the accuracy of biomarkers. In this prospective study, two markers, tissue inhibitor of metalloprotease-1 (TIMP-1) and heat shock protein 70 (Hsp70), were analyzed in HNSCC patients. The purpose of the study was to evaluate differences between saliva and serum as sample material. Further, their prognostic and predictive value and usefulness for early detection was assessed. (2) Methods: A total of 73 HNSCC patients were prospectively monitored by collecting blood and saliva before, during, and after therapy, as well as in the follow-up period between 2018 and 2021. In total, 212 serum and 194 saliva samples were collected. A control group consisting of 40 subjects (15 patients with local infections in the head and neck area and 25 without infections) were examined as well. The collected samples were evaluated for the two proteins by using an enzyme-linked immunosorbent assay (ELISA). (3) RESULTS: The TIMP-1 concentration correlated significantly in blood and saliva, whereas the Hsp70 concentration did not. Saliva TIMP-1 was significantly higher in tumor patients compared to the control group (p = 0.013). High pretreatment TIMP-1 saliva levels were associated with significantly poorer disease-free survival (DFS) (p = 0.02). A high saliva TIMP-1/Hsp70 ratio was significantly associated with poorer DFS (HR: 1.4; 95% CI: 1.04–1.88; p = 0.026) and a high TIMP-1 serum concentration was significantly associated with poorer PFS (HR: 1.9; 95% CI: 1.2, 2.8; p = 0.003) and poorer overall survival (OS) (HR: 2.9; 95% CI: 1.4, 5.9; p = 0.003) in the Cox proportional hazards model. The saliva TIMP-1 to Hsp70 ratio was significantly higher at the time of recurrence (p = 0.015). Conclusion: TIMP-1 in serum is a promising prognostic marker for HNSCC. Saliva TIMP-1 and the saliva TIMP-1 to Hsp70 ratio provides additional information on the disease-free survival. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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11 pages, 639 KiB

Open AccessArticle

Role of Matrix Metalloproteinases and Their Inhibitors in Locally Invasive Papillary Thyroid Cancer

by Irena Ivković, Zgjim Limani, Antonia Jakovčević, Dražen Huić and Drago Prgomet

Biomedicines 2022, 10(12), 3178; https://doi.org/10.3390/biomedicines10123178 - 8 Dec 2022

Cited by 9 | Viewed by 1700

Abstract

Locally invasive papillary thyroid carcinoma (PTC) protrudes beyond the thyroid capsule and invades local structures. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in local invasion and metastasis in PTC. The aim of our study was to determine expression levels of MMP-1, [...] Read more.

Locally invasive papillary thyroid carcinoma (PTC) protrudes beyond the thyroid capsule and invades local structures. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are implicated in local invasion and metastasis in PTC. The aim of our study was to determine expression levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in tissue specimens of invasive and non-invasive PTC. Our hypothesis was that expression levels of these biomarkers correlate with the development of locally invasive PTC. In our single-center study we retrospectively investigated MMP and TIMP expression levels in 50 samples of thyroid tissue diagnosed as locally invasive papillary carcinoma (study group) and 30 samples of thyroid tissue diagnosed as non-invasive, non-metastatic papillary carcinoma (control group). Tissue specimens were immunohistochemically stained with primary monoclonal antibodies against MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2. When correlating expression levels of MMPs and TIMPs in thyroid tissue, statistically significant differences were found for MMP-1 and TIMP-1 expression (p < 0.001; Mann–Whitney U test) with the highest levels of expression in the invasive PTC group. Although expression of MMP-9 and TIMP-2 was higher in invasive PTC, the differences were not statistically significant. Elevated expression of MMP-1 and TIMP-1 in tumor tissue can predict invasiveness for PTC. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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11 pages, 437 KiB

Open AccessArticle

Effect of Oral Exercise on Trismus after Oral Cancer Radiotherapy: A Quasi-Experimental Study

by Tsae-Jyy Wang, Kuo-Feng Wu, Hung-Ming Wang, Shu-Yuan Liang, Ting-Ru Lin and Yi-Wei Chen

Biomedicines 2022, 10(11), 2951; https://doi.org/10.3390/biomedicines10112951 - 17 Nov 2022

Cited by 5 | Viewed by 2188

Abstract

Trismus is a severe complication of oral cancer treatment. Oral exercise is a potentially helpful approach for preventing or improving trismus. The study aimed to test the efficacy of an oral exercise for enhancing the maximum inter-incisal opening (MIO) in patients undergoing surgery [...] Read more.

Trismus is a severe complication of oral cancer treatment. Oral exercise is a potentially helpful approach for preventing or improving trismus. The study aimed to test the efficacy of an oral exercise for enhancing the maximum inter-incisal opening (MIO) in patients undergoing surgery and radiotherapy for oral cancer. This is a quasi-experimental study. A sample of 69 oral cancer patients completed the study, with 35 in the control group and 34 in the intervention group. Intervention subjects were asked to perform three 20-min oral exercise sessions per day for six months. Data on oral exercise practicing time, MIO, and mandibular function impairment were collected at the last radiotherapy exposure (T1), three months (T2), and six months (T3) after the radiotherapy. At T3, the intervention group exercised 217.1 min (95%CI: 107.4~326.7) more than the control group. The generalized estimation equations showed a statistically significant group-by-time interaction in MIO. The change in MIO score from T1 to T3, as indicated by the regression slope, was 2.5 mm (95%CI: 0.4~4.6) greater in the intervention group than in the control group. The results support the efficacy of the study intervention for improving patient exercise adherence and MIO. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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14 pages, 3177 KiB

Open AccessArticle

PTC124 Rescues Nonsense Mutation of Two Tumor Suppressor Genes NOTCH1 and FAT1 to Repress HNSCC Cell Proliferation

by Ming-Han Wu, Rui-Yu Lu, Si-Jie Yu, Yi-Zhen Tsai, Ying-Chen Lin, Zhi-Yu Bai, Ruo-Yu Liao, Yi-Chiang Hsu, Chia-Chi Chen and Bi-He Cai

Biomedicines 2022, 10(11), 2948; https://doi.org/10.3390/biomedicines10112948 - 16 Nov 2022

Cited by 5 | Viewed by 2349

Abstract

(1) Background: PTC124 (Ataluren) is an investigational drug for the treatment of nonsense mutation-mediated genetic diseases. With the exception of the TP53 tumor suppressor gene, there has been little research on cancers with nonsense mutation. By conducting a database search, we found that [...] Read more.

(1) Background: PTC124 (Ataluren) is an investigational drug for the treatment of nonsense mutation-mediated genetic diseases. With the exception of the TP53 tumor suppressor gene, there has been little research on cancers with nonsense mutation. By conducting a database search, we found that another two tumor suppressor genes, NOTCH1 and FAT1, have a high nonsense mutation rate in head and neck squamous cell carcinoma (HNSCC). PTC124 may re-express the functional NOTCH1 or FAT1 in nonsense mutation NOTCH1 or FAT1 in HSNCC (2) Methods: DOK (with NOTCH1 Y550X) or HO-1-u-1 (with FAT1 E378X) HNSCC cells were treated with PTC124, and the NOTCH1 or FAT1 expression, cell viability, and NOTCH1- or FAT1-related downstream gene profiles were assayed. (3) Results: PTC124 was able to induce NOTCH1 or FAT1 expression in DOK and HO-1-u-1 cells. PTC124 was able to upregulate NOTCH downstream genes HES5, AJUBA, and ADAM10 in DOK cells. PTC124 enhanced DDIT4, which is under the control of the FAT1–YAP1 pathway, in HO-1-u-1 cells. FLI-06 (a NOTCH signaling inhibitor) reversed PTC124-mediated cell growth inhibition in DOK cells. PTC124 could reverse TT-10 (a YAP signaling activator)-mediated HO-1-u-1 cell proliferation. (4) Conclusions: PTC124 can rescue nonsense mutation of NOTCH1 and FAT1 to repress HNSCC cell proliferation. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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Review

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13 pages, 605 KiB

Open AccessReview

Radiomics in Hypopharyngeal Cancer Management: A State-of-the-Art Review

by Carlos M. Chiesa-Estomba, Miguel Mayo-Yanez, Orlando Guntinas-Lichius, Vincent Vander-Poorten, Robert P. Takes, Remco de Bree, Gyorgy B. Halmos, Nabil F. Saba, Sandra Nuyts and Alfio Ferlito

Biomedicines 2023, 11(3), 805; https://doi.org/10.3390/biomedicines11030805 - 6 Mar 2023

Viewed by 2149

Abstract

(1) Background: Hypopharyngeal squamous cell carcinomas usually present with locally advanced disease and a correspondingly poor prognosis. Currently, efforts are being made to improve tumor characterization and provide insightful information for outcome prediction. Radiomics is an emerging area of study that involves the [...] Read more.

(1) Background: Hypopharyngeal squamous cell carcinomas usually present with locally advanced disease and a correspondingly poor prognosis. Currently, efforts are being made to improve tumor characterization and provide insightful information for outcome prediction. Radiomics is an emerging area of study that involves the conversion of medical images into mineable data; these data are then used to extract quantitative features based on shape, intensity, texture, and other parameters; (2) Methods: A systematic review of the peer-reviewed literature was conducted; (3) Results: A total of 437 manuscripts were identified. Fifteen manuscripts met the inclusion criteria. The main targets described were the evaluation of textural features to determine tumor-programmed death-ligand 1 expression; a surrogate for microvessel density and heterogeneity of perfusion; patient stratification into groups at high and low risk of progression; prediction of early recurrence, 1-year locoregional failure and survival outcome, including progression-free survival and overall survival, in patients with locally advanced HPSCC; thyroid cartilage invasion, early disease progression, recurrence, induction chemotherapy response, treatment response, and prognosis; and (4) Conclusions: our findings suggest that radiomics represents a potentially useful tool in the diagnostic workup as well as during the treatment and follow-up of patients with HPSCC. Large prospective studies are essential to validate this technology in these patients. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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24 pages, 2362 KiB

Open AccessReview

Tumor Biology and Microenvironment of Vestibular Schwannoma-Relation to Tumor Growth and Hearing Loss

by Michaela Tesařová, Lenka Peterková, Monika Šťastná, Michal Kolář, Lukáš Lacina, Karel Smetana, Jr., Radovan Hynek, Jan Betka, Aleš Vlasák, Petr Lukeš and Zdeněk Fík

Biomedicines 2023, 11(1), 32; https://doi.org/10.3390/biomedicines11010032 - 23 Dec 2022

Cited by 5 | Viewed by 2850

Abstract

Vestibular schwannoma is the most common benign neoplasm of the cerebellopontine angle. It arises from Schwann cells of the vestibular nerve. The first symptoms of vestibular schwannoma include hearing loss, tinnitus, and vestibular symptoms. In the event of further growth, cerebellar and brainstem [...] Read more.

Vestibular schwannoma is the most common benign neoplasm of the cerebellopontine angle. It arises from Schwann cells of the vestibular nerve. The first symptoms of vestibular schwannoma include hearing loss, tinnitus, and vestibular symptoms. In the event of further growth, cerebellar and brainstem symptoms, along with palsy of the adjacent cranial nerves, may be present. Although hearing impairment is present in 95% of patients diagnosed with vestibular schwannoma, most tumors do not progress in size or have low growth rates. However, the clinical picture has unpredictable dynamics, and there are currently no reliable predictors of the tumor’s behavior. The etiology of the hearing loss in patients with vestibular schwannoma is unclear. Given the presence of hearing loss in patients with non-growing tumors, a purely mechanistic approach is insufficient. A possible explanation for this may be that the function of the auditory system may be affected by the paracrine activity of the tumor. Moreover, initiation of the development and growth progression of vestibular schwannomas is not yet clearly understood. Biallelic loss of the NF2 gene does not explain the occurrence in all patients; therefore, detection of gene expression abnormalities in cases of progressive growth is required. As in other areas of cancer research, the tumor microenvironment is coming to the forefront, also in vestibular schwannomas. In the paradigm of the tumor microenvironment, the stroma of the tumor actively influences the tumor’s behavior. However, research in the area of vestibular schwannomas is at an early stage. Thus, knowledge of the molecular mechanisms of tumorigenesis and interactions between cells present within the tumor is crucial for the diagnosis, prediction of tumor behavior, and targeted therapeutic interventions. In this review, we provide an overview of the current knowledge in the field of molecular biology and tumor microenvironment of vestibular schwannomas, as well as their relationship to tumor growth and hearing loss. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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13 pages, 1199 KiB

Open AccessReview

Chromosome Translocations, Gene Fusions, and Their Molecular Consequences in Pleomorphic Salivary Gland Adenomas

by Göran Stenman, Andre Fehr, Alena Skálová, Vincent Vander Poorten, Henrik Hellquist, Lauge Hjorth Mikkelsen, Nabil F. Saba, Orlando Guntinas-Lichius, Carlos Miguel Chiesa-Estomba, Mattias K. Andersson and Alfio Ferlito

Biomedicines 2022, 10(8), 1970; https://doi.org/10.3390/biomedicines10081970 - 14 Aug 2022

Cited by 14 | Viewed by 4122

Abstract

Salivary gland tumors are a heterogeneous group of tumors originating from the major and minor salivary glands. The pleomorphic adenoma (PA), which is the most common subtype, is a benign lesion showing a remarkable morphologic diversity and that, upon recurrence or malignant transformation, [...] Read more.

Salivary gland tumors are a heterogeneous group of tumors originating from the major and minor salivary glands. The pleomorphic adenoma (PA), which is the most common subtype, is a benign lesion showing a remarkable morphologic diversity and that, upon recurrence or malignant transformation, can cause significant clinical problems. Cytogenetic studies of >500 PAs have revealed a complex and recurrent pattern of chromosome rearrangements. In this review, we discuss the specificity and frequency of these rearrangements and their molecular/clinical consequences. The genomic hallmark of PA is translocations with breakpoints in 8q12 and 12q13-15 resulting in gene fusions involving the transcription factor genes PLAG1 and HMGA2. Until recently, the association between these two oncogenic drivers was obscure. Studies of the Silver–Russel syndrome, a growth retardation condition infrequently caused by mutations in IGF2/HMGA2/PLAG1, have provided new clues to the understanding of the molecular pathogenesis of PA. These studies have demonstrated that HMGA2 is an upstream regulator of PLAG1 and that HMGA2 regulates the expression of IGF2 via PLAG1. This provides a novel explanation for the 8q12/12q13-15 aberrations in PA and identifies IGF2 as a major oncogenic driver and therapeutic target in PA. These studies have important diagnostic and therapeutic implications for patients with PA. Full article

(This article belongs to the Special Issue Head and Neck Tumors 2.0)

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