Džombeta Tihana, Krušlin Božo
Department of Pathology, School of Medicine, University of Zagreb, Šalata 10, 10 000, Zagreb, Croatia.
Department of Pathology, Clinical Hospital Centre Sestre milosrdnice, Vinogradska 29, 10 000, Zagreb, Croatia.
Pathol Oncol Res. 2018 Jul;24(3):567-574. doi: 10.1007/s12253-017-0279-2. Epub 2017 Jul 27.
Differentiation of noninvasive from invasive papillary urothelial carcinoma can be challenging due to inability of proper orientation and thermal damage of transurethrally obtained material. The aim of this study was to analyze the presence and extent of peritumoral retractions in pT1 compared to pTa papillary urothelial carcinoma. Since peritumoral retractions may result from altered expression profiles of extracellular matrix proteins, we additionally analyzed the expression of matrix metalloproteinase 2 (MMP-2) and interleukin 8 (IL-8) in these tumors. The study comprised 50 noninvasive (pTa) and 50 invasive (pT1) cases of transurethrally obtained primary papillary urothelial carcinomas. The invasive nature of nests showing peritumoral retractions was confirmed immunohistochemically using antibody against collagen IV. Staining for MMP-2 and IL-8 was evaluated semiquantitatively using immunohistochemical staining index, calculated by multiplying the percentage of positive cells and staining intensity. Peritumoral retractions were found in 32% of pT1 carcinomas but in none of the pTa carcinomas. All tumors showing peritumoral retraction were high grade tumors. There was no statistically significant correlation between the expression of MMP-2 or IL-8 and the presence of peritumoral retractions or stage of the tumor (pTa vs. pT1). A statistically significant but weak correlation was found between MMP-2 and IL-8 expression (χ2-test, p=0,015). There was no statistically significant correlation between the presence of peritumoral retractions or MMP-2 expression and tumor recurrence and progression. Our study shows that, in doubtful cases, when differentiating between pTa and pT1 stages of papillary urothelial carcinoma, the presence of peritumoral retractions could favor the diagnosis of invasive neoplasm.
由于经尿道获取的材料无法正确定位以及热损伤,区分非侵袭性与侵袭性乳头状尿路上皮癌具有挑战性。本研究的目的是分析与pTa乳头状尿路上皮癌相比,pT1肿瘤周围退缩的存在情况及范围。由于肿瘤周围退缩可能是细胞外基质蛋白表达谱改变所致,我们还分析了这些肿瘤中基质金属蛋白酶2(MMP-2)和白细胞介素8(IL-8)的表达。该研究包括50例经尿道获取的原发性非侵袭性(pTa)和50例侵袭性(pT1)乳头状尿路上皮癌病例。使用抗IV型胶原抗体通过免疫组织化学证实显示肿瘤周围退缩的巢状结构的侵袭性质。使用免疫组织化学染色指数对MMP-2和IL-8染色进行半定量评估,该指数通过将阳性细胞百分比与染色强度相乘计算得出。在32%的pT1癌中发现肿瘤周围退缩,但在pTa癌中均未发现。所有显示肿瘤周围退缩的肿瘤均为高级别肿瘤。MMP-2或IL-8的表达与肿瘤周围退缩的存在或肿瘤分期(pTa与pT1)之间无统计学显著相关性。在MMP-2和IL-8表达之间发现有统计学显著但较弱的相关性(χ2检验,p = 0.015)。肿瘤周围退缩的存在或MMP-2表达与肿瘤复发和进展之间无统计学显著相关性。我们的研究表明,在可疑病例中,当区分乳头状尿路上皮癌的pTa和pT1期时,肿瘤周围退缩的存在可能有助于侵袭性肿瘤的诊断。