Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura / Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review / Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

Injerto de piel libre como tratamiento exitoso de una úlcera de Marjolin / Free skin graft as a successful treatment of a Marjolin ulcer

Introducción: la úlcera de Marjolin hace referencia a la aparición de un carcinoma de células escamosas ulcerado sobre un área previamente lesionada, crónicamente inflamada o con cicatrices. Se estima que solo el 1,7 % de las heridas crónicas se malignizan. Caso clínico: se trata de una mujer de 76 años que presentó una úlcera venosa crónica en la región maleolar de diez años de evolución que se había extendido. Se realizó una biopsia insicional y se obtuvo un carcinoma de células escamosas, por lo que se realizó la resección del tejido afectado, cubriendo el área con injerto autólogo de piel libre, fenestrado, de espesor parcial, y posteriormente se realizaron curas durante la hospitalización y el manejo ambulatorio, con lo que se obtuvieron resultados satisfactorios. Discusión: la resección-desbridamiento quirúrgico de la úlcera de Marjolin y el cierre con injerto libre de piel permitió la evolución satisfactoria y la cicatrización de las lesiones.(AU)

Introduction: Marjolin’s ulcer refers to the appearance of ulcerated squamous cell carcinoma on a previously injured,chronically inflamed or scarred area; it is estimated that only 1.7 % of chronic wounds become malignant.Case report: this is a 76-year-old woman who presented a chronic venous ulcer in the malleolar region of ten years ofevolution that had spread. An incisional biopsy was taken, resulting in squamous cell carcinoma, for which resectionof the affected tissue was performed: the area was covered with a free, fenestrated, partial-thickness autologous skingraft. Later, cures were carried out during hospitalization and ambulatory management, obtaining satisfactory results.Discussion: the surgical resection-debridement of the Marjolin ulcer and the closure with a free skin graft allowed thesatisfactory evolution and healing of the lesions.(AU)

Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors / Impacto de la pandemia de COVID-19 en el carcinoma de células escamosas cutáneo: un estudio unicéntrico de los factores epidemiológicos, clínicos e histopatológicos

Background: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. Objective To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. Material & methods: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. Results: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. Conclusions: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future. (AU)

Antecedentes: La pandemia de COVID-19 ha podido afectar negativamente el diagnóstico precoz del cáncer de piel. Objetivo Comparar las características epidemiológicas, clínicas e histopatológicas en los pacientes intervenidos de carcinoma de células escamosas (CCE) cutáneo antes de la pandemia y después del inicio de la pandemia. Material y métodos: Se diseñó un estudio transversal que incluía 2 series de pacientes: 1) pacientes intervenidos de CCE el año posterior a la declaración del confinamiento general en España (15 de marzo de 2020), y 2) pacientes intervenidos de CCE el año previo. Se recogieron variables epidemiológicas, clínicas e histopatológicas, así como el estadio tumoral y el grado de riesgo. Resultados: Se incluyeron 248 pacientes (127 intervenidos antes de la pandemia y 121 intervenidos después de la pandemia). Tras el inicio de la pandemia, el porcentaje de CCE de alto riesgo aumentó significativamente de 32,3 a 45,5% (p=0,011). No obstante, no se encontraron diferencias significativas en el grosor tumoral, la invasión perineural o la presencia de metástasis. Conclusiones: Aunque no se produjo una reducción significativa en el número de CCE intervenidos después de la pandemia, ha habido un incremento significativo en los CCE de alto riesgo. Todo ello puede conllevar un incremento en la mortalidad por cáncer de piel en el futuro. (AU)

[Artículo traducido] Impacto de la pandemia COVID-19 en el carcinoma de células escamosas cutáneo: un estudio unicéntrico de los factores epidemiológicos, clínicos e histopatológicos / Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors

Antecedentes: La pandemia de COVID-19ha podido afectar negativamente el diagnóstico precoz del cáncer de piel. Objetivo Comparar las características epidemiológicas, clínicas e histopatológicas en los pacientes intervenidos de carcinoma de células escamosas (CCE) cutáneo antes de la pandemia y después del inicio de la pandemia. Material y métodos: Se diseñó un estudio transversal que incluía 2 series de pacientes: 1) pacientes intervenidos de CCE el año posterior a la declaración del confinamiento general en España (15 de marzo de 2020), y 2) pacientes intervenidos de CCE el año previo. Se recogieron variables epidemiológicas, clínicas e histopatológicas, así como el estadio tumoral y el grado de riesgo. Resultados: Se incluyeron 248 pacientes (127 intervenidos antes de la pandemia y 121 intervenidos después de la pandemia). Tras el inicio de la pandemia, el porcentaje de CCE de alto riesgo aumentó significativamente de 32,3 a 45,5% (p=0,011). No obstante, no se encontraron diferencias significativas en el grosor tumoral, la invasión perineural o la presencia de metástasis. Conclusiones: Aunque no se produjo una reducción significativa en el número de CCE intervenidos después de la pandemia, ha habido un incremento significativo en los CCE de alto riesgo. Todo ello puede conllevar un incremento en la mortalidad por cáncer de piel en el futuro. (AU)

Background: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. Objective To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. Material & methods: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. Results: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. Conclusions: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future. (AU)

Analysis of the Clinicopathological Characteristics and Prognosis of Patients with Nonurothelial Bladder Cancer

Background: Due to the low incidence of nonurothelial bladder cancer (NUBC), there is limited evidence in the field of evidence-based medicine regarding treatment modalities for such diseases. The purpose of our study was to explore the clinicopathological characteristics and prognostic factors of NUBC. Methods: We retrospectively analyzed the clinical data of 135 bladder squamous cell carcinoma (SqCC) and adenocarcinoma (AC) patients treated at the Second Hospital of Tianjin Medical University between October 2011 and February 2022, including 70 SqCC and 65 AC patients; We also analyzed 145 patients from the Surveillance, Epidemiology, and End Results (SEER) database from 2011 to 2020, including 108 SqCC and 37 AC patients. Clinicopathological characteristics and prognoses were compared between the SqCC and AC groups. Additionally, the Kaplan‒Meier method and log-rank tests were used to perform survival analysis, and the Cox proportional hazard model was applied to analyze clinical factors affecting prognosis. Results: Comparisons of clinicopathological characteristics between the SqCC and AC groups revealed that age at diagnosis (p < 0.001, p < 0.001), tumor diameter (p < 0.001), tumor location (p = 0.002), and surgical approach (p < 0.001) were significantly different. Univariate and multivariate Cox regression analyses indicated that lymph node metastasis (p = 0.031), advanced pT stage (p < 0.001), and SqCC (p < 0.001) were independent risk factors affecting the prognosis of NUBC patients, and comparisons of clinicopathological characteristics between the SqCC and AC groups from the SEER database revealed that tumor diameter (p < 0.001), tumor location (p = 0.033), tumor number (p = 0.004), surgical approach (p = 0.005), and lymph node metastasis (p = 0.017) were statistically significant... (AU)

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma

Purpose To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). Method and materials All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8 years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. Results ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5 days, P = 0.042) than in the MF group. Conclusion The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC (AU)

NPHS2-6 drives cervical squamous cell carcinoma (CSCC) progression via hsa-miR-1323/SMC1B axis to activate PI3K-Akt pathway

Purpose A substantial amount of evidence demonstrates suggests that long non-coding RNAs (lncRNAs) play a key role in the progression of various malignancies, cervical squamous cell carcinoma (CSCC) included. In our study, we deeply investigated the role and molecular mechanism of lncRNA NPHS2-6 in CSCC. Methods The expression level of gene and protein expression were measured by qRT-PCR and western blot. To test the cell proliferation and cell metastasis ability, we carried out the CCK-8 experiment, clone formation assay, transwell assay and wound healing, respectively. The interactivity among NPHS2-6, miR-1323 and SMC1B were co demonstrated using the bioinformatics tool, dual-luciferase reporter system, and RNA pulldown assay. The subcutaneous tumor model of nude mice was established to verify the results of previous studies at the in vivo. NPHS2-6 was upregulated in CSCC tissues and cells. Results NPHS2-6 deficiency significantly inhibited CSCC cell growth and EMT in vitro. In addition, NPHS2-6 deficiency also inhibited the growth of CSCC xenograft tumors in mice in vivo. Importantly, NPHS2-6 was a competing endogenous RNA (ceRNA) to increases SMC1B levels by binding to miR-1323, leading to activate the PI3K/Akt pathway, thereby exacerbating tumorigenesis of CSCC. Conclusions In conclusion, NPHS2-6/miR-1323/SMC1B/PI3K/Akt signaling accelerates the progression of CSCC, providing a new direction for the treatment strategy of CSCC (AU)

The expression of corticotropin-releasing hormone family peptides in premalignant and malignant vulvar lesions

Objectives To examine the relation of corticotropin-releasing hormone (CRH) family peptides with inflammatory processes and oncogenesis, emphasizing in vulvar inflammatory, premalignant and malignant lesions, as well as to investigate the possibility of lesion cells immunoescaping, utilizing FAS/FAS-L complex. Methods Immunohistochemical expression of CRH, urocortin (UCN), FasL and their receptors CRHR1, CRHR2 and Fas was studied in vulvar tissue sections obtained from patients with histologically confirmed diagnosis of lichen, vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell carcinoma (VSCC). The patient cohort was selected from a tertiary teaching Hospital in Greece, between 2005 and 2015. For each of the disease categories, immunohistochemical staining was evaluated and the results were statistically compared. Results A progressive increase of the cytoplasmic immunohistochemical expression of CRH and UCN, from precancerous lesions to VSCC was observed. A similar increase was detected for Fas and FasL expression. Nuclear localization of UCN was demonstrated in both premalignant and VSCC lesions, with staining being significantly intensified in carcinomas, particularly in the less differentiated tumor areas or in the areas at invasive tumor front. Conclusions Stress response system and CRH family peptides seem to have a role in inflammation maintenance and progression of vulvar premalignant lesions to malignancy. It seems that stress peptides may locally modulate the stroma through Fas/FasL upregulation, possibly contributing to vulvar cancer development (AU)

Epidemiological, clinical, and prognostic analysis of oral squamous cell carcinoma diagnosed and treated in a single hospital in Galicia (Spain): a retrospective study with 5-year follow-up / Análisis epidemiológico, clínico y pronóstico del carcinoma oral de células escamosas diagnosticado y tratado en un único hospital de Galicia (España): un estudio retrospectivo con un seguimiento de 5 años

Background: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma(OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study,we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specificSpanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosismeasures.Material and Methods: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospitalcentre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival werecalculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression).Results: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) andalcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailedthe 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC casesreferred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with anoral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatmen. Conclusions: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prog-nosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights thebetter survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and thedental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the earlydiagnosis and multidisciplinary management of this malignant neoplasm.(AU)

CISD2 promotes lung squamous carcinoma cell migration and invasion via the TGF-B1-induced Smad2/3 signaling pathway

Background Although aberrant expression of CDGSH iron sulfur domain 2 (CISD2) contributes to the tumorigenesis and progression of numerous human cancers, the biological function of CISD2 and its specific prognostic value in lung squamous cell carcinoma (LUSC) have yet to be comprehensively explored. The current study aimed to elucidate the role of CISD2 in LUSC as well as the underlying molecular mechanisms. Methods Immunohistochemistry was conducted to detect the protein expression of CISD2 and analyze whether high expression of CISD2 affects the overall survival (OS) of LUSC patients. Cell proliferation, colony formation, wound healing and Transwell invasion assays were performed to clarify whether CISD2 contributes to LUSC cell proliferation and disease progression. Quantitative real-time reverse transcription-PCR and western blot assays were used to detect the levels of transcription factors and key epithelial-mesenchymal transition (EMT)-related markers in LUSC cells after CISD2 knockdown and overexpression to determine whether CISD2 regulates transforming growth factor-beta (TGF-β)-induced EMT in LUSC. Results Immunohistochemistry of human tissue microarrays containing 90 pairs of adjacent and cancerous tissues revealed that CISD2 is considerably overexpressed in LUSC and strongly linked to poor OS. Functional experiments suggested that silencing endogenous CISD2 inhibited the growth, colony formation, migration, and invasion of H2170 and H226 cell lines. Exogenous overexpression of CISD2 facilitated these phenotypes in SK-MES-1 and H2170 cells. Furthermore, CISD2 promoted EMT progression by increasing the expression of mesenchymal markers (N-cadherin, vimentin, Snail, and Slug) as well as SMAD2/3 and reducing the expression of the epithelial marker E-cadherin. Mechanistically, our studies provide the first evidence that CISD2 can promote EMT by enhancing TGF-β1-induced Smad2/3 expression in LUSC cells (AU)

DNA oxidative damage in oral cancer: 8-hydroxy-2´-deoxyguanosine immunoexpression assessment

Background: The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´- deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication. Material and Methods: We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of followup. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus. Results: Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value ≤ 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001). Conclusions: All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death. (AU)

Combinación de colagenasa y ácido hialurónico en el abordaje de lesión por radiodermitis de Grado IV en carcinoma escamoso / Combination of collagenase and hyaluronic acid in the approach to grade IV radiodermitis lesion in squamous cell carcinoma

El carcinoma de células escamosas (CCE) de la piel es la segunda forma más frecuente de cáncer de piel, caracterizado por el crecimiento anormal y acelerado de las células escamosas. Detectado a tiempo, la mayoría de los CCE se pueden curar. Puede aparecer como manchas rojas escamosas, llagas abiertas, piel áspera, engrosada o verrugosa, o crecimientos elevados con una depresión en el medio y puede formar costras, picar o sangrar y suele ser más habitual en zonas expuestas al sol. La radiodermitis es un problema habitual en personas que reciben radioterapia como tratamiento para el cáncer, apareciendo en más del 95% de los casos. La intensidad de la reacción depende del tipo de radiación, la dosis total y la dosis de fracción, el área afectada, latécnica de tratamiento, la administración simultánea de quimioterápicos, además de factores del propio individuo (enfermedades crónicas, tabaquismo, estado nutricional, etc.). Con este caso, nos disponemos a demostrar la eficacia de la combinación de colagenasa bacteriana y ácido hialurónico como un óptimo procedimiento para el abordaje de este tipo de lesiones. El uso de este producto en nuestra consulta en pacientes con diferentes etiologías y como procedimiento para el abordaje de preparación del lecho de la herida (PLH), nos animó a comprobar su eficacia en lesiones de estas características. (AU)

Squamous cell carcinoma (SCC) of the skin is the second most common form of skin cancer, characterized by the abnormal and accelerated growth of squamous cells. Detected early, most SCC can be healed. It may appear as red scaly patches, open sores, rough, thickened or warty skin, or raised growths with a depression in the middle and may crust, itch or bleed and is more common in sun-exposed areas. Radiodermitis is a common problem in people receiving radiationtherapy as a cancer treatment, occurring in more than 95% of cases. The intensity of the reaction depends on the type of radiation, the total dose and the fraction dose, the affected area, the treatment technique, the simultaneous administration of chemotherapy, as well as individual factors (chronic diseases, smoking, nutritional status, etc.). With this case, we will demonstrate the efficacy of the combination of bacterial collagenase and hyaluronic acid as an optimal procedure for the treatment of this type of wounds. The use of this product in our practice in patients with different etiologies and as a procedure for the wound bed preparation approach encouraged us to prove its efficacy in wounds of these characteristics. (AU)

The development of radioresistant oral squamous carcinoma cell lines and identification of radiotherapy-related biomarkers

Background In the treatment of oral squamous cell carcinoma (OSCC), radiation resistance remains an important obstacle to patient outcomes. Progress in understanding the molecular mechanisms of radioresistance has been limited by research models that do not fully recapitulate the biological features of solid tumors. In this study, we aimed to develop novel in vitro models to investigate the underlying basis of radioresistance in OSCC and to identify novel biomarkers. Methods Parental OSCC cells (SCC9 and CAL27) were repeatedly exposed to ionizing radiation to develop isogenic radioresistant cell lines. We characterized the phenotypic differences between the parental and radioresistant cell lines. RNA sequencing was used to identify differentially expressed genes (DEGs), and bioinformatics analysis identified candidate molecules that may be related to OSCC radiotherapy. Results Two isogenic radioresistant cell lines for OSCC were successfully established. The radioresistant cells displayed a radioresistant phenotype when compared to the parental cells. Two hundred and sixty DEGs were co-expressed in SCC9-RR and CAL27-RR, and thirty-eight DEGs were upregulated or downregulated in both cell lines. The associations between the overall survival (OS) of OSCC patients and the identified genes were analyzed using data from the Cancer Genome Atlas (TCGA) database. A total of six candidate genes (KCNJ2, CLEC18C, P3H3, PIK3R3, SERPINE1, and TMC8) were closely associated with prognosis. Conclusion This study demonstrated the utility of constructing isogenic cell models to investigate the molecular changes associated with radioresistance. Six genes were identified based on the data from the radioresistant cells that may be potential targets in the treatment of OSCC (AU)

Immunohistochemical expression of COX-2, Ki-67, Bcl-2, Bax, VEGF and CD105 according to histological grading in oral squamous cell carcinoma / Expresión inmunohistoquímica de COX-2, Ki-67, Bcl-2, Bax, VEGF y CD105 según el grado histológico en el carcinoma oral de células escamosas

Introduction: Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck cancer. Few studies have analyzed the expression of proteins related to inflammation (COX-2) and tumor progression according to the histological grade of OSCC. Objective: Analyze the immunohistochemical expression of COX-2, Ki-67 (cell proliferation), Bcl-2/Bax (apoptosis), VEGF, and CD105 (angiogenesis) according to histological grades of OSCC.Material and methodsThe immunohistochemical expression of COX-2, Ki-67, Bcl-2, Bax, VEGF, and CD105 of 58 cases of OSCC was analyzed. 13 cases of oral mucosa (OM) were analyzed as controls. Results: COX-2, VEGF, CD105, and Ki-67 were higher in OSCC than in OM, particularly in poorly differentiated OSCC (p<0.05). Bax expression was lower in poorly differentiated OSCC (p<0.001). The Bcl-2/Bax ratio was higher in OSCC compared to MO (p<0.05). Conclusion: There are immunohistochemical differences according to histological grades of OSCC, which could influence clinical behavior.(AU)

Introducción: El carcinoma oral de células escamosas (COCE) es el cáncer de cabeza y cuello más prevalente. Escasos estudios analizan la expresión de proteínas relacionadas a inflamación (COX-2) y progresión tumoral según el grado histológico de COCE. Objetivo: Analizar la expresión inmunohistoquímica de COX-2, Ki-67 (proliferación celular), Bcl-2/Bax (apoptosis), VEGF y CD105 (angiogénesis) según grados histológicos de COCE.Material y métodos. Se analizó la expresión inmunohistoquímica de COX-2, Ki-67, Bcl-2, Bax, VEGF y CD105 de 58 casos de COCE. Trece casos de mucosa oral (MO) fueron analizados como control. Resultados: Las expresiones de COX-2, VEGF, CD105 y Ki-67 fueron mayores en el COCE comparadas con la MO, particularmente en el COCE pobremente diferenciado (p < 0,05). La expresión de Bax fue menor en el COCE pobremente diferenciado (p < 0,001). La razón Bcl-2/Bax fue mayor en COCE comparado con MO (p < 0,05). Conclusión: Existen diferencias inmunohistoquímicas según grados histológicos de COCE, lo que podría determinar una evolución clínica diferenciada.(AU)

The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma

Background: Oral squamous cell carcinoma (OSCC) has high morbidity and mortality rates while oral verrucous carcinoma (OVC), an uncommon variant of OSCC, exhibits a distinct biological behavior. CLIC4 protein plays a role in the cell cycle and apoptosis regulation and participates in the myofibroblasts transdifferentiation process, which are the main cells of the tumor stroma. This study analyzed the immunoexpression of CLIC4 and α-SMA in 20 OSCC cases and 15 OVC cases. Material and methods: A semiquantitative analysis of CLIC4 and α-SMA immunoexpression was performed in the parenchyma and stroma. Nuclear and cytoplasmic reactivity was analyzed separately for the CLIC4 immunostaining. The data were submitted to Pearson's chi-square and Spearman's correlation tests (p ≤ 0.05). Results: In the CLIC4 analysis, there was a significant difference in the immunoexpression of this protein between OSCC and OVC stroma (p < 0.001). It was observed a higher expression of α-SMA in the OSCC stroma. There was a positive and significant correlation between CLIC4 and α-SMA immunoexpression in the OVC stroma (r = 0,612; p = 0,015). Conclusions: The decrease or absence of nuclear CLIC4 immunoexpression in the neoplastic epithelial cells and the increase of its expression in the stroma may influence the difference in biological behavior between OSCC and OVC. (AU)