Features Of Squamous Cell Carcinoma Research Articles

ARID1A prevents squamous cell carcinoma initiation and chemoresistance by antagonizing pRb/E2F1/c-Myc-mediated cancer stemness.

Squamous cell carcinoma (SCC) is defined as a category of aggressive malignancies arising from the squamous epithelium of various organs. Resistance to chemotherapies is a common feature of SCCs, which leads to a poor prognosis among SCC patients. Recently, studies have illustrated the essential tumor suppressive role of ARID1A in several cancer types, but its role in SCCs remains unclear. Cancer stemness has been recognized as a main reason for tumorigenesis and is commonly correlated with chemoresistance, yet the relationship between ARID1A and cancer stemness remains unknown. In this study, we showed that Arid1a conditional knockout mice had a high incidence of SCCs occurring in the tongue and esophagus. ARID1A depletion promoted tumor initiation and cancer stemness in human SCC cells. Mechanistic studies revealed that ARID1A blocked the interaction between cyclin-dependent kinases (CDKs) and retinoblastoma protein (Rb), reducing the phosphorylation of Rb. Dephosphorylated Rb suppressed E2F1 activity and then suppressed cancer stemness by inactivating c-Myc. Furthermore, we showed that ARID1A depletion significantly increased the chemoresistance of SCC and that a CDK inhibitor exhibited a favorable effect on rescuing the chemoresistance caused by ARID1A loss. Collectively, our study showed that ARID1A inhibits the cancer stemness of SCCs by competing with CDKs to bind with Rb to inhibit the E2F1/c-Myc pathway.

FIRST REPORT OF SQUAMOUS CELL CARCINOMA IN AN OVINE HOOF

This paper describes, for the first time, the clinical and histopathological characteristics of squamous cell carcinoma (SCC) in the hoof of a two-year-old female native Iranian sheep. Physical examination of this uncommon case revealed a large, irregularly-shaped, dark-brown-to-blackish, cauliflower-like ulcerated mass in the coronary band of the hoof which had caused lameness and bleeding. On cut-section, a dark red ulcerated stiff mass was observed. In the histopathological investigation, the moderately-differentiated SCC revealed keratin pearls accumulated moderately in cytoplasm, as well as acellular ones, and a relatively dense fibrous stroma. The large tumor cells contained a small amount of eosinophilic cytoplasm and vesicular nuclei, and in some cases, they were slightly hyperchromatic. As well, in some areas, mitotic figures as well as diverse inflammatory cells infiltration were observed. To the best of our knowledge, this is the first paper reporting an incidence of SCC in an ovine hoof.

ANALYSIS OF EXPRESSION OF P63 AND CASPASE-3 AND THEIR PREDICTIVE VALUE IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF MAXILLARY SINUS

Introduction: Maxillary sinus cancer is a malignant neoplasm with a prevalence of 3 to 5% of tumors in the head and neck and less than 1% of all malignant neoplasms. The role of p63 and caspase-3 and their predictive value in squamous cell carcinoma of maxillary sinus (SCCMS) remains an underdeveloped and controversial issue that determined the relevance of the study. The aim: To analyze the relationship between the level of expression of p63 and caspase-3 and clinical and morphological characteristics of squamous cell carcinoma of maxillary sinus and to determine their prognostic significance as immunohistochemical markers of tumor progression (relapse and metastases). Materials and methods: A comprehensive investigation with immunohistochemical study of squamous cell carcinoma of maxillary sinus of 103 patients with maxillary sinus cancer II - IV stage (T2-4 N0-3 M0) of the second clinical group was conducted. Results: The moderate and high expression rate of caspase-3 in the overall sample was 50.49% and 16.50% respectively, and one third of cases (33.01%) was characterized by a weak reaction. In the group without metastases (p <0.001), moderate expression of the marker (56.25%) prevailed; in the SCCMS group with metastases it was (60.87%). The mean level of expression of p63 in the examined patients with squamous cell carcinoma of maxillary sinus was 46.0%. The number of p63-positive specimens was statistically significantly (p = 0.034) higher in the SCCMS group with metastases. In patients with the development of squamous cell carcinoma of maxilla on the background of papilloma, a significantly higher (p <0.001) mean level of p63 expression was only moderate (90.91%) and high (9.09%). Conclusions: There was observed a relatively strong associate of the increase in the expression of caspase-3 with SCCMS metastases (p <0.001) and no correlation of immunohistochemical reaction of this marker with relapses. There was determined that the probability of metastases at high expression level of p63 is higher than in tumors with low and moderate level of the oncoprotein (p = 0.003). Based on the level of expression of p63, it is possible to predict the likelihood of development of SCCMS with papillomas (p <0.001); and the development of relapses of squamous cell carcinoma of maxillary sinus (p <0.001).

Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background.

Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including 'pathway in cancer' and 'cell cycle'. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers.

Metabolic reprogramming and Notch activity distinguish between non-small cell lung cancer subtypes

BackgroundPrevious studies suggested that the metabolism is differently reprogrammed in the major subtypes of non-small cell lung cancer (NSCLC), squamous cell carcinomas (SCC) and adenocarcinomas (AdC). However, a comprehensive analysis of this differential metabolic reprogramming is lacking.MethodsPublicly available gene expression data from human lung cancer samples and cell lines were analysed. Stable isotope resolved metabolomics were performed on SCC and ADC tumours in human patients and in freshly resected tumour slices.ResultsAnalysis of multiple transcriptomics data from human samples identified a SCC-distinguishing enzyme gene signature. SCC tumours from patients infused with [U-13C]-glucose and SCC tissue slices incubated with stable isotope tracers demonstrated differential glucose and glutamine catabolism compared to AdCs or non-cancerous lung, confirming increased activity through pathways defined by the SCC metabolic gene signature. Furthermore, the upregulation of Notch target genes was a distinguishing feature of SCCs, which correlated with the metabolic signature. Notch and MYC-driven murine lung tumours recapitulated the SCC-distinguishing metabolic reprogramming. However, the differences between SCCs and AdCs disappear in established cell lines in 2D culture.ConclusionsOur data emphasise the importance of studying lung cancer metabolism in vivo. They also highlight potential targets for therapeutic intervention in SCC patients including differentially expressed enzymes that catalyse reactions in glycolysis, glutamine catabolism, serine, nucleotide and glutathione biosynthesis.

No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis

Objective: Microsatellite instability (MSI) and a defective mismatch repair (MMR) system were described as beneficial tumor features for response to immune checkpoint therapy (PD-1 blockade). Meanwhile, the FDA approved PD-1/PD-L1 inhibition treatment for any solid tumor showing MSI and/or defects in the MMR system. For squamous cell carcinoma (SCC) of the penis, no data on the frequency of MSI and altered MMR protein expression are available to date. Therefore, we investigated the MSI status and the expression of MMR proteins in a large cohort of penile SCCs. Methods: The MSI status of 105 archival formalin-fixed, paraffin-embedded penile SCCs was analyzed using the 5 markers of the NCI consensus panel for MIS testing (BAT25, 26, D2S123, D17S250, and D5S346), or, in cases without representative nontumorous tissue using a validated panel of 5 quasimonomorphic mononucleotide repeat markers (BAT 25, 26 and NR21, 24, 27). The expression of the MMR proteins MLH1, MSH2, MSH6, and PMS2 was analyzed using immunohistochemistry and a tissue microarray of a subset of penile SCCs from our cohort (n = 75). Results: Overall, in 96/105 cases, at least 4 microsatellite markers gave interpretable results. None of the cases showed MSI. Immunohistochemistry for MMR proteins was analyzable in 70/75 cases. All cases showed a regular expression of the MMR proteins. Conclusion: MSI and defects in MMR protein expression are not regular features of penile SCC and might not act as biomarkers for PD-1/PD-L1 blockade therapy in penile carcinoma.

Premalignant male genital dermatoses.

The spectrum of conditions affecting the penile skin is varied and ranges from simple, benign dermatoses to premalignant and malignant conditions. Anogenital malignancies and premalignancies are an important personal/public health problem due to their effects on individuals' physical, mental, and sexual health. Furthermore, due to their etiological association with human papillomavirus infection, anogenital malignancies, and premalignancies constitute an immense public health burden. Bowen's disease, Bowenoid papulosis, and erythroplasia of Queyrat are the most widely seen premalignancies of anogenital region and are all forms of squamous intraepithelial neoplasia. Histopathologically, these conditions share identical histologic features of squamous cell carcinoma in situ, but their clinical features differ. In this article, we explore the common precancerous states that can lead to penile carcinoma.

Overexpression of cytokeratin 17 in conjunctival intraepithelial neoplasia and squamous cell carcinoma

Background Conjunctival intraepithelial neoplasia (CIN) is a preinvasive lesion of the ocular surface epithelium that can progress to squamous cell carcinoma (SCC), which has the potential to invade the nearby tissues, leading to visual loss. Unfortunately, the exact mechanisms of CIN and SCC pathogenesis, remain largely unknown. Cytokeratin 17 (CK17) functions specially among keratins as an oncoprotein which has been overexpressed in several cancers. To date, studies about the expression pattern of CK17 in CIN and SCC are limited. Aim The aims were to examine the immunohistochemical expression of CK17 in different conjunctival specimens including morphologically normal conjunctiva, pterygium, CIN, and SCC, and correlate CK17 expression with the available clinicopathological features of CIN and SCC specimens. Materials and methods The authors immunohistochemically investigated CK17 expression in 73 conjunctival specimens (40 CIN, 15 SCC, 10 pterygium, and eight morphologically normal conjunctiva). Results Overexpression of CK17 was detected in CIN and SCC specimens. On the contrary, limited basal expression of CK17 was noted in pterygium specimens and most of the morphologically normal conjunctiva. Significant higher mean of CK17 expression was found in CIN than morphologically normal conjunctiva and pterygium specimens. Moreover, the mean of CK17 expression was significantly higher in SCC specimens than CIN. Insignificant difference was detected between CK17 expression and all the clinicopathological features in CIN and SCC. Conclusion The authors can suggest that CK17 plays a role in the pathogenesis of CIN and SCC, with a possible role of CK17 in differentiation between benign and malignant conjunctival lesions.

A review of 31 cases of Marjolin's ulcer on scalp: Is it necessary to preventively remove the scar?

We aimed to report the clinical features of squamous cell carcinoma (SCC) occurring on scalp scar tissue among a Chinese population, demonstrate its pathological progress, analyse the prognosis-related factors, and share our clinical experience of managing this rare disease in practice. A retrospective study was conducted at West China Hospital from January 2013 to January 2018 aiming to identify patients with a diagnosis of SCC or squamous atypical hyperplasia arising from scalp scars. Their medical records were reviewed, and related data were retrieved. Follow up was conducted, and informed consent was obtained by phone calls in June 2018. Of the 31 scalp Marjolin's ulcer (MU) patients, the average latency period and post-ulceration period were 42.9 years and 37.5 months, respectively. Among them, 30 patients (97%) were diagnosed with cancer more than 5 years after initial injury, and 25 patients (80.7%) experienced a pre-ulceration period longer than 20 years. A negative correlation between scalp MU's post-ulceration period and its pre-ulceration period was identified. Only burn scars caused post-ulceration periods of more than 24 months (7/19). Incomplete healing wounds experienced a significantly shorter latency period (P = 0.004) and longer post-ulceration period than others (P < 0.0001). However, the depth of tumour infiltration and complete tumour resection were the only two independent factors that significantly dictated patients' survival in this study. In conclusion, the scalp scaring tissue experienced a long-term stable period but would transform to malignancy rapidly and progressively once ulceration formed. The underlying malignant transformation mechanism remains unclear. Thus, we recommend scalp scarring tissue to be radically removed.

Clinicopathologic characteristics of secondary squamous cell carcinoma of head and neck in survivors of allogeneic hematopoietic stem cell transplantation for hematologic malignancies

The risk of late complications including secondary malignancies is increased in long-term survivors of allogeneic hematopoietic stem cell transplants (HSCT). There is limited literature on the biological behavior and clinical features of squamous cell carcinoma (SCC) of head and neck post-HSCT. We present the clinical and pathologic characteristics on six patients who were diagnosed with SCC while in remission following an allogeneic HSCT. Median follow-up was 8 years. Five patients (83%) developed SCC of tongue and one developed esophageal SCC. Five patients had oral chronic graft-versus-host disease (cGvHD). The conventional risk factors of alcohol, tobacco, and human papillomavirus were absent. The most common presenting finding was the new-onset focal oral pain and ulcerated plaques clinically indistinguishable from a flare of their oral cGvHD lesions. We demonstrated that the SCC in three patients was of donor origin.

Squamous cell carcinoma in the anophthalmic socket: a series of four cases with HPV-16 profiling

PurposeTo present the clinical and histological features of squamous cell carcinoma (SCC) in the anophthalmic socket in four adult patients, and to determine the presence of human papillomavirus infection (HPV).MethodsRetrospective...

Clinicopathological features of squamous cell carcinoma of the oral cavity and oropharynx in young patients

Our aim was to examine the clinicopathological features of squamous cell carcinoma (SCC) of the oral cavity and oropharynx in a group of young patients who were dignosed during a 15-year period (2000–2014). Patients’ clinical details, risk factors, and survival were obtained from medical records. Formalin-fixed, paraffin-embedded, tissue was tested for high-risk human papillomavirus (HPV). The results were compared with those of a matching group of older patients. We identified 91 patients who were younger than 45 years old, and the 50 youngest patients were studied in detail. The male:female ratio was 2:1, with more tumours located in the oral cavity than in the oropharynx (35 compared with 15). HPV-related SCC was restricted to the oropharynx. When matched for site, stage and HPV status, five-year overall survival was similar in young and matched older patients (log-rank test, p=0.515). Our findings suggest that young patients with oral SCC have a disease profile similar to that of older patients with the condition. It is plausible that prognostic information generally available for oral cancers is applicable to young patients with the disease.

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacyof immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.

Expression of Minichromosome Maintenance Proteins in Actinic Keratosis and Squamous Cell Carcinoma.

Minichromosome maintenance (MCM) proteins are a group of proteins involved in DNA replication and cell-cycle regulation. Because they are associated with DNA through G1 into S phase, MCM proteins are potentially specific indicators of cell proliferation that could be valuable markers of dysplasia, and preinvasive and invasive malignant tumors. To analyze MCM protein expression patterns in actinic keratosis (AK), Bowen disease (BD), and cutaneous squamous cell carcinoma (SCC), we performed immunohistochemical staining of MCM2, -5, and -7 on tissue microarray blocks from 91 AK, 50 BD, and 174 SCC samples. The distribution and semiquantitatively assessed number of positive cells were analyzed in relation to the type of the lesion and the SCC prognostic parameters (grade, diameter, and thickness). Basal expression of all 3 proteins was observed more frequently in AK, whereas the distribution in BD was predominantly diffuse (P<0.001). All 3 proteins showed peripheral distribution in most well-differentiated SCC and diffuse distribution in poorly differentiated tumors (P<0.001). Using the 50% cut-off value, there was a statistically significant difference among AK, BD, and SCC (P<0.001). In addition, all MCM proteins showed highly significant differences (P<0.001) between well-differentiated SCC and both moderately and poorly differentiated SCC. The diffuse distribution and 50% cut-off value of positive cells revealed statistically significant associations of all MCM proteins with SCC thicker than 6 mm. Our results suggest a role for MCM proteins in the progression of in situ keratinocytic lesions and their association with high-risk features in SCC.

Tongue Squamous Cell Carcinoma in a European Lynx (Lynx Lynx): Papillomavirus Infection and Histologic Analysis.

Oral squamous cell carcinoma (SCC) is a common finding in domestic and wild felids. Only two cases of oral SCC have been reported in Lynx species (Lynx rufus and Lynx canadensis), at mandibular and gingival sites. In this study, we describe the first report of tongue SCC in a 15 years old female European lynx (Lynx lynx), along with viral investigations. Necropsy and histological analysis were performed and the presence of papillomavirus (PV) infection was investigated by ultrastructural and molecular methods. The lardaceous mass at tongue level was histologically diagnosed as moderately differentiated SCC. Typical microscopical features of SCC were also found in the retropharyngeal lymph node and at the pulmonary level. Neither viral DNA by PCR, nor viral particles by transmission electron microscopy were found. Despite that PV infection is associated with Felidae, this work reports the first description of tongue SCC in Lynx species, but no evidence of PV infection, suggesting that PV may not be involved in development of SCC in bobcat species.

Clinical and pathological features of squamous cell carcinoma of the lip

Clinical and pathological features of squamous cell carcinoma of the lip

Nuclear Morphometry of Lung Squamous Cell Carcinomas in Cytologic Study.

Background: The nuclei of most cancer cells in histopathologic preparations differ from normal nuclei and vary individually in size, shape, and chromatin pattern. Although the cytologic characteristics of squamous cell carcinoma (SCC) of the lung have been described, quantification of the cytologic features has not been established.Methods: Cytologic investigations were performed on bronchial brushings or washings, or fine-needle aspirates. We analyzed the nuclear area (NA) of 50 tumor cells in 32 patients with SCC of the lung and 50 bronchial epithelial cells in 20 patients with no evidence of malignancy including inflammatory lesions.Results: The NA of tumor cells (102.4 ± 26.2 μm2) was significantly larger than that of bronchial epithelial cells (64.1 ± 16.9 μm2) (P = 0.001). The receiver operating characteristic (ROC) curve analysis showed that an NA cutoff level of 86 μm2 had a sensitivity of 75% and specificity of 88% to detect malignant components.Conclusion: We conducted quantitative analyses of NA in SCC using cytologic specimen, NA was a useful parameter for evaluation of differential diagnosis between SCC and non-malignancies even in cytologic specimens.

Morphological and immunohistochemical features of squamous cell carcinoma and the probability of its metastasis

Morphological and immunohistochemical features of squamous cell carcinoma and the probability of its metastasis

Observation of squamous cell carcinoma in a goat flock in Iran

Squamous cell carcinoma (SCC) is a tumor consisting of squamous epithelial cells. This tumor is relatively uncommon in goats. In this report, we discuss clinical, gross and histopathological features of SCC in six goats. The goats were referred to the veterinary clinic with a progressive ulcerative and hemorrhagic mass located in the perineal area. The vital signs (temperature, pulse rate, respiration rate) were normal. Biopsy specimens were taken and histopathological examinations were done. The tumor cells were large and had an abundant eosinophilic cytoplasm, ovoid nuclei with a prominent nucleolus. Keratin tonofibers and keratin pearls were also seen. The mitotic figures were moderate. The mass was found to be a moderately differentiated SCC. Ulceration with infiltration of neutrophils was observed on the surface of the tumors. The SCC tumors are uncommon in goats and have multi-factorial etiology. Age, ultraviolet (UV) light exposure, lack of epidermis pigmentation, and viruses may be involved in the presence of SCC.

EGFR with TKI-sensitive mutations in exon 19 is highly expressed and frequently detected in Chinese patients with lung squamous carcinoma.

Recently, tyrosine kinase inhibitors (TKIs) have been recommended as a first-line treatment for advanced non-small cell lung cancer (NSCLC), significantly improving the treatment outcomes of lung adenocarcinoma patients with the EGFR mutation. However, the application of TKIs for lung squamous cell carcinoma (SCC), the second largest pathological subtype of NSCLC, remains controversial because available data for the EGFR mutation profile and frequency in SCC patients are limited. In this study, 89 bronchoscopic–biopsy specimens from Chinese SCC male patients were assayed for EGFR exon 19 mutation, using improved polymerase chain reaction-denature gel gradient electrophoresis. EGFR exon 19 mutations were detected in 77 of 89 (86.5%) patients, and included six kinds of point mutations (11.6%) and two deletions (Del_747-751 [64.9%] and Del_746-751 [23.3%]). We found that the proportion of mutated EGFR varied from 0.98% to 100% in positive specimens and increased with the development of the disease. The difference of proportion between Stage IV patients and Stage II patients or Stage III patients was significant (P<0.001). These results provided valuable clues to explain the reason why patients harboring the same mutation responded distinctly to TKI treatment. Del_747-751 and Del_746-751 were the dominant mutations in the assayed SCC patients (76.4%), and both belong to the EGFR–TKI-sensitive mutation. Recently research demonstrated that Del_746-751 patients have better response to EGFR-TKI than Del_L747-751 patients. However, our study indicated that majority of SCC patients (55.5%) carried Del_ L747-751. We suggest that the unique clinic features of SCC should be further studied to reveal the mechanism of poorer treatment outcome of EGFR–TKI therapy, and that a better treatment plan and more specific, potent targeted drugs for lung SCC need to be developed.