Sabattini Silvia, Giantin Mery, Barbanera Adele, Zorro Shahidian Lara, Dacasto Mauro, Zancanella Vanessa, Prata Daniela, Trivigno Eleonora, Bettini Giuliano
Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.
Department of Comparative Biomedicine and Food Science, University of Padua, Padua, Italy.
J Feline Med Surg. 2016 Apr;18(4):280-9. doi: 10.1177/1098612X15581205. Epub 2015 Apr 27.
Feline intestinal mast cell tumours (FIMCTs) are rare and reportedly characterised by poor differentiation, aggressive biological behaviour and lack of reliable therapeutic aids. KIT proto-oncogene-activating mutations have never been investigated in these tumours. This study describes the main clinicopathological and microscopic features observed in 17 FIMCTs.
Tumour degree of differentiation, proliferative activity, Kit protein expression and KIT mutations were evaluated and correlated with survival to assess their prognostic relevance.
Ten tumours were located in the small intestine, two in the ileocaecocolic junction, and five in the large intestine. Survival times ranged from 3-538 days. Fifteen tumours were evaluated histologically, and there were six well-differentiated, six moderately differentiated and three poorly differentiated FIMCTs. The last showed a medium-to-large deposition of collagen tissue (P <0.001), and significantly higher mitotic and Ki67 indexes compared with more differentiated tumours (P = 0.011). On survival analysis, tumour degree of differentiation (P <0.001) and a mitotic index >2 (P = 0.022) were significantly associated with decreased survival times. Twelve cases showed Kit protein immunoexpression. The Kit pattern was membranous in five cases (33.3%), focal paranuclear in five (33.3%) and diffuse cytoplasmic in two (13.3%). Cytoplasmic Kit patterns were associated with a lesser differentiation (P = 0.015). Mutation analysis was successfully performed on 12 primary tumours and four lymph node metastases; however, no encoding mutation was detected.
Contrary to reports in the literature, FIMCTs seem to have an extremely variable biological behaviour. We propose a classification based on tumour degree of differentiation and proliferative activity. These findings need to be confirmed in larger series, and exploration of further genomic regions of KIT is warranted to clarify its role in the development and progression of these neoplasms.
猫肠道肥大细胞瘤(FIMCTs)较为罕见,据报道其特征为分化差、生物学行为侵袭性强且缺乏可靠的治疗辅助手段。KIT原癌基因激活突变在这些肿瘤中从未被研究过。本研究描述了17例FIMCTs的主要临床病理和微观特征。
评估肿瘤的分化程度、增殖活性、Kit蛋白表达和KIT突变,并与生存情况相关联以评估其预后相关性。
10例肿瘤位于小肠,2例位于回盲结肠交界处,5例位于大肠。生存时间为3 - 538天。对15例肿瘤进行了组织学评估,其中有6例高分化、6例中分化和3例低分化FIMCTs。低分化肿瘤显示出中到大程度的胶原组织沉积(P <0.001),与分化程度更高的肿瘤相比,有丝分裂和Ki67指数显著更高(P = 0.011)。生存分析显示,肿瘤分化程度(P <0.001)和有丝分裂指数>2(P = 0.022)与生存时间缩短显著相关。12例病例显示Kit蛋白免疫表达。Kit模式在5例(33.3%)中为膜性,5例(33.3%)为局灶性核旁,2例(13.3%)为弥漫性细胞质。细胞质Kit模式与较低的分化程度相关(P = 0.015)。对12例原发性肿瘤和4例淋巴结转移灶成功进行了突变分析;然而,未检测到编码突变。
与文献报道相反,FIMCTs似乎具有极其多变的生物学行为。我们提出了一种基于肿瘤分化程度和增殖活性的分类方法。这些发现需要在更大的系列研究中得到证实,并且有必要进一步探索KIT的基因组区域以阐明其在这些肿瘤发生和发展中的作用。