Oral Squamous Cell Carcinoma in Cats

The aim of the study is to examine cases of oral squamous cell carcinoma in cats based on clinical and morphological data and analysis of current literature. Objectives: to systematize information on risk factors and molecular drivers of FOSCC; to substantiate algorithms for staging and locoregional monitoring of FOSCC; to characterize cytomorphological features of oral squamous cell carcinoma and regional lymph nodes in cats. A series of five clinical cases of FOSCC were analyzed in combination with a narrative review of the literature to characterize clinical, macro- and microscopic and cytological features, staging algorithms and treatment options with outcome assessment. All patients underwent clinical examination, imaging, bilateral fine-needle aspiration of mandibular lymph nodes and histological verification of the diagnosis using H&E stains (with decalcification when necessary). Main outcomes: overall survival (OS), mitotic index (MI), regional node status and the presence of bone invasion. Descriptive statistics, the Mann–Whitney test, Cliff's δ, and the Kaplan–Meier estimate were used. Ulcerative-infiltrative gingival lesions predominated. Significant bone invasion was detected in 80 % of cases (T4 according to the veterinary modification of TNM staging), while no bone invasion was detected in 20 % of cases (T3 according to the overall assessment). Keratinization in tumor complexes was absent or minimal (nonkeratinizing spectrum), which is consistent with the aggressive local course of this nosology in cats. Intercellular bridges and focal signs of desmoplasia were observed in all preparations. Mitotic activity ranged from 2 to 5 mitoses per 10 fields of view at standard magnification, with a median of 3/10 fields of view (Q1-Q3: 2–4), which corresponds to a low-moderate level of proliferation for squamous cell carcinomas in this location. The findings highlight the osteoinvasive nature of FOSCC, the clinically significant incidence of regional node involvement, and the need for standardized staging (bilateral node aspiration and chest imaging) with a multidisciplinary focus on local control and quality of life.

This study describes the clinical and pathological characteristics of cutaneous spindle cell squamous cell carcinoma (SCSCC) in 18 cats. The average age of the cats was 11.8 ± 2.7 years, and all tumors were located in the facial skin, mainly affecting the pinna (13/18, 72%), followed by the periorbital area (4/18, 22%) and the dorsal muzzle (1/18, 6%). Tumors were composed of fusiform neoplastic cells with moderate atypia arranged in solid sheets or fascicles with foci of squamous differentiation. A panel of antibodies against cytokeratins, vimentin, S-100 protein, NSE, GFAP, Melan A, SMA, desmin, CD18, CD31, and p63 was used to help differentiate SCSCC from other spindle cell malignancies. SCSCCs expressed CK5/6 (17/18, 94%), AE1/AE3 (15/18, 83%), and p63 protein (18/18, 100%), but there was no immunolabeling for CK8/18. A role for sunlight exposure in the pathogenesis of the tumors was suggested by changes indicative of actinic keratosis, the location of the tumors in dorsal areas, and the absence of histomorphologic features of papillomavirus infection. Recurrence was not recorded in 14/18 cases (78%) during a follow-up period of 7 to 25 months. Three of 18 (17%) tumors recurred or led to humane euthanasia due to local progression, and one case (5%) had regional lymph node metastasis. Clinical outcome varied with cutaneous location, mitotic count, and invasion of surgical margins; thus, SCSCCs with a more aggressive behavior were located in the periorbital area (4/4 cases), had ≥14 mitoses in 10 high-power fields (2.37 mm2) (4/4 cases), and showed invasion of surgical margins (3/4 cases).

O carcinoma de células escamosas é uma neoplasia cutânea de grande relevância em países de clima tropical como o Brasil, uma vez que a exposição crônica à radiação ultravioleta é um dos fatores importantes para o desenvolvimento da doença. Esta revisão tem por objetivo discorrer sobre alternativas de tratamento do carcinoma de células escamosas em gatos, com ênfase à terapia fotodinâmica. A escolha da modalidade terapêutica deve ser estabelecida de acordo com o estadiamento do tumor, o estado geral do paciente, a colaboração do proprietário e a disponibilidade de equipamentos e fármacos. A precocidade no diagnóstico tem efeito fundamental no prognóstico.

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Expression of KITENIN and its association with tumor progression in oral squamous cell carcinoma

Simple SummaryWe aimed to estimate the effects of preexisting sleep disorders on the oncologic outcomes of patients with oral squamous cell carcinoma (OSCC) after receiving standard treatments. We conducted a head-to-head propensity-score-matching-based study to mimic a randomized trial to compare the survival, locoregional recurrence, and distant metastasis rates between OSCC patients with and without sleep disorders. The patients with sleep disorders receiving curative treatments for OSCC had poorer oncologic outcomes than did those without sleep disorders. Preexisting sleep disorders may be survival predictors in patients with OSCC. Studies on how pharmacological and behavioral treatments for sleep problems improve survival benefits in patients with OSCC are warranted.Purpose: To investigate the effects of preexisting sleep disorders on the oncologic outcomes of patients receiving standard treatments for oral squamous cell carcinoma (OSCC). Methods: The patients recruited from the Taiwan Cancer Registry Database who had received surgery for stage I–IVB OSCC. The Cox proportional hazards model was used to analyze all-cause mortality, locoregional recurrence (LRR), and distant metastasis (DM). The patients were categorized into those with and without sleep disorders (Groups 1 and 2, respectively) through propensity score matching. Results: In the multivariate Cox regression analysis, the adjusted hazard ratios for all-cause mortality, LRR, and DM for Group 1 compared with Group 2 were 1.19 (95% confidence interval (CI): 1.04–1.36; p = 0.011), 1.47 (95% CI: 1.23–1.75; p < 0.001), and 1.15 (95% CI: 1.02–1.44; p = 0.025), respectively. Conclusion: OSCC patients with sleep disorders demonstrated poorer oncologic outcomes than did those without sleep disorders. Therefore, before OSCC surgery, patients with OSCC should be screened for preexisting sleep disorders because they may serve as predictors for survival in these patients. Future studies investigating the survival benefits of pharmacological and behavioral treatments for sleep problems in patients with OSCC are warranted.

The TNM staging system for oral squamous cell carcinoma (OSCC) provides clinicians a dependable foundation for patient prognosis and management decisions, but in clinical practice, treatment outcomes of patients with OSCC are sometimes unsatisfactory. This retrospective study investigated the association between survival and clinicopathological characteristics and histological grades of 2535 patients with OSCC. Additionally, the present study aimed to compare the predictive abilities of histological grades with other common prognostic factors. The enrolled patients were divided into three groups by two experienced pathologists into well-differentiated, moderately differentiated, and poorly differentiated groups, according to the WHO classification. Finally, we designed an observational, retrospective study based on the histological grading of tumors to compare their clinicopathological characteristics and conducted survival analysis among the three groups. Advanced tumor stage was diagnosed in 23.9%, 44.0%, and 55.1% of patients with grades 1-3 OSCC, respectively. By T status, T3 or T4 tumors were found in approximately 22%, 34%, and 40% of patients with grades 1-3 OSCC, respectively. By N status, lymph node metastases were found in 6.1%, 29.3%, and 45.9% of patients with grades 1-3 OSCC, respectively. Thus, significant survival differences were observed based on different OSCC histological grades. Meanwhile, in the multivariate (adjusted) analysis, N1 and N2 stages, extranodal spread, and poor differentiation were associated with a higher recurrence risk than the other common prognostic factors. In conclusion, 5% of patients in our study presented with poorly differentiated OSCC at diagnosis. Furthermore, grade 3 OSCC has worse prognosis and is more aggressive than grades 1 and 2 OSCC. In the future, we should focus on modifying individual therapy for poorly differentiated OSCC to achieve improved outcomes.

The TNM staging system for oral squamous cell carcinoma (OSCC) provides clinicians a dependable foundation for patient prognosis and management decisions, but in clinical practice, treatment outcomes of patients with OSCC are sometimes unsatisfactory. This retrospective study investigated the association between survival and clinicopathological characteristics and histological grades of 2535 patients with OSCC. Additionally, the present study aimed to compare the predictive abilities of histological grades with other common prognostic factors. The enrolled patients were divided into three groups by two experienced pathologists into well-differentiated, moderately differentiated, and poorly differentiated groups, according to the WHO classification. Finally, we designed an observational, retrospective study based on the histological grading of tumors to compare their clinicopathological characteristics and conducted survival analysis among the three groups. Advanced tumor stage was diagnosed in 23.9%, 44.0%, and 55.1% of patients with grades 1–3 OSCC, respectively. By T status, T3 or T4 tumors were found in approximately 22%, 34%, and 40% of patients with grades 1–3 OSCC, respectively. By N status, lymph node metastases were found in 6.1%, 29.3%, and 45.9% of patients with grades 1–3 OSCC, respectively. Thus, significant survival differences were observed based on different OSCC histological grades. Meanwhile, in the multivariate (adjusted) analysis, N1 and N2 stages, extranodal spread, and poor differentiation were associated with a higher recurrence risk than the other common prognostic factors. In conclusion, 5% of patients in our study presented with poorly differentiated OSCC at diagnosis. Furthermore, grade 3 OSCC has worse prognosis and is more aggressive than grades 1 and 2 OSCC. In the future, we should focus on modifying individual therapy for poorly differentiated OSCC to achieve improved outcomes.

DPM1 expression as a potential prognostic tumor marker in oral squamous cell carcinoma.

Introduction: Several researchers have been stated that the right prognosis of oral squamous cell carcinoma (OSCC) can be achieved through assessment of tumor clinical staging and tumor histopathological grading as well. The use of biomarker in histopathological grading is obviously helpful to ensure the prognosis. Objective of this study was to determine the correlation between expression of Ki-67 and histopathological grading of OSCC. Methods: A retrospective study was conducted by assessing 20 cases of paraffin-embedded OSCC derived from the Department of Pathology Anatomy of Hasan Sadikin Hospital Bandung in 2013. The OSCC performing was stained by hematoxylin-eosin. While, antibodies Ki-67 was used in immunohistochemistry reaction to determine the relation of expression of Ki-67 with histopathologic grade of OSCC for predicting a prognosis. Results: The result show that distribution of Ki-67 expression were vary from 20% to 80% in each case. Ki-67 intensity was also distributed from weak, moderate and strong. Conclusion: There is a significant correlation between Ki-67 immunoexpression and the histopathological grading of squamous cell carcinoma (p &lt; 0.01), thus, Ki-67 can be used to predict a prognosis.Keywords: Immunoexpression, Ki-67, prognosis, oral cavity squamous cell carcinoma

Advances in cancer treatment have increased survival for many patients, prompting a need for greater recognition of the long-term complications of treatment. Chemotherapy agents have the potential to induce carcinogenesis and can increase the risk of secondary malignancy. Pegylated liposomal doxorubicin (PLD) used for maintenance treatment of recurrent high-grade serous cancers has been associated with the development of oral cavity squamous cell carcinoma (SCC). Retrospective review. Cases of oral cavity SCC in patients with recurrent high-grade serous cancer treated with PLD between 1997 and 2017 at a single institution were reviewed. Eight of 16 patients treated with PLD developed oral cavity SCC. The duration of PLD use ranged from 1.3 to 15 years (mean = 5.8 years) and cumulative dose ranged from 405 to 3,000 mg/m2 (mean = 1,542 mg/m2 ). Seven patients tested positive for BRCA mutations (four BRCA 1+, three BRCA 2+). No patients had a history of alcohol or tobacco use. All had early-stage oral cavity disease; five were T1N0, two were T2N0, and one had carcinoma in situ. All patients underwent surgery, and two received adjuvant radiation. Four developed locoregional recurrence requiring additional treatment. Of these, one patient died from complications of oral SCC, one developed recurrent ovarian cancer, and two had no evidence of disease of the oral cavity or ovarian cancer at the last follow-up. Long-term PLD therapy may be associated with the development of oral cavity SCC. A high index of suspicion and routine head and neck examination should be included in follow-up for exposed patients. 4 Laryngoscope, 130:2607-2610, 2020.

Carcinogenesis occurs when the cell cycle is compromised. Chromatin licensing and DNA replication factor 1, geminin, and γ-H2A histone family member X are expressed in cells in G1 phase, S/G2 /M phases, and apoptosis, respectively, and these three markers may be useful for histological evaluation of malignant lesions. Here, we aimed to identify cell cycle phases and apoptosis using immunohistochemistry in oral epithelial precursor lesions and oral squamous cell carcinoma. Chromatin licensing and DNA replication factor 1, geminin, and γ-H2A histone family member X expression levels were immunohistochemically examined in tissue specimens from 55 patients with oral epithelial precursor lesions and 50 patients with oral squamous cell carcinoma. Associations of clinicopathological variables with marker expression were assessed. Chromatin licensing and DNA replication factor 1 was expressed in the prickle cell layer of oral epithelial precursor lesions and many carcinoma cells of oral squamous cell carcinoma. Geminin reactivity was widely distributed in high-grade dysplasia and oral squamous cell carcinoma rather than low-grade or no dysplastic cases. γ-H2A histone family member X was expressed in the superficial layer of oral epithelial precursor lesions and scattered carcinoma cells of oral squamous cell carcinoma. In oral squamous cell carcinoma, lower geminin expression was observed in recurrent cases. Geminin and γ-H2A histone family member X were associated with the degree of differentiation and mode of invasion. Chromatin licensing and DNA replication factor 1, geminin, and γ-H2A histone family member X expression levels were correlated with oral carcinogenesis; these markers were associated with clinicopathological behaviors in oral squamous cell carcinoma.

TGF-β1rs1982073 polymorphism at the miRNA-187 binding site may alter TGF-β1 expression and function, and thereby this polymorphism (genotype CT/CC) increases cancer susceptibility. HPV16 L1 seropositivity is associated with the risk of oral squamous cell carcinoma (OSCC), including oropharyngeal squamous cell carcinoma (OPSCC) and oral cavity squamous cell carcinoma (OCSCC). Thus, we hypothesized that TGF-β1rs1982073 polymorphism at the miRNA-187 binding site combined with HPV16 L1 seropositivity may have a joint effect on OSCC susceptibility. We determined the genotypes of TGF-β1rs1982073 and HPV16 status in 325 OSCC subjects and 335 cancer-free controls in the non-Hispanic white population, and used logistic regression models to evaluate the joint effects on OSCC susceptibility. TGF-β1rs1982073 polymorphism (CT/CC genotype) combined with HPV16 L1 seropositivity increased the risk of OSCC via joint effects, particularly in OPSCC subjects who were never-smokers (OR, 165.9; 95% CI, 28.6-960.4) or never-drinkers (OR, 196.0; 95% CI, 28.2-1,000.0), respectively. Younger subjects had a higher risk of OPSCC than older subjects (OR, 23.5; 95% CI, 6.3-87.0 vs. OR, 6.0; 95% CI, 1.7-17.9, respectively). The significant associations between this polymorphism and HPV16-associated OSCC and OPSCC were also observed. However, OCSCC subjects did not have similar results. Our findings suggest that the joint effects of TGF-β1rs1982073 and HPV16 L1 seropositivity can increase risk of HPV16-associated oral cancer, particularly in OPSCC subjects who are never-smokers, never-drinkers and young. This result may help us understand the tumorigenesis process and improve early detection, which are critical for prevention and intervention strategies. However, larger studies are needed to validate our findings.

Oral squamous cell carcinoma (OSCC) is one of the common types of cancer. Its progression follows a transition from oral potentially malignant disorders (OPMDs) such as oral submucous fibrosis (OSMF). Epigenetic modifiers, especially microRNAs (miRNAs), have an appreciable role in the regulation of various carcinogenic pathways which are being used as biomarkers. miRNAs may also be helpful in the differentiation of oral submucous fibrosis from oral squamous cell carcinoma. Three miRNAs, miR-221-3p, miR133a-3p, and miR-9-5p, were found differentially expressed in many cancers in the literature search supported by our preliminary database search-based screening. The literature and our functional enrichment analysis in an earlier study have reported these miRNAs to regulate carcinogenesis at various steps. In the present study, the expression of these miRNAs was examined in 34 histopathologically confirmed OSCC, 30 OSMF, and 29 control (healthy volunteers) human samples. There was a significant downregulation of miRNA-133a-3p in OSCC compared to OSMF and controls, whereas there was up-regulation in oral submucous fibrosis compared to controls. There was no significant difference in the expression of miR-221-3p between OSCC and OSMF, but an upregulation in OSCC compared to controls. miR-9-5p was also found upregulated in both OSCC and OSMF. Further, miR-133a-3p expression was negatively correlated with age, smoking, drinking status, and AJCC staging, whereas miR-9-5p expression was only positively associated with tobacco/ areca nut chewing. The ROC plots, logistic regression model generated, and the correlation between the expression of miR-9-5p and miR-133a-3p in blood and tissue suggests that these could be used as risk stratification biomarkers.

Lin28, a key factor for cellular reprogramming and generation of induced pluripotent stem cell (iPSC), makes a critical contribution to tumorigenicity by suppressing Let-7. However, it is unclear whether Lin28 is involved in regulating cancer stem-like cells (CSC), including in oral squamous carcinoma cells (OSCC). In this study, we demonstrate a correlation between high levels of Lin28B, Oct4, and Sox2, and a high percentage of CD44(+)ALDH1(+) CSC in OSCC. Ectopic Lin28B expression in CD44(-)ALDH1(-)/OSCC cells was sufficient to enhance Oct4/Sox2 expression and CSC properties, whereas Let7 co-overexpression effectively reversed these phenomena. We identified ARID3B and HMGA2 as downstream effectors of Lin28B/Let7 signaling in regulating endogenous Oct4 and Sox2 expression. Let7 targeted the 3' untranslated region of ARID3B and HMGA2 and suppressed their expression, whereas ARID3B and HMGA2 increased the transcription of Oct4 and Sox2, respectively, through promoter binding. Chromatin immunoprecipitation assays revealed a direct association between ARID3B and a specific ARID3B-binding sequence in the Oct4 promoter. Notably, by modulating Oct4/Sox2 expression, the Lin28B-Let7 pathway not only regulated stemness properties in OSCC but also determined the efficiency by which normal human oral keratinocytes could be reprogrammed to iPSC. Clinically, a Lin28B(high)-Let7(low) expression pattern was highly correlated with high levels of ARID3B, HMGA2, OCT4, and SOX2 expression in OSCC specimens. Taken together, our results show how Lin28B/Let7 regulates key cancer stem-like properties in oral squamous cancers.