Molecular profile of tongue cancer in an 18-year-old female patient with no recognizable risk factor

BACKGROUND : The occurrence of oral tongue squamous cell carcinoma (TSCC) in nonsmoking young adults, especially females, has increased. Yet, there is no clear evidence to support the existence of any single determinant. This case reports the presence of TSCC in an 18-year-old female with no recognizable risk factor for oral cancer development. METHODS : Histological examination and p16 immunohistochemistry were performed. Formalin-fixed paraffin-embedded sections were prepared from resected tissue and DNA was extracted for molecular OncoScan analysis. RESULTS : Histological and immunochemical analysis showed a p16-negative poorly differentiated keratinizing squamous cell carcinoma. OncoScan analysis of this tumor revealed a high confidence TP53:p.R213*:c.637C>T somatic mutation as well as copy number alterations of chromosomal regions including gains of 1p, 3q, 5p, 7p, 8p, 8q, 11q, 15q, 17q, and 20p, and losses on 1p, 3p, 18q, and 22q. CONCLUSION : The TP53:p.R213*:c.637C>T mutation detected is indicative of a genetic predisposition to cancer and it is the first to be reported in TSCC in a nonsmoking young adult.https://onlinelibrary.wiley.com/journal/23788038am2020ImmunologyOral Pathology and Oral Biolog

Heterozygosity of p16 expression in an oral squamous cell carcinoma with associated loss of heterozygosity and copy number alterations

BACKGROUND : Oral field cancerization describes a multifocal development process involving many cells at once in response to prolong exposure to carcinogens. This case demonstrated differential p16 expression in different sections of the same HPV negative tumor on the floor of mouth in a patient with history of prolonged smoking. METHODS : Histological examination, presence of HPV infection and OncoScan analysis of DNA extracted from two well‐defined areas with different p16 expression profiles were performed. RESULTS : Histological and immunochemical analysis revealed the presence of a dual architectural pattern squamous cell carcinoma with a p16 negative and a p16 positive component. OncoScan analysis showed genetic changes that define field cancerization of the p16 negative tumor as revealed by mosaicism in both loss of heterozygosity and copy number alterations in cancer‐associated genes located on 3p, 7p, 9p 11q, and 17p. CONCLUSION : These changes were indicative of field cancerization in response to tobacco exposure.South African Medical Research Council (MSP); Cancer Association of South Africa (WFPvH)http://wileyonlinelibrary.com/journal/hed2019-12-14hj2019ImmunologyOral Pathology and Oral Biolog

Amplification of 3q26.2, 5q14.3, 8q24.3, 8q22.3, and 14q32.33 are possible common genetic Alterations in oral cancer patients

The lack of clinical biomarkers for head and neck cancer subtypes limits early diagnosis and monitoring of disease progression. This study investigates genetic alterations in clinically identical tumor, tumor-adjacent dysplastic epithelium (TADE) and normal epithelium (NE) in five oral cancer patients to identify differences and commonalities between oral cancer, TADE and NE. A VELscope®Vx device was used to identify TADE and NE surrounding a clinical tumor for analysis of genetic alterations using the OncoScan® assay. One of the tumor samples examined was an “M” class tumor with a high confidence BRAF:p.G469A:c.1406G>C somatic mutation, which is the first to be reported in oral cancer. Another tumor showed mosaicism in genetic alterations, indicating the presence of multiple clones. Overall, each patient’s tumor, TADE and NE showed a distinct genetic profile which indicates intertumoral clonal/genetic diversity. Interestingly, four tumors showed gain of 3q26.2, 5q14.3, 8q24.3, 8q22.3, 14q32.33 and loss/LOH in 9p21.3 while all TADE had LOH on 22q11.23. In addition, some genetic alterations progressed from NE through TADE into tumor in individual patients. Furthermore, no molecular event was identified that is common to all NE and/or TADE that progressed into tumor. This pilot study demonstrates the presence of genetic heterogeneity in oral tumorigenesis, and suggests that there might exist some common genetic alterations between tumors and TADE. However, this observation would need to be further investigated and validated in a larger cohort of oral cancer patients for its potential role in oral tumorigenesis.ormal epitheliumThis work was funded by the Cancer Association of South Africa (WFPvH) and the South African Medical Research Council (MSP—Flagship and Extramural Stem Cell Unit).http://www.frontiersin.org/Oncologyam2020ImmunologyOral Pathology and Oral Biolog

Slc7a8 deletion is protective against diet-induced obesity and attenuates lipid accumulation in multiple organs

Adipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giving rise to obesity. A genome-wide transcriptome analysis of in vitro adipogenesis in human adipose-derived stromal/stem cells identified SLC7A8 (Solute Carrier Family 7 Member 8) as a potential novel mediator. The current study has investigated the role of SLC7A8 in adipose tissue biology using a mouse model of diet-induced obesity. slc7a8 knockout (KO) and wildtype (WT) C57BL/6J mice were fed either a control diet (CD) or a high-fat diet (HFD) for 14 weeks. On the HFD, both WT and KO mice (WTHFD and KOHFD) gained significantly more weight than their CD counterparts. However, KOHFD gained significantly less weight than WTHFD. KOHFD had significantly reduced levels of glucose intolerance compared with those observed in WTHFD. KOHFD also had significantly reduced adipocyte mass and hypertrophy in inguinal, mesenteric, perigonadal, and brown adipose depots, with a corresponding decrease in macrophage infiltration. Additionally, KOHFD had decreased lipid accumulation in the liver, heart, gastrocnemius muscle, lung, and kidney. This study demonstrates that targeting slc7a8 protects against diet-induced obesity by reducing lipid accumulation in multiple organs and suggests that if targeted, has the potential to mitigate the development of obesity-associated comorbiditiesSupplementary Materials: Supplementary method S1: Genotyping of mice, Figure S1: Mice in study, Figure S2: Adipocyte hypertrophy at 5 weeks, Figure S3: Lipid droplets in the liver at 5 weeks, Figure S4: Perimuscular adipose tissue in gastrocnemius muscle at 5 weeks, Figure S5: Accumulation of adipose tissue in the lungs, Figure S6: Adipocyte diameter between white adipose tissue depots.National Research Foundation, National Health Laboratory Services, South African Medical Research Council University Flagship Project, SAMRC Extramural Unit for Stem Cell Research and Therapy and the Institute for Cellular and Molecular Medicine of the University of Pretoria.http://www.mdpi.com/journal/biologyImmunologyOral Pathology and Oral Biolog

Effect of 2-methoxyestradiol treatment on early- and late-stage breast cancer progression in a mouse model

DATA AVAILABILITY STATEMENT : The data supporting the results cited in the text can be found in the relevant articles cited in the references.The prevalence of breast cancer (BC) continues to increase and is the leading cause of cancer deaths in many countries. Numerous in vitro and in vivo studies have demonstrated that 2‐methoxyestradiol (2‐ME) has antiproliferative and antiangiogenic effects in BC, thereby inhibiting tumour growth and metastasis. We compared the effect of 2‐ME in early‐ and late‐stage BC using a transgenic mouse model— FVB/N‐Tg(MMTV‐PyVT)—of spontaneously development of aggressive mammary carcinoma with lung metastasis. Mice received 100 mg/kg 2‐ME treatment immediately when palpable mammary tumours were identified (early‐stage BC; Experimental group 1) and 28 days after palpable mammary tumours were detected (late‐stage BC; Experimental group 2). 2‐ME was administered via oral gavage three times a week for 28 days after initiation of treatment, whereas control mice received the vehicle containing 10% dimethyl sulfoxide and 90% sunflower oil for the same duration as the treatment group. Mammary tumours were measured weekly over the 28 days and at termination, blood, mammary and lung tissue were collected for analysis. Mice with a tumour volume threshold of 4000mm3 were killed before the treatment regime was completed. 2‐ME treatment of early‐stage BC led to lower levels of mammary tumour necrosis, whereas tumour mass and volume were increased. Additionally, necrotic lesions and anti‐inflammatory CD163‐expressing cells were more frequent in pulmonary metastatic tumours in this group. In contrast, 2‐ME treatment of late‐stage BC inhibited tumour growth over the 28‐day period and resulted in increased CD3+ cell number and tumour necrosis. Furthermore, 2‐ME treatment slowed down pulmonary metastasis but did not increase survival of late‐stage BC mice. Besides late‐stage tumour necrosis, none of the other results were statistically significant. This study demonstrates that 2‐ME treatment has an antitumour effect on late‐stage BC, however, with no increase in survival rate, whereas the treatment failed to demonstrate any benefit in early‐stage BC.The South African Medical Research Council Self‐Initiated Research Grant, the National Research Foundation Competitive Support for Unrated Researchers, the South African Medical Research Council University Flagship Project, the SAMRC Extramural Unit for Stem Cell Research and Therapy and the Institute for Cellular and Molecular Medicine of the University of Pretoria.http://wileyonlinelibrary.com/journal/cbfam2024ImmunologyOral Pathology and Oral BiologyPhysiologySDG-03:Good heatlh and well-bein

Oral plasmablastic lymphoma : a clinicopathological study of 113 cases

BACKGROUND : Plasmablastic lymphoma (PBL) is an aggressive neoplasm that commonly develops in HIV-positive patients, usually affecting the oral cavity. EBV is present in the majority of cases, therefore, playing an important role in the pathogenesis of this neoplasm. METHODS : PBL diagnosed from 2000 to 2020 were retrieved from the archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria, South Africa. The patients’ clinical information including gender, age, tumour location and HIV status was obtained from the original histopathology request forms. A morphological description was assessed using H&E-stained slides, with diagnoses confirmed by immunohistochemistry, and EBV detection performed via in situ hybridisation. RESULTS : During the 20 years period investigated, 113 PBL were found. Males outnumbered females (M:F ratio of 3:1), with a median age of 41 years (range 8–62). The gingiva (50 cases or 44.2%) and the palate (23 cases or 20.4%) were the most affected sites. All cases with available information were HIV positive. The tumours were composed of a diffuse proliferation of immunoblasts or plasmablasts in all cases. A starry-sky pattern, tissue necrosis, cellular pleomorphism and mitotic figures were common microscopic findings. IHC for CD3 and CD20 were negative in all cases, while positivity for CD38, CD138 and MUM1 was observed in 70.2%, 79.2% and 98.9%, respectively. EBV was present in 100% of the cases. CONCLUSION : PBL is a frequent diagnosis in South Africa, due to the country's HIV burden, where it usually affects the oral cavity and is always associated with EBV infection.http://www.wileyonlinelibrary.com/journal/jopam2022Oral Pathology and Oral Biolog

Oral plasmablastic lymphoma: A clinicopathological study of 113 cases

BACKGROUND : Plasmablastic lymphoma (PBL) is an aggressive neoplasm that commonly develops in HIV-positive patients, usually affecting the oral cavity. EBV is present in the majority of cases, therefore, playing an important role in the pathogenesis of this neoplasm. METHODS : PBL diagnosed from 2000 to 2020 were retrieved from the archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria, South Africa. The patients’ clinical information including gender, age, tumour location and HIV status was obtained from the original histopathology request forms. A morphological description was assessed using H&E-stained slides, with diagnoses confirmed by immunohistochemistry, and EBV detection performed via in situ hybridisation. RESULTS : During the 20 years period investigated, 113 PBL were found. Males outnumbered females (M:F ratio of 3:1), with a median age of 41 years (range 8–62). The gingiva (50 cases or 44.2%) and the palate (23 cases or 20.4%) were the most affected sites. All cases with available information were HIV positive. The tumours were composed of a diffuse proliferation of immunoblasts or plasmablasts in all cases. A starry-sky pattern, tissue necrosis, cellular pleomorphism and mitotic figures were common microscopic findings. IHC for CD3 and CD20 were negative in all cases, while positivity for CD38, CD138 and MUM1 was observed in 70.2%, 79.2% and 98.9%, respectively. EBV was present in 100% of the cases. CONCLUSION : PBL is a frequent diagnosis in South Africa, due to the country's HIV burden, where it usually affects the oral cavity and is always associated with EBV infection.http://www.wileyonlinelibrary.com/journal/jopam2022Oral Pathology and Oral Biolog

Molecular profile of tongue cancer in an 18‐year‐old female patient with no recognizable risk factor

BACKGROUND : The occurrence of oral tongue squamous cell carcinoma (TSCC) in nonsmoking young adults, especially females, has increased. Yet, there is no clear evidence to support the existence of any single determinant. This case reports the presence of TSCC in an 18-year-old female with no recognizable risk factor for oral cancer development. METHODS : Histological examination and p16 immunohistochemistry were performed. Formalin-fixed paraffin-embedded sections were prepared from resected tissue and DNA was extracted for molecular OncoScan analysis. RESULTS : Histological and immunochemical analysis showed a p16-negative poorly differentiated keratinizing squamous cell carcinoma. OncoScan analysis of this tumor revealed a high confidence TP53:p.R213*:c.637C>T somatic mutation as well as copy number alterations of chromosomal regions including gains of 1p, 3q, 5p, 7p, 8p, 8q, 11q, 15q, 17q, and 20p, and losses on 1p, 3p, 18q, and 22q. CONCLUSION : The TP53:p.R213*:c.637C>T mutation detected is indicative of a genetic predisposition to cancer and it is the first to be reported in TSCC in a nonsmoking young adult.https://onlinelibrary.wiley.com/journal/23788038am2020ImmunologyOral Pathology and Oral Biolog

Heterozygosity of p16 expression in an oral squamous cell carcinoma with associated loss of heterozygosity and copy number alterations

BACKGROUND : Oral field cancerization describes a multifocal development process involving many cells at once in response to prolong exposure to carcinogens. This case demonstrated differential p16 expression in different sections of the same HPV negative tumor on the floor of mouth in a patient with history of prolonged smoking. METHODS : Histological examination, presence of HPV infection and OncoScan analysis of DNA extracted from two well‐defined areas with different p16 expression profiles were performed. RESULTS : Histological and immunochemical analysis revealed the presence of a dual architectural pattern squamous cell carcinoma with a p16 negative and a p16 positive component. OncoScan analysis showed genetic changes that define field cancerization of the p16 negative tumor as revealed by mosaicism in both loss of heterozygosity and copy number alterations in cancer‐associated genes located on 3p, 7p, 9p 11q, and 17p. CONCLUSION : These changes were indicative of field cancerization in response to tobacco exposure.South African Medical Research Council (MSP); Cancer Association of South Africa (WFPvH)http://wileyonlinelibrary.com/journal/hed2019-12-14hj2019ImmunologyOral Pathology and Oral Biolog

Comparative molecular genetics of odontogenic keratocysts in sporadic and syndromic patients

DATA AVAILABILITY STATEMENT : All data generated or analyzed during this study are included in this published article.Odontogenic keratocysts (OKCs) are common cysts of odontogenic origin that usually occur as a single nonsyndromic cyst in isolation (sporadic) or as syndromic multiple cysts as a manifestation of naevoid basal cell carcinoma syndrome. Alterations involving the PTCH gene are the most commonly identified factor associated with up to 85% and 84% of naevoid basal cell carcinoma syndrome and sporadic cases, respectively. Other Hedgehog pathway and non-Hedgehog pathway-associated genes have been implicated in the pathogenesis of OKCs. This pilot study used the Affymetrix OncoScan molecular assay to perform a comparative genomic analysis between 4 sporadic and 3 syndromic cases of OKC to identify molecular drivers that may be common and/or distinct in these 2 groups. The majority of alterations detected in both groups were copy number neutral loss of heterozygosity. Despite distinct molecular signatures observed in both groups, copy number neutral loss of heterozygosity alterations involving chromosome 9q affecting not only PTCH but also the NOTCH1 gene were detected in all syndromic and 3 sporadic cases. Loss of heterozygosity alterations involving 16p11.2 affecting genes not previously described in OKCs were also detected in all syndromic and 3 sporadic cases. Furthermore, alterations on 22q11.23 and 10q22.1 were also detected in both groups. Of note, alterations on 1p13.3, 2q22.1, and 6p21.33 detected in sporadic cases were absent in all syndromic cases. This study demonstrates that a more common group of genes may be affected in both groups of OKCs, whereas other alterations may be useful in distinguishing sporadic from syndromic cysts. These findings should be validated in larger OKC cohorts to improve molecular diagnosis and subsequent patient management.The Cancer Association of South Africa and the South African Medical Research Council.https://modernpathology.org2024-01-18hj2023ImmunologyOral Pathology and Oral Biolog