scholarly journals Effects of electrochemotherapy with cisplatin and peritumoral IL-12 gene electrotransfer on canine mast cell tumors: a histopathologic and immunohistochemical study

2017 ◽  
Vol 51 (3) ◽  
pp. 286-294 ◽  
Author(s):  
Claudia Salvadori ◽  
Tanja Svara ◽  
Guido Rocchigiani ◽  
Francesca Millanta ◽  
Darja Pavlin ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Lymphocytes ◽  
Mhc Class Ii ◽  
Cellular Response ◽  
Histopathological Examination ◽  
Combined Treatment ◽  
Gene Electrotransfer ◽  
Neoplastic Cells ◽  
Ki 67 ◽  
Mast Cell Tumors

AbstractBackgroundThe study was aimed to characterize tumor response after combined treatment employing electrochemotherapy with IL-12 gene electrotransfer in dogs with spontaneous mast cell tumors (MCT).Materials and methodsEleven dogs with eleven MCTswere included in the study. Histological changes were investigated in biopsy specimens collected before the treatment (T0), and 4 (T1) and 8 weeks (T2) later. Cellular infiltrates were characterized immunohistochemically by using anti CD3, CD20, Foxp3 (Treg), CD68 and anti MHC-class II antibodies. Proliferation and anti-apoptotic activity of neoplastic cells were assessed using anti Ki-67 and Bcl-2 antibodies. Angiogenetic processes were investigated immunohistochemically by using anti Factor VIII and anti CD31 antibodies and micro vessel density quantification.ResultsHistopathological examination of samples at T0confirmed the diagnosis and the presence of scanty infiltrates consisted mainly of T-lymphocytes and macrophages. At T1and T2neoplastic cells were drastically reduced in 7/11 cases, small clusters of neoplastic cells were detected in 3/11 cases and 1/11 cases neoplastic cells were still evident. Proliferation activity of neoplastic cells was significantly reduced at T1and T2and expression of anti-apoptotic protein at T1. Microvessel density was drastically reduced in all samples after treatment. The number of T-lymphocytes increased at T1, although not significant, while Treg were significant higher at T1and macrophages at T2.ConclusionsThe combined electrochemotherapy and IL-12 gene electrotransfer effectively induced a cellular response against neoplastic cells characterized mainly by the recruitment of T-lymphocytes and macrophages and a fibrotic proliferation with reduction of microvessels.

scholarly journals Ancillary techniques on the evaluation of canine cutaneous mast cell tumors from Brazil

2016 ◽  
Vol 46 (10) ◽  
pp. 1804-1810 ◽  
Author(s):  
Mariana Martins Flores ◽  
Renata Dalcol Mazaro ◽  
Ingeborg Maria Langohr ◽  
Alma Roy ◽  
Keith Strother ◽  
...  
Keyword(s):  
Mast Cell ◽  
Pcr Amplification ◽  
The United States ◽  
Growth Fraction ◽  
Grading System ◽  
Low Grade ◽  
Ki 67 ◽  
Mast Cell Tumors ◽  
Cutaneous Mast Cell ◽  
Exon 11

ABSTRACT: The use of histologic classification by a 2-tier grading system only, immunohistochemistry (IHC) for KIT and Ki-67 and polymerase chain reaction (PCR) for internal tandem duplications (ITD) on exon 11 has improved the prognostication of canine cutaneous mast cell tumors (CCMTs) particularly in the United States. However, these techniques are not commonly used in most Brazilian laboratories. Likewise, no studies, to date, have investigated the occurrence of ITD in CCMTs from the country. Thus, this study tested the 2-tier grading system, the immunohistochemistry for KIT and Ki-67 and the PCR for exon 11 in a group of Brazilian CCMTs with the goal of investigating the applicability of these tests in a Brazilian laboratory. Of the 39 CCMTs, 69.2% (27/39) were identified as low-grade and 30.8% (12/39) as high-grade by a 2-tier grading system. All tumors had a KIT expression pattern II, and 30.6% (11/36) had a high growth fraction (Ki-67). PCR amplification was successful in four of the 11 tumors examined. Two of these (50%) were positive for ITD. This study highlights the importance of using auxiliary techniques in the CCMT evaluation, identifies limitations and confirms the applicability of these methods on a routine diagnostic basis in Brazil. Our results will help to improve the prognostication of CCMTs in Brazilian diagnostic laboratories, encouraging the use of supplementary methods.

scholarly journals Sebaceous Carcinoma of The Lip: Report of a Case and Literature Review.

2021 ◽  
Author(s):  
Mariateresa Ambrosino ◽  
pasquale somma ◽  
andrea santarelli ◽  
stefania staiabano ◽  
michele di cosola ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Histopathological Examination ◽  
Sebaceous Carcinoma ◽  
Neoplastic Tissue ◽  
Male Smoker ◽  
Neoplastic Cells ◽  
Ki 67 ◽  
Lower Lip ◽  
S 100

Abstract Background Sebaceous carcinoma (SC) is a very rare, aggressive, malignant tumor arising in the adnexal epithelium of the sebaceous gland. SC in the oral cavity is extremely rare, in literature there are only 14 cases. We reported the 4th case of sebaceous carcinoma involving the lip Case presentation A 71-year-old male smoker presented an ulcerated lesion in the lateral region of the lower lip. The patient stated that the lesion had been present for 1 year. The past medical history was unremarkable. Extra-oral examination revealed a markedly ulcerated, exophytic, irregularly shaped, indurated mass of the lower right labial region, measuring 1.8 cm in size. The nodular lesion, located at the point of transition between mucosa and skin, showed a central ulceration. No other intraoral lesions were identified. The clinical differential diagnosis included squamous cell carcinoma, basal cell carcinoma with sebaceous differentiation and salivary gland neoplasms. The operation was performed under local anaesthesia. On histopathological examination, the tumor was composed by nodules or sheet of cells separated by a fibrovascolar stroma. The neoplastic tissue was deeply infiltrating, involving the submucosa and even the underlying muscle. Neoplastic cells showed a range of sebaceous differentiation with finely vacuolated rather than clear cytoplasm. Neoplastic cells were positive for S-100 protein, EMA, but negative for CEA. Therefore, based on these findings, a diagnosis of sebaceous carcinoma of the lower lip was rendered. Conclusion The histogenesis, differential diagnosis, and clinicopathologic conditions of this disease in the literature were reviewed. SC should be distinguished from other tumors full of vacuolated clear cells. Some useful biomarkers can be Ki-67, P53, CK, PAS, S-100, EMA, and AR.

Chirurgie subkutaner Mastzelltumoren beim Hund: Prognosefaktoren und Outcome

2021 ◽  
Vol 49 (03) ◽  
pp. 228-228
Author(s):  
Daniela Simon Betz
Keyword(s):  
Mast Cell ◽  
Clinical Outcome ◽  
Proliferating Cell Nuclear Antigen ◽  
Prognostische Faktoren ◽  
Microvascular Density ◽  
Nuclear Antigen ◽  
Prognostic Indicators ◽  
Ki 67 ◽  
Mast Cell Tumors ◽  
Proliferating Cell

Gill V, Leibman N, Monette S et al. Prognostic Indicators and Clinical Outcome in Dogs with Subcutaneous Mast Cell Tumors. J Am Anim Hosp Assoc 2020; 56 (4): 215–225 Mastzelltumoren (MZT) sind häufige kutane Neoplasien beim Hund, für die verschiedene prognostische Faktoren beschrieben wurden. Zu diesen zählen der histologische Grad nach Patnaik (3 Grade) oder Kiupel (2 Grade) sowie einige Marker zellulärer Differenzierung wie AgNORs (agyrophylic nuclear organizer regions), Ki-67 oder PCNA (proliferating cell nuclear antigen). Weitere prognostisch aussagekräftige Parameter sind der c-Kit-Mutationsstatus, die mikrovaskuläre Dichte (microvascular density, MVD) und der mitotische Index (MI). Ziel der Studie war, den klinischen Verlauf nach operativer Entfernung subkutaner MZT beim Hund auszuwerten und die Wertigkeit der verschiedenen Prognosefaktoren zu validieren.

scholarly journals Kit Receptor Expression in Canine Cutaneous Mast Cell Tumors (CMCTs) Without C-Kit Mutation

2016 ◽  
Vol 66 (2) ◽  
pp. 222-233
Author(s):  
Ivana Vučićević ◽  
Darko Marinković ◽  
Vladimir Kukolj ◽  
Miloš Vučićević ◽  
Milorad Mirilović ◽  
...  
Keyword(s):  
Mast Cell ◽  
Histopathological Examination ◽  
Polymerase Chain Reaction Amplification ◽  
Histological Grade ◽  
Receptor Expression ◽  
Tissue Samples ◽  
Kit Mutation ◽  
Mast Cell Tumors ◽  
Kit Receptor ◽  
Cutaneous Mast Cell

Abstract Histopathological examination, grading, immunohistochemical staining and molecular genetic examinations are the proposed criteria that should be used for cutaneous mast cell tumors (CMCTs) classification. The presence of aberrant CD117 expression and mutations of the c-kit proto-oncogene could be an indicative parameter for final histological grading. Determination of the connection between the localization of KIT receptor expression and the histological grade of CMCTs without c-kit proto-oncogene mutations was the main goal of this study. The study included twenty four CMCTs and six control skin samples from 30 dogs of different ages, breed and sex. Formalinfixed and paraffin-embedded tissue samples were stained with hematoxylin-eosin and toluidine blue and immunohistochemically tested for CD117 expression. DNA was extracted from the same paraffin blocks and subsequent polymerase chain reaction amplification was performed using PE1 and PE2 primers. Degree of malignancy was determined based on the presence of mitotic figures, multinucleated cells, bizarre nuclei and karyomegaly in 10 high power fields. Based on histological features, fourteen of 24 CMCTs were of a high histological grade, while ten were classified as a lowgrade malignancy. CD117 cytoplasmic expression was observed in nine of fourteen high-grade malignancy CMCTs, which confirms the link between the aberrant CD117 expression and increased cell proliferation.

scholarly journals Disseminated Cutaneous Mast Cell Tumors with Epitheliotropism and Systemic Mastocytosis in a Domestic Cat

2009 ◽  
Vol 21 (5) ◽  
pp. 710-715 ◽  
Author(s):  
Catherine G. Lamm ◽  
Adam W. Stern ◽  
Amanda J. Smith ◽  
Emily J. Cooper ◽  
Steven W. Ullom ◽  
...  
Keyword(s):  
Mast Cell ◽  
Messenger Rna ◽  
Systemic Mastocytosis ◽  
Present Report ◽  
Skin Lesions ◽  
Domestic Cat ◽  
Neoplastic Cells ◽  
Diagnostic Laboratory ◽  
Mast Cell Tumors ◽  
Cutaneous Mast Cell

A 15-year-old female Domestic Medium Hair cat presented to the referring veterinarian with a 2-month history of multiple, raised, disseminated, nodular skin lesions. A biopsy of 1 of the lesions was submitted to the Oklahoma Animal Disease Diagnostic Laboratory for evaluation. Histologically, there were multiple dermal nodules composed of sheets of neoplastic round cells. Multifocally, the neoplastic cells formed multiple small clusters of 3–5 cells within the epidermis. Distinct cytoplasmic granules were evident within the neoplastic cells with toluidine blue and Giemsa stains. The neoplastic cells were immunoreactive for c-KIT and lacked immunoreactivity for cluster of differentiation 3 with immunohistochemistry. Based on these findings, multiple epitheliotropic cutaneous mast cell tumors were diagnosed. The cat's health declined rapidly despite aggressive treatment, and the animal was humanely euthanatized. A complete necropsy revealed sheets of similar neoplastic mast cells within the spleen, liver, and individual cells scattered within the bone marrow. Exon 11 of the c-KIT messenger RNA from 1 of the cutaneous masses and the spleen was amplified with reverse transcription polymerase chain reaction, sequenced, and compared with the published c-KIT messenger RNA sequence from fetal cat tissues. The maximum identity was 100% for both tissue samples. To the authors’ knowledge, the present report is the first to describe disseminated cutaneous mast cell tumors with epitheliotropism and systemic mastocytosis in a domestic cat.

Immunohistochemical and Histochemical Stains for Differentiating Canine Cutaneous Round Cell Tumors

2005 ◽  
Vol 42 (4) ◽  
pp. 437-445 ◽  
Author(s):  
N. J. Fernandez ◽  
K. H. West ◽  
M. L. Jackson ◽  
B. A. Kidney
Keyword(s):  
Mast Cell ◽  
Monoclonal Antibodies ◽  
Mast Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Positive Staining ◽  
Round Cell ◽  
Histologic Diagnosis ◽  
Mast Cell Tumors ◽  
Round Cell Tumors

Immunohistochemical and histochemical stains are useful adjunct techniques in the diagnosis of canine cutaneous round cell tumors, which can appear histologically similar We applied a panel of monoclonal antibodies (recognizing tryptase, chymase, serotonin for mast cells; CD1a, CD18, MHC class II for histiocytes; CD3 for T lymphocytes; CD79a for B lymphocytes and plasma cells) and one histochemical stain (naphthol AS-D chloroacetate for chymase activity) to formalin-fixed, paraffin-embedded sections of canine cutaneous mast cell tumors, histiocytomas, lymphosarcomas, plasmacytomas, and unidentified round cell tumors. Of 21 tumors with a histologic diagnosis of mast cell tumor, 7/7 (100%) grade I, 6/7 (85.7%) grade II, and 3/7 (42.9%) grade III tumors were diagnosed as mast cell tumors based on positive staining for tryptase antigen and chymase activity. Mast cells were positive for both tryptase antigen and chymase activity, indicating equal efficacy of tryptase immunohistochemistry and chymase histochemistry. Chymase was detected immunohistochemically in both tumor and nontumor cells, while serotonin was not detected in most mast cell tumors, and thus, neither was useful in the diagnosis of mast cell tumors. Immunohistochemistry to detect CD18 and MHC class II was equally effective in staining histiocytomas, although lymphosarcoma must be ruled out through the use of CD3 and CD79a immunohistochemistry. Immunohistochemistry using three different monoclonal antibodies to human CD1a showed no cross-reactivity in canine histiocytomas and was not useful. A final diagnosis was obtained for 4/5 (80%) of the unidentified tumors, indicating the usefulness of multiple stains in poorly differentiated round cell tumors.

Investigating Associations Between Proliferation Indices, C-kit, and Lymph Node Stage in Canine Mast Cell Tumors

2017 ◽  
Vol 53 (5) ◽  
pp. 258-264 ◽  
Author(s):  
Erika Lauren Krick ◽  
Matti Kiupel ◽  
Amy C. Durham ◽  
Tuddow Thaiwong ◽  
Dorothy C. Brown ◽  
...  
Keyword(s):  
Mast Cell ◽  
Lymph Node ◽  
Odds Ratio ◽  
Tandem Duplication ◽  
Stage Ii ◽  
Ki 67 ◽  
Internal Tandem Duplication ◽  
Mast Cell Tumors ◽  
Proliferation Indices ◽  
Grade Ii

ABSTRACT Previous studies have evaluated cellular proliferation indices, KIT expression, and c-kit mutations to predict the clinical behavior of canine mast cell tumors (MCTs). The study purpose was to retrospectively compare mitotic index, argyrophilic nucleolar organizer regions (AgNORs)/nucleus, Ki-67 index, KIT labeling pattern, and internal tandem duplication mutations in c-KIT between stage I and stage II grade II MCTs. Medical records and tumor biopsy samples from dogs with Grade II MCTs with cytological or histopathological regional lymph node evaluation were included. Signalment, tumor location and stage, and presence of a recurrent versus de novo tumor were recorded. Mitotic index, AgNORs/nucleus, Ki-67, KIT staining pattern, and internal tandem duplication mutations in exon 11 of c-KIT were evaluated. Sixty-six tumors (51 stage I; 15 stage II) were included. Only AgNORs/nucleus and recurrent tumors were significantly associated with stage (odds ratio 2.8, 95% confidence interval [CI] 1.0–8.0, P = .049; odds ratio 8.8, 95% CI 1.1–69.5; P = .039). Receiver-operator characteristic analysis showed that the sensitivity and specificity of AgNORs/cell ≥ 1.87 were 93.3% and 27.4%, respectively, (area under the curve: 0.65) for predicting stage. Recurrent tumors and higher AgNORs/nucleus are associated with stage II grade II MCTs; however, an AgNOR cutoff value that reliably predicts lymph node metastasis was not determined.

scholarly journals ATM Kinase Inhibition Preferentially Sensitises PTEN-Deficient Prostate Tumour Cells to Ionising Radiation

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 79
Author(s):  
Conor Hanna ◽  
Victoria L. Dunne ◽  
Steven M. Walker ◽  
Karl T. Butterworth ◽  
Nuala McCabe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cellular Response ◽  
Advanced Prostate Cancer ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Biochemical Failure ◽  
Ionising Radiation ◽  
Effective Treatment Option ◽  
Normal Prostate ◽  
Minimal Toxicity

Radical radiotherapy, often in combination with hormone ablation, is a safe and effective treatment option for localised or locally-advanced prostate cancer. However, up to 30% of patients with locally advanced PCa will go on to develop biochemical failure, within 5 years, following initial radiotherapy. Improving radiotherapy response is clinically important since patients exhibiting biochemical failure develop castrate-resistant metastatic disease for which there is no curative therapy and median survival is 8–18 months. The aim of this research was to determine if loss of PTEN (highly prevalent in advanced prostate cancer) is a novel therapeutic target in the treatment of advanced prostate cancer. Previous work has demonstrated PTEN-deficient cells are sensitised to inhibitors of ATM, a key regulator in the response to DSBs. Here, we have shown the role of PTEN in cellular response to IR was both complex and context-dependent. Secondly, we have confirmed ATM inhibition in PTEN-depleted cell models, enhances ionising radiation-induced cell killing with minimal toxicity to normal prostate RWPE-1 cells. Furthermore, combined treatment significantly inhibited PTEN-deficient tumour growth compared to PTEN-expressing counterparts, with minimal toxicity observed. We have further shown PTEN loss is accompanied by increased endogenous levels of ROS and DNA damage. Taken together, these findings provide pre-clinical data for future clinical evaluation of ATM inhibitors as a neoadjuvant/adjuvant in combination with radiation therapy in prostate cancer patients harbouring PTEN mutations.

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