ANXA10 Expression Is Inversely Associated with Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma
ANXA10 Expression Is Inversely Associated with Tumor Stage, Grade, and TP53 Expression in Upper and Lower Urothelial Carcinoma
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DOI：
10.1159/000524989
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发表时间：
2022-07
期刊：
影响因子：
5
通讯作者：
G. Kobayashi;Tetsutaro Hayashi;K. Sentani;K. Ikeda;T. Babasaki;Yoshinori Shigematsu;Yohei Sekino;N. Uraoka;J. Teishima;A. Matsubara;N. Hinata;N. Oue
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作者：
G. Kobayashi;Tetsutaro Hayashi;K. Sentani;K. Ikeda;T. Babasaki;Yoshinori Shigematsu;Yohei Sekino;N. Uraoka;J. Teishima;A. Matsubara;N. Hinata;N. Oue
简介：尿路上皮癌（UC）是一种常见的恶性肿瘤，但由于其发病率低，对上尿路尿路上皮癌（UTUC）的诊断和预后指标了解甚少。为了阐明ANXA 10在UTUC中的意义，我们用免疫组织化学（IHC）研究了ANXA 10的表达。研究方法：通过IHC结合癌症基因组图谱（TCGA）数据分析分析UC上尿路和下尿路中ANXA 10的表达。还评估了ANXA 10表达与代表性癌症相关分子之间的关联。结果：ANXA 10在正常上尿路上皮中表达较弱，在UTUC中阳性表达率为33%（39/117）。ANXA 10在单纯UC肿瘤中更常见（36%，p < 0.05），乳头状形态（50%，p < 0.01），低级别（G1/2：57%，p < 0.01）和pTa/is/1期（55%，p < 0.01），而分别为组织学变异（0%）、结节形态（9%）、G3（16%）和pT 2/3/4（13%）。ANXA 10阳性患者的癌症特异性生存期和无进展生存期优于ANXA 10阴性患者（p < 0.05）。免疫组化结果显示，在TP 53低表达（p < 0.01）和Ki-67标记指数<20%（p < 0.01）的病例中，ANXA 10阳性率较高。在肌层浸润性膀胱癌的TCGA数据集中，较高的ANXA 10表达与乳头状形态、较低级别/分期、管腔乳头状亚型、野生型TP 53和FGFR 3基因突变相关。结论：我们发现ANXA 10表达在癌变过程中增加，并且在较低级别和阶段的乳头状UC中更常见。然而，其表达随着癌症进展而降低。因此，UTUC中ANXA 10的表达可能对临床决策有用。
Introduction: Urothelial carcinoma (UC) is a common type of malignant disease, but little is known about the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) because of its rarity. To clarify the significance of ANXA10 in UTUC, we studied ANXA10 expression with immunohistochemistry (IHC). Methods: The expression of ANXA10 was analyzed in the upper and lower urinary tract of UC by IHC in combination with The Cancer Genome Atlas (TCGA) data analysis. The association between ANXA10 expression and representative cancer-related molecules was also evaluated. Results: ANXA10 expression was weak in normal upper tract urothelium but was positive in 39/117 (33%) UTUCs. ANXA10 was more frequently positive in tumors with pure UC (36%, p < 0.05), papillary morphology (50%, p < 0.01), low grade (G1/2: 57%, p < 0.01), and pTa/is/1 stage (55%, p < 0.01) than in those with histological variants (0%), nodular morphology (9%), G3 (16%), and pT2/3/4 (13%), respectively. ANXA10-positive patients showed better cancer-specific survival and progression-free survival than ANXA10-negative patients (p < 0.05). IHC showed that ANXA10 positivity was detected more in cases with the low expression of TP53 (p < 0.01) and Ki-67 labeling index <20% (p < 0.01). In TCGA dataset of muscle-invasive bladder cancer, higher ANXA10 expression correlated with papillary morphology, lower grade/stage, luminal papillary subtype, wild-type TP53, and FGFR3 gene mutation. Conclusion: We revealed that ANXA10 expression was increased during carcinogenesis and was observed more frequently in papillary UC of lower grade and stage. However, its expression decreased as cancer progressed. Therefore, the ANXA10 expression in UTUC might be clinically useful for decision-making.