TSLC1 tumour-suppressor gene expression in canine mast cell tumours

Abstract

Tumour suppressor in lung cancer-1 (TSLC1) is a tumour-suppressor gene coding for an adhesion molecule that is expressed by mast cells. Reduced TSLC1 expression is associated with a poor prognosis in several human tumours, and this study sought to investigate if TSLC1 expression could be used to predict outcome in dogs with mast cell tumours (MCTs). Sections of MCTs of different tumour grades from 45 dogs (Group 1) were immunohistochemically assessed for TSLC1 and Ki67 expression. In addition, 35 intermediate-grade MCTs (Group 2) from dogs with known clinical follow-up were immunohistochemically stained for TSLC1 and Ki67. The TSLC1 staining intensity was found to strongly inversely correlate with tumour grade for Group 1 (P = 0.002857). For Group 2 there was a trend towards dogs with lower TSLC1 scores being more likely to die from MCT-related disease (P = 0.058). The intensity of TSLC1 staining inversely correlated with Ki67 expression for both groups.

Breed-Predispositions to Cancer in Pedigree Dogs

“…Tumour suppressor in lung cancer-1 ( TSLC1 ) is a tumour-suppressor gene coding for an adhesion molecule that is involved in normal mast cell to mast cell, and mast cell to fibroblast interactions [147] Loss of TSLC1 expression is associated with a poor prognosis in various human tumours, including non-small cell lung cancer, breast, prostate, oesophageal and gastric tumours [148–150] and has been shown to correlate with grade in canine MCTs [151]. In humans, mutations in the mismatch repair (MMR) genes give rise to Lynch syndrome, an inherited predisposition to early onset cancer, especially intestinal adenocarcinoma and skin cancer [152].…”

Use of neutrophil to lymphocyte ratio for predicting histopathological grade of canine mast cell tumours

“…A two-tiered (Kiupel and others 2011) and a three-tiered grading system (Patnaik and others 1984) are both currently used. Numerous histopathological proliferation indices and markers have also been utilised in attempt to better determine the biological behaviour of a MCT: argyrophilic nucleolar-organising regions (Bostock and others 1989, Scase and others 2006, Webster and others 2007, 2008), B-cell lymphoma 2 (BCL-2) gene and protein expression (Vascellari and others 2013), Ki-67 (Abadie and others 1999, Scase and others 2006, Ozaki and others 2007, Webster and others 2007, 2008, Maglennon and others 2008), KIT staining pattern, presence of mutations in KIT or alterations in other receptor tyrosine kinases (Zemke and others 2002, Kiupel and others 2004, Webster and others 2007, 2008, Thompson and others 2015), minichromosome maintenance protein 7 (Berlato and others 2012), mitotic index (Bostock and others 1989, Sakai and others 2002, Elston and others 2007, Romansik and others 2007, Vascellari and others 2013, Van Lelyveld and others 2015), tumour suppressor in lung cancer 1 (Taylor and others 2010) and combinations of multiple markers or indices (Simoes and others 1994, Séguin and others 2006). …”

<b>Valor prognóstico de marcadores imunohistoquímicos em mastocitomas cutâneos caninos</b>

“…PALTRINIERI, 2004), as proteínas relacionadas a apoptose, como BAX, Bcl-2 e survivina (SCASE et al, 2006;STREFEZZI et al, 2012;VASCELLARI et al, 2013) e proteínas relacionadas a inflamação, como prostaglandina E2 e o inibidor de ciclooxigenase 2, COX-2 (AMORIM et al, 2010;PRADA et al, 2012) Os cinco estudos reunidos compreenderam um total de 329 animais e 331 tumores (ABADIE; AMARDEILH; DELVERDIER, 1999;WEBSTER et al, 2008;TAYLOR et al, 2010;VASCELLARI et al, 2013;BERLATO et al, 2015). Em apenas em um dos estudos, a correlação com a sobrevida não foi significante (TAYLOR et al, 2010). Este estudo também foi o único que avaliou uma coorte constituída apenas por MCTs grau II (Patnaik et al, 1984) (WEBSTER et al, 2006) e graduação histológica (GIL DA COSTA et al, 2007;REBUZZI et al, 2007;PATRUNO et al, 2009;KANDEFER-GOLA et al, 2015).…”

“…(5/46) de todos os estudos inteiramente revisados apresentavam o valor de Hazard ratio descrito no artigo (KIUPEL et al, 2004;SCASE et al, 2006;WEBSTER et al, 2007;MAGLENNON et al, 2008;BERLATO et al, 2015). Adicionalmente, 13% (6/46) dos trabalhos foram excluídos por serem os únicos trabalhos que avaliaram um determinado alvo como marcador imunohistoquímico (PREZIOSI; SARLI; PALTRINIERI, 2004;BERLATO et al, 2012;MACKOWIAK et al, 2012;STREFEZZI et al, 2012;VARGAS et al, 2015 GINN et al, 2000;JAFFE et al, 2000;KIUPEL et al, 2004;MORINI;SCASE et al, 2006;OZAKI et al, 2007;WEBSTER et al, 2008;TAYLOR et al, 2010;GIANTIN et al, 2012a;BERLATO et al, 2015;COSTA CASAGRANDE et al, 2015;VAN LELYVELD et al, 2015). Porém, apenas 18,7%…”

“…(3/16) destes estudos apresentaram o Hazard ratio e os intervalos de confiança (SCASE et al, 2006;MAGLENNON et al, 2008;BERLATO et al, 2015 WEBSTER et al, 2008;TAYLOR et al, 2010;VASCELLARI et al, 2013;BERLATO et al, 2015) e 28,6% (2/7) avaliaram o receptor de tirosina quinase KIT (KIUPEL et al, 2004;COSTA CASAGRANDE et al, 2015). Outros dois trabalhos que avaliaram o marcador de proliferação celular Ki67 forneceram os valores de Hazard ratio (SCASE et al, 2006;MAGLENNON et al, 2008) KIT (KIUPEL et al, 2004;COSTA CASAGRANDE et al, 2015) foram avaliados segundo os padrões propostos por Kiupel et al (2004), sendo eles: KIT 1 -marcação associada à membrana com pouca ou nenhuma coloração citoplasmática;…”