Differentiation Of Squamous Cell Carcinoma Research Articles

Expression Analysis of Retinal G Protein-coupled Receptor and its Correlation with Regulation of the Balance between Proliferation and Aberrant Differentiation in Cutaneous Squamous Cell Carcinoma.

Retinal G protein-coupled receptor (RGR), a photosensitive protein, functions as a retinal photoisomerase under light conditions in humans. Cutaneous squamous cell carcinoma (cSCC) is linked to chronic ultraviolet exposure, which suggests that the photoreceptor RGR may be associated with tumorigenesis and progression of squamous cell carcinoma (SCC). However, the expression and function of RGR remain uncharacterized in SCC. This study analysed RGR expression in normal skin and in lesions of actinic keratosis, Bowen's disease and invasive SCC of the skin with respect to SCC initiation and development. A total of 237 samples (normal skin (n = 28), actinic keratosis (n = 42), Bowen's (n = 35) and invasive SCC (n = 132) lesions) were examined using immunohistochemistry. Invasive SCC samples had higher expression of RGR protein than the other samples. A high immunohistochemical score for RGR was associated with increased tumour size, tumour depth, Clark level, factor classification, and degree of differentiation and a more aggressive histological subtype. In addition, RGR expression was inversely correlated with involucrin expression and positively correlated with proliferating cell nuclear antigen (PCNA) and Ki67 expression. Furthermore, RGR regulates SCC cell differentiation through the PI3K-Akt signalling pathway, as determined using molecular biology approaches in vitro, suggesting that high expression of RGR is associated with aberrant proliferation and differentiation in SCC.

Texture analysis using short-tau inversion recovery magnetic resonance images to differentiate squamous cell carcinoma of the gingiva from medication-related osteonecrosis of the jaw.

Despite the difficulty in distinguishing between squamous cell carcinoma (SCC) and medication-related osteonecrosis of the jaw (MRONJ) on the basis of medical imaging examinations, the two conditions have completely different treatment methods and prognoses. Therefore, differentiation of SCC from MRONJ on imaging examinations is very important. This study aimed to distinguish SCC from MRONJ by performing texture analysis using magnetic resonance imaging (MRI) short-tau inversion recovery images. This retrospective case-control study included 14 patients with SCC of the lower gingiva and 35 with MRONJ of the mandible who underwent MRI and computed tomography (CT) for suspected SCC or MRONJ. SCC was identified by histopathological examination of tissues excised during surgery. The radiomics features of SCC and MRONJ were analyzed using the open-access software MaZda version 3.3 (Technical University of Lodz, Institute of Electronics, Poland). CT was used to evaluate the presence or absence of qualitative findings (sclerosis, sequestrum, osteolysis, periosteal reaction, and cellulitis) of SCC and MRONJ. Among the 19 texture features selected using MaZda feature-reduction methods, SCC of the gingiva and MRONJ of the mandible revealed differences in two histogram features, one absolute gradient feature, and 16Gy level co-occurrence matrix features. In particular, the percentile, angular second moment, entropy, and difference entropy exhibited excellent diagnostic performance. Non-contrast-enhanced MRI texture analysis revealed differences in texture parameters between mandibular SCC and mandibular MRONJ. MRI texture analysis can be a new noninvasive quantitative method for distinguishing between SCC and MRONJ.

MicroRNA Expression Profile Separates Squamous Cell Carcinoma by Mode of Differentiation.

Squamous cell carcinoma (SCC) is a non-melanoma skin cancer with several risk factors including age and sun exposure. The degree of histological differentiation is considered an independent predictor of recurrence, metastasis, and survival. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in regulating gene expression, culminating in the initiation and progression of multiple tumors. The aim of this study was to determine changes in miRNA expression as a result of the mode of differentiation in SCC. We analyzed 29 SCC samples that were separated by mode of differentiation into well (n=4), moderate (n=20) and poor (n=5). Of the 29 samples, five had matched normal tissues, which were used as controls. Total RNA was extracted using the RNeasy FFPE kit, and miRNAs were quantified using Qiagen MiRCURY LNA miRNA PCR Assays. Ten miRNAs (hsa-miR-21, hsa-miR-146b-3p, hsa-miR-155-5p, hsa-miR-451a, hsa-miR-196-5p, hsa-miR-221-5p, hsa-miR-375, hsa-miR-205-5p, hsa-let-7d-5p and hsa-miR-491-5p) that have been previously differentiated in cancer, were quantified. A fold regulation above 1 indicated upregulation and below 1, downregulation. Hierarchical clustering showed that the miRNA expression profile in the moderately differentiated group was similar to the well-differentiated group. The miRNA with the greatest upregulation in the moderate group was hsa-miR-375, while in the well group, hsa-miR-491-5p showed the greatest downregulation. In conclusion, this study observed that the well and moderate groups had similar microRNA expression patterns compared to the poorly differentiated group. MicroRNA expression profiling may be used to better understand the factors underpinning mode of differentiation in SCC.

Agreement Between Mucicarmine-Stained Bronchial Brushing and Bronchial Biopsy in Subtyping Non-small Cell Lung Carcinoma.

Background Bronchial brushing and biopsy are used for the diagnosis of lung carcinoma as most of these tumors are unresectable. Recently, the subclassification of non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC) and squamous cell carcinoma (SCC) has become mandatory due to the emergence of targeted therapies. Due to the inherent limitations of small samples, subcategorization of a tumor is not always possible. Immunohistochemical and mucin stains are being used for this purpose, especially for tumors with poorly differentiated features. In our study, we utilized mucicarmine mucin stain to refine the differentiation of SCC and ADC on bronchial brushing and determine its agreement with bronchial biopsy. This study aimed to measure the degree of agreement between mucicarmine-stained bronchial brushing and bronchial biopsy for subtyping NSCLC into SCC and ADC. Methodology This descriptive, cross-sectional study was conducted in the pathology department of Allama Iqbal Medical College. Samples were collected by the pulmonology department of Jinnah Hospital Lahore. The study was conducted for 10 months from June 2020 to April 2021. A total of 60 cases diagnosed as NSCLC, aged between 35 and 80 years, were included in this study. After cytohistological evaluation of bronchial brushing and bronchial biopsy specimens, the agreement was deduced using kappa statistics. Results The strength of agreement between mucicarmine-stained bronchial brushing and bronchial biopsy for subtyping NSCLC into SCC and ADC was found to be substantial. Conclusions As significant agreement exists between the two modalities, mucicarmine-stained bronchial brushing can be used for a reliable and rapid categorization of NSCLC.

Histological Variants of Squamous and Basal Cell Carcinoma in Squamates and Chelonians: A Comprehensive Classification.

In the present study, the histological characteristics of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) obtained from 22 squamate and 13 chelonian species were retrospectively evaluated. While the examined tissues were originally diagnosed as 28 SCCs and 7 BCCs based on histological evaluation by a specialty diagnostic service, eight SCCs could be re-classified as BCCs and three SCCs proved to be non-neoplastic lesions. In addition, all SCCs and BCCs were classified into distinct histological variants. The SCCs could be categorized as one SCC in situ, three moderately differentiated SCCs, seven well-differentiated SCCs, and six keratoacanthomas. BCCs were classified as five solid BCCs, four infiltrating BCCs, five keratotic BCCs, and one basosquamous cell carcinoma. In addition, the present study reports the occurrence of BCCs in seven reptile species for the first time. In contrast to what has been documented in humans, IHC staining with the commercially available epithelial membrane antigen and epithelial antigen clone Ber-EP4 does not allow differentiation of SCCs from BCCs in reptiles, while cyclooxygenase-2 and E-cadherin staining seem to have discriminating potential. Although the gross pathological features of the examined SCCs and BCCs were highly similar, each tumor could be unequivocally assigned to a distinct histological variant according to the observed histological characteristics. Based on the results of this study, a histopathological classification for SCCs and BCCs is proposed, allowing accurate identification and differentiation of SCCs and BCCs and their histological variants in the examined reptile species. Presumably, BCCs are severely underdiagnosed in squamates and chelonians.

RETROSPECTIVE ANALYSIS OF MALIGNANT ORAL INJURIES DIAGNOSED IN A DENTAL SPECIALTY CENTER

<h3>Objectives</h3> To carry out a retrospective analysis of the prevalence of malignant oral lesions in a dental specialties center. <h3>Study Design</h3> A retrospective quantitative study of patients seen in the stomatology sector from 2010 to 2019. <h3>Results</h3> In this period, 818 biopsies were performed, with 706 cases of benign lesions, 58 potentially malignant oral lesions, and 54 malignant lesions. Of the patients diagnosed with malignant oral lesions, males were more affected (77.78%), the predominant age group was over age 50 years, and the most prevalent anatomic site was the tongue (29, 63%), followed by the lower lip (22, 22%). Regarding habits, 72.22% were smokers and 5.56% used tobacco and alcohol. Among the lesions, the prevalence of squamous cell carcinoma (SCC) was 88.89%, carcinoma in situ and basal cell 3.70%, and mucoepidermoid and leiomyosarcoma carcinoma 1.85%. Regarding the histopathologic changes in the differentiation of SCC, 48.15% were differentiated, 31.48% were well differentiated, and 9.26% were poorly differentiated. <h3>Conclusions</h3> This research agrees with the studies already published, finding a higher prevalence of malignant lesions in men over 40 years old, with SCC in the tongue being the most common and associated with risk factors such as smoking.

A CT-based radiomics nomogram for differentiation of squamous cell carcinoma and non-Hodgkin's lymphoma of the palatine tonsil.

Accurate preoperative differentiation between squamous cell carcinoma (SCC) and non-Hodgkin's lymphoma (NHL) in the palatine tonsil is crucial because of their different treatment. This study aimed to construct and validate a contrast-enhanced CT (CECT)-based radiomics nomogram for preoperative differentiation of SCC and NHL in the palatine tonsil. This study enrolled 135 patients with a pathological diagnosis of SCC or NHL from two clinical centers, who were divided into training (n = 94; SCC = 50, NHL = 44) and external validation sets (n = 41; SCC = 22, NHL = 19). A radiomics signature was constructed from radiomics features extracted from routine CECT images and a radiomics score (Rad-score) was calculated. A clinical model was established using demographic features and CT findings. The independent clinical factors and Rad-score were combined to construct a radiomics nomogram. Performance of the clinical model, radiomics signature, and nomogram was assessed using receiver operating characteristics analysis and decision curve analysis. Eleven features were finally selected to construct the radiomics signature. The radiomics nomogram incorporating gender, mean CECT value, and radiomics signature showed better predictive value for differentiating SCC from NHL than the clinical model for training (AUC, 0.919 vs. 0.801, p = 0.004) and validation (AUC, 0.876 vs. 0.703, p = 0.029) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model. A CECT-based radiomics nomogram was constructed incorporating gender, mean CECT value, and radiomics signature. This nomogram showed favorable predictive efficacy for differentiating SCC from NHL in the palatine tonsil, and might be useful for clinical decision-making. • Differential diagnosis between SCC and NHL in the palatine tonsil is difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, gender, and mean contrast-enhanced CT value facilitates differentiation of SCC from NHL with improved diagnostic efficacy.

Texture Indices of 18F-FDG PET/CT for Differentiating Squamous Cell Carcinoma and Non-Hodgkin's Lymphoma of the Oropharynx.

We assessed the role of 18F-FDG PET/CT texture indices for the differentiation of squamous cell carcinoma (SCC) and non-Hodgkin's lymphoma (NHL) in the oropharynx. 18F-FDG PET/CT data for 27 patients with SCC and 25 patients with NHL in the oropharynx were investigated. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and six texture indices (homogeneity, entropy, short-run emphasis, long-run emphasis, low gray-level zone emphasis [LGZE], and high graylevel zone emphasis [HGZE]) were derived from PET images. PET/CT parameters of the SCC patients were compared with those of the NHL patients. The diagnostic accuracy of the indices for differentiating SCC from NHL was calculated by a receiver operating characteristic curve analysis. 18F-FDG uptake in the oropharynx was observed in all of the patients. The SUVmax, MTV, and TLG did not differ significantly between the SCC and NHL groups, but two of the six texture indices (LGZE [p=0.004] and HGZE [p=0.03]) showed significant differences between the groups. LGZE was the best discriminative index for the differentiation of SCC and NHL (55.6% sensitivity, 88.0% specificity). The LGZE and HGZE texture indices derived from 18F-FDG PET/CT images may be useful in differentiating SCC and NHL in the oropharynx.

Variations of P40 and P63 Immunostains in Different Grades of Esophageal Squamous Cell Carcinoma: A Potential Diagnostic Pitfall.

The distinction of esophageal squamous cell carcinoma (SCC) from adenocarcinoma (adenoCA) using targeted therapies has become critical for small biopsies. In the United States, esophageal SCC is relatively uncommon compared with AdenoCA, with only few detailed immunohistochemical (IHC) studies on esophageal SCC. We characterized p40 and p63 IHC across various grades of squamous differentiation in esophageal SCC and compared their sensitivities between esophageal SCC and adenoCA. Twenty-eight esophageal SCC and 26 esophageal adenoCA (control group) samples were stained for p40, p63, and CK5/6. All hematoxylin-and-eosin-stained SCC slides were reviewed. Tumors were graded according to the World Health Organization classification: well, moderately, or poorly differentiated (WD, MD, and PD, respectively). Considering morphological heterogeneity, individual differentiation components within the same tumor were scored separately (0% to 100%) according to the proportion of immunoreactive cells and marked as positive (≥5%) or negative (<5%). Among 28 esophageal SCC, 15 had mixed intratumoral differentiation. There were 16 WD, 19 MD, and 14 PD components. P40 immunoreactivity was significantly lower in WD than in MD or PD components (P<0.001), P63 immunoreactivity patterns were similar (P<0.001), while CK5/6 showed no differences (P>0.05). The sensitivities for SCC components were 98% (P40), 100% (P63), and 100% (CK5/6), while those for esophageal AdenoCA were significantly lower: 4% (P40), 4% (P63), and 8% (CK5/6). P40 and P63 were sensitive and specific for routine esophageal SCC diagnosis. However, their immunostaining was significantly lower in WD SCC than in higher grade tumors. IHC results for small biopsy specimens should be interpreted carefully, particularly in WD components.

Minimalistic Immunomarker Approach for the Diagnosis of Non Small Cell Lung Carcinoma with Emphasis on Tumours with Ambiguous Morphology

Introduction: Diagnosing Non Small Cell Lung Carcinoma (NSCLC) by morphology on small biopsy specimens are on demand. With major advances in molecular testing of lung cancers and introduction of targeted therapies, accurate subtyping of NSCLC has become essential. Immunophenotyping with various immunomarkers is helpful in identification of different tumour subtypes. As sparing material for molecular testing is mandatory, a minimalistic Immunohistochemistry (IHC) based diagnostic approach is warranted by means of reliable and accessible immunomarkers. In this study, one immunomarker Thyroid Transcription Factor (TTF1) for glandular and protein40 (p40) for squamous differentiation was applied to maximise the proportion of accurately subtyped NSCLC on small biopsy specimens. Aim: To find utility of TTF1/p40 minimalistic immunopanel in subtyping NSCLC especially those with ambiguous morphology. Materials and Methods: This retrospective observational study was conducted from 15 December 2020 to 5 March 2021 in a tertiary care hospital in which 93 (mean age 64.8 years, Male:female ratio 4.8:1) consecutive lung biopsies from suspected lung carcinoma obtained from January 2019 to December 2020 were studied. The morphological diagnosis and diagnosis after application of TTF1 and p40 minimalistic immunopanel was evaluated using chi-square test. The p-value &lt;0.01 was considered significant. Results: Based on morphology, only 21 (22.5%) cases out of 93 cases of NSCLC were characterised into Adenocarcinoma (ADC) and Squamous Cell Carcinoma (SCC), whereas 72 (77.4%) were grouped as NSCLC ambiguous type. With addition of IHC (p40 and TTF1), the latter category reduced to 10 (10.7%) which constituted final NSCLC Not Otherwise Specified (NOS) category and a sum of 79 (84.9%) cases were accurately subtyped into SCC and ADC. Significance of adding TTF1/p40 immunopanel in the diagnosis of non small cell carcinoma was found to be very significant(p-value&lt;0.001) p40 showed 100% sensitivity and 92.6% specificity for SCC where as TTF1 showed sensitivity of 92.59% and 100% specificity for ADC. Conclusion: Study showed that a minimalistic approach using only two antibodies (p40 and TTF1) might help in subtyping NSCLC especially those with ambiguous morphology and reduction of category of NSCLC NOS significantly and contribute in sparing material for molecular testing.

Comparison of Imaging Findings between Human Papillomavirus-positive and -Negative Squamous Cell Carcinomas of the Maxillary Sinus.

Objectives:This study aimed to assess the efficacy of imaging findings when differentiating between human papillomavirus (HPV)-positive and -negative squamous cell carcinomas (SCCs) of the maxillary sinus.Material and Methods:This study included 37 patients with histopathologically and immunohistochemically confirmed SCCs of the maxillary sinus (three HPV positive and 34 HPV negative). Apparent diffusion coefficients (ADCs), MR signal intensities, CT findings, and maximum standardized uptake (SUVmax) were correlated with the two pathologies.Results:The minimum ADC (ADCmin) was significantly lower in HPV-positive SCCs than in HPV-negative SCCs (0.50 ± 0.02 vs. 0.70 ± 0.13 × 10−3 mm2/s, P < 0.01). The mean ADC (ADCmean) was not significantly different between HPV-positive SCCs and HPV-negative SCCs (0.84 ± 0.07 vs. 0.97 ± 0.18 ×10−3 mm2/s, P = 0.18). The areas under the receiver operating characteristic curves for ADCmin and ADCmean were 0.986 (P < 0.01) and 0.754 (P < 0.05), respectively. The sensitivity and specificity, with a threshold of ADCmin (0.516 × 10−3 mm2/s) for a diagnosis of HPV-positive SCCs, were 100% and 96%, respectively. However, no significant differences were observed in MR signal intensities, CT findings, and SUVmax between HPV-positive and HPV-negative SCCs.Conclusion:ADCmin is a useful parameter for the differentiation of HPV-positive and HPV-negative SCCs of the maxillary sinus.

Altered Coagulation Pattern in Different Histological Grades of Squamous Cell Carcinoma

Background: The incidence of squamous cell carcinoma has doubled in the last three decades associated with a high rate of morbidity and mortality. The incidence of bleeding and/or thrombosis in advanced stage cancer necessitates a need for research in blood coagulation abnormalities in malignancy. The objective of the present study was to determine the alteration in coagulation pattern among patients diagnosed with squamous cell carcinoma (SCC).&#x0D; Material and Methods: This cross-sectional study was conducted in Pathology department of Isra University Hospital, Hyderabad over a period of 06 months. A total of 126 samples were selected through non-probability convenient sampling. Both male and female patients of all age groups having SCC of skin, gastrointestinal and genital tract were included. The coagulation profile was analyzed by Sysmax CA 50 and Nycocard reader II. Data was entered into SPSS version 22.0 and results were analyzed.&#x0D; Results: The mean age of the patients with SCC in the present study was 55.5 ± 12 years with more male patients (n=81; 64.3%) as compared to females (n=45; 35.7%). Oral SCC was found to be the most common site of squamous cell carcinoma (43.7%). Majority of the patients had well differentiated SCC (42.1%) followed by moderately differentiated (40.5%) and poorly differentiated SCC (17.4%). The comparison of severity of SCC with coagulation profile revealed that PT (P=0.01), APTT (P=0.001), D-dimers (P=0.01 and TT (P=0.01) were significantly increased, whereas fibrinogen was significantly decreased (P=0.001).&#x0D; Conclusions: The histological differentiation of SCC (from well differentiated to poorly differentiated tumors) showed a highly significant association with different coagulation profile parameters like PT, APTT, BT, CT, D-dimer, TT, and fibrinogen levels.

Greater specificity of p40 compared with p63 in distinguishing squamous cell carcinoma from adenocarcinoma in effusion cellblocks.

Objective:Squamous cell carcinoma (SCC) rarely causes malignant effusions. Distinguishing between SCC and adenocarcinoma in effusion cytology can be a challenge. p63 and p40 have been frequently used to support squamous cell differentiation in both histological and cytological specimens. However, similar results in cytological preparations of effusion fluids have been rarely reported. This study was designed to assess the diagnostic value of p63 and p40 immunoreactivity for the differentiation of SCC from adenocarcinoma in malignant effusions.Materials and Methods:Immunocytochemical staining of p63 and p40 was performed on thirty cellblock specimens, including ten malignant effusions carrying SCC and twenty malignant effusions showing adenocarcinoma. Any degree of nuclear staining was considered positive.Results:Of the ten SCC cases, 100% tested positive for both p63 and p40, and most cases showed diffuse staining (>25% of tumor cells). The expression of p63 and p40 was detected in 4 (20%) and 2 (10%) of twenty adenocarcinoma cases, and the extent of staining was all focal (≤25% of tumor cells). The p63 reactivity showed 100% sensitivity, 80% specificity, 71% positive predictive value, and 100% negative predictive value for the differentiation of SCC from adenocarcinoma in malignant effusions. The sensitivity of p40 for SCC was 100%, the specificity was 90%, the positive predictive value was 83%, and the negative predictive value was 100%.Conclusion:Although p63 and p40 are both useful markers for the diagnosis of SCC in malignant effusions, p40 is more specific than p63 in distinguishing SCC from adenocarcinoma.

LncRNA-MALAT1 is a promising biomarker for prognostic evaluation of tongue squamous cell carcinoma.

MALAT1 is recognized as an oncogenic lncRNA in various malignancies. Here, the authors aim to explore the association of MALAT1 expression and prognostic implication in tongue squamous cell carcinoma (SCC). The tongue tissues of 128 tongue SCC cases satisfying strict follow-up criteria and 28 normal cases were subjected to qRT-PCR assay for monitoring MALAT1 expression. Chi-square test was applied to explore the correlation between MALAT1 expression and clinicopathological features of tongue SCC. Kaplan-Meier analysis was used to calculate survival rates. Cox proportional hazard analysis was adopted to analyze the relationship between prognostic factors and patient survival. The expression of MALAT1 was upregulated in tongue SCC, compared to normal tongue tissues. The expression level of MALAT1 was correlated to differentiation and stage of tongue SCC, and high MALAT1 expression was associated with low disease-free survival and overall survival rates. Moreover, advanced tongue SCC patients with high MALAT1 level had lower disease-free survival and decreased overall survival rate than patients with low MALAT1 level. These results revealed that MALAT1 overexpression can be considered as a significant prognostic factor to independently predict the disease-free survival and overall survival rate of tongue SCC. The expression level of MALAT1 is closely related with progression of tongue SCC. Furthermore, MALAT1 can serve as an independent biomarker for prognostic evaluation of tongue SCC.

A survey of tumors affecting cattle, buffaloes and sheep, in El-Dakahlyia Governorate

In a 2-year survey of tumors occurring in ruminants reared in El-Dakahlyia Governorate, Egypt during the period from October 2016 to October 2018. 66 tumor masses were collected: 60 from cattle, 2 from buffaloes and 4 from sheep. According to histopathology of cattle tumors, 15 neoplasms were diagnosed as cutaneous papilloma, 5 neoplasms were diagnosed as cutaneous fibropapillomas, 25 neoplasms were diagnosed as squamous-cell carcinoma (SCC) of the eye; 8 neoplasms were diagnosed as SCC of perineum, 1 neoplasm was diagnosed as SCC in skin of muzzle, 2 neoplasms were diagnosed as epulis in dental pad, 2 neoplasms were diagnosed as vaginal leiomyoma, 1 neoplasm was diagnosed as fibroma and 1 neoplasm was diagnosed as liposarcoma. Histopathology of buffalo tumors revealed SCC in head skin (1 case) and buccal cavity (1 case). Histopathology of sheep tumors revealed SCC in skin under the tail (2 cases), skin of groin (1 case) and skin of abdomen (1 case). In conclusion, cattle (60/66) were more susceptible to tumors than buffaloes (2/66) and sheep (4/66). Females accounted for a higher percentage of the neoplasms (47/66) than males (19/66). Adult animals aged above 2 years were more frequently affected than young. The occurrence of epithelial tumors (60/66) was greater than the mesenchymal tumors (6/66). The most common epithelial tumors were ocular SCC and cutaneous papilloma. Number of malignant tumors (41/66) was higher than number of benign tumors (25/66). Variable degrees of bovine SCC differentiation were detected. Meanwhile ovine SCC appeared only well differentiated.

Characteristics and Outcomes of Pancreatic Cancer by Histological Subtypes.

Except pancreatic adenocarcinoma, pancreatic cancer has several uncommon histological subtypes, including invasive intraductal papillary mucinous neoplasm (IPMN), pancreatic neuroendocrine tumor (pNET), adenosquamous carcinoma, invasive mucinous cystic neoplasm (MCN), acinar cell carcinoma (ACC), squamous cell carcinoma (SCC), and invasive solid pseudopapillary tumor (SPT). However, features of theses uncommon subtypes are not systematically analyzed. Subjects with different histological subtypes of pancreatic cancers were retrieved from the Surveillance, Epidemiology, and End Results registry. Characteristics and behaviors of uncommon subtypes were compared. Pancreatic adenocarcinoma (85.8%) represented most primary pancreatic cancers, and other subtypes were rare (14.2%). Features of uncommon subtypes included females with SPT and MCN, located at the pancreatic body/tail of pNET, SPT, and MCN; poor differentiation of adenosquamous carcinoma and SCC; and large size of MCN, SPT, ACC, and SCC. In addition, IPMN, pNET, MCN, ACC, and SPT were indolent. For indolent subtypes, patients with locoregional tumor had prominent prognosis compared with patients with distant disease, especially for invasive IPMN (median survival, localized, 30.0 months; regional, 11.0 months; distant, 4.0 months). The study systematically summarizes characteristics and behaviors of primary pancreatic cancer by histological subtypes, which can facilitate the management of pancreatic cancer.

A survey of tumors affecting cattle, buffaloes and sheep, in El-Dakahlyia Governorate

In a 2-year survey of tumors occurring in ruminants reared in El-Dakahlyia Governorate, Egypt during the period from October 2016 to October 2018. 66 tumor masses were collected: 60 from cattle, 2 from buffaloes and 4 from sheep. According to histopathology of cattle tumors, 15 neoplasms were diagnosed as cutaneous papilloma, 5 neoplasms were diagnosed as cutaneous fibropapillomas, 25 neoplasms were diagnosed as squamous-cell carcinoma (SCC) of the eye; 8 neoplasms were diagnosed as SCC of perineum, 1 neoplasm was diagnosed as SCC in skin of muzzle, 2 neoplasms were diagnosed as epulis in dental pad, 2 neoplasms were diagnosed as vaginal leiomyoma, 1 neoplasm was diagnosed as fibroma and 1 neoplasm was diagnosed as liposarcoma. Histopathology of buffalo tumors revealed SCC in head skin (1 case) and buccal cavity (1 case). Histopathology of sheep tumors revealed SCC in skin under the tail (2 cases), skin of groin (1 case) and skin of abdomen (1 case). In conclusion, cattle (60/66) were more susceptible to tumors than buffaloes (2/66) and sheep (4/66). Females accounted for a higher percentage of the neoplasms (47/66) than males (19/66). Adult animals aged above 2 years were more frequently affected than young. The occurrence of epithelial tumors (60/66) was greater than the mesenchymal tumors (6/66). The most common epithelial tumors were ocular SCC and cutaneous papilloma. Number of malignant tumors (41/66) was higher than number of benign tumors (25/66). Variable degrees of bovine SCC differentiation were detected. Meanwhile ovine SCC appeared only well differentiated.

157 Uncharacterized protein REDI is required for epidermal differentiation and suppression of cancer invasion

Cutaneous squamous cell carcinoma (SCC) often demonstrates loss of epidermal differentiation that is regulated by an ever-increasing number of genes. REDI (Regulator of Epidermal Differentiation and Invasion) is a previously uncharacterized protein that we show controls skin differentiation and functions as a tumor suppressor in SCC. We identified REDI in an RNAseq-based screen for uncharacterized open reading frames with opposite patterns of expression in human SCC and keratinocyte differentiation. REDI is necessary and sufficient for epidermal differentiation; CRISPR/Cas9-mediated depletion of REDI in organotypic human epidermal tissue attenuates differentiation, while enforcing REDI expression enhances it. Proximity-dependent biotin identification was performed in organotypic skin tissue to distill REDI’s interactors and highlighted calcyclin binding protein (CACYBP), a protein not previously implicated in epidermal differentiation. Depletion of CACYBP phenocopies REDI loss and reduces differentiation in human skin tissue. Whole transcriptome analysis confirms that REDI and CACYBP co-control a significant subset of genes involved in keratinization, skin differentiation and development. Given REDI downregulation in SCC and its deletion in 21 TCGA cancer types, we evaluated the impact of REDI gain- and loss-of-function in organotypic human skin tissue programmed to transform into invasive epidermal neoplasia. REDI deletion enhances the extent and depth of invasion of Ras-transformed keratinocytes across the basement membrane, while enforced expression of REDI profoundly blocks early tumor progression. In each case, expression of REDI and the proto-oncogene c-RET are negatively correlated. Efforts are underway to confirm whether pharmacologic inhibition of c-RET offsets the impacts of REDI deletion on neoplastic invasion. Drug repurposing to identify a REDI mimic highlights HDAC inhibitors and inhibitors of PI3K/Akt as potential therapeutic candidates.

Assessment of Density of Neovascularization in Lower Lip Squamous Cell Carcinoma in Relation To Neoplasm Differentiation Grade in Patients with and without Neck Lymph Nodes Metastasis.

BACKGROUND:Squamous cell carcinoma (SCC) of the lower lip is a relatively rare carcinoma, with the incidence of 1 to 2%, but it is the most common carcinoma in the oral cavity accounting for 25-30% of all malignant oral tumours.AIM:This study aimed to determine the role of neovascularisation in the process of tumour progression.METHODS:We analysed the surgical specimens obtained from 60 patients with squamous cell carcinoma (SCC) of the lower lip. The examined group consisted of 45 specimens of patients without metastasis and 15 specimens of patients with metastasis in the regional lymph nodes. Histopathological slides were immunohistochemically stained with an antibody against CD34 and by hematoxylin & eosin staining for routine histopathological examination.RESULTS:The results obtained showed a statistically significant difference in the density of neovascularisation between groups of the SCC with different grade of differentiation (Kruskal-Wallis test: H (2, N = 60) = 30.0943, p = 0.00001). Statistical analysis also showed a significant difference in the density of vascularisation of lower lip SCC between patients without metastasis and patients with neck metastasis (Mann-Whitney U test, p = 0.000198). Applying Pearson’s chi-square test, we found a highly significant statistical difference in grade of SCC differentiation in patients with and without neck metastasis (p = 0.0000).CONCLUSION:In conclusion, the density of neoangiogenesis is increased in tumours with poorer differentiation and in patients with neck metastasis. So, the density of neovascularisation of the primary lip SCC may predict the tumour progression.

Immunohistochemical expression of cytokeratin 14 and association with the extent of squamous differentiation in urothelial carcinoma

Objective Evaluation of the diagnostic utility of cytokeratin 14 (CK14) immunostaining for squamous differentiation in urothelial carcinoma (UC). Background UC with squamous differentiation usually presents at an advanced stage than pure UC. Moreover, increased extent of squamous differentiation in UC tends to be associated with poor survival. Sometimes, immunohistochemical marker may be needed for diagnosis of squamous differentiation in UC. Materials and methods This retrospective cross-sectional study included 58 cases of radical cystectomy and 16 cases of cystoscopic biopsy diagnosed with bladder cancer. The cases included 16 cases of squamous cell carcinoma (SCC), 26 of pure UC, 31 of UC with squamous differentiation, and one case of adenocarcinoma. They were subjected to immunohistochemical staining for CK14. CK14 expression and its association with some clinicopathologic parameters were evaluated. Results CK14 showed positive expression in 74.2% of UC with squamous differentiation, 19.2% of pure UC, and all cases of SCC. It showed sensitivity of 74% and specificity of 81% for detecting squamous differentiation in UC. Its expression has significant association with the extent of squamous differentiation in UC (P = 0.001), perineural invasion (P = 0.03), and grade of SCC (P = 0.0001). Conclusion CK14 is a specific and sensitive marker in diagnosis of SCC and squamous differentiation in UC, and its expression is associated with poor prognostic parameters in bladder cancer.