Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes

Carbonic anhydrase IX (CA9) expression in multiple renal epithelial tumour subtypes
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DOI:
10.1111/his.14204
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发表时间:
2020-09-12
期刊:
影响因子:
6.4
通讯作者:
Hirsch, Michelle S.
Hirsch, Michelle S.
中科院分区:
医学2区
文献类型:
--
作者:
Baniak, Nicholas;Flood, Trevor A.;Hirsch, Michelle S.

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目的肾上皮肿瘤(RENs)可能很难细分,由于重叠的形态特征。碳酸酐酶9(CA 9)是透明细胞肾细胞癌(CCRCC)的常见生物标志物;然而,REN亚型的敏感性和特异性尚不清楚。本研究的目的是研究CA 9在RENs中的表达,特别是在与CCRCC和不常见实体的鉴别诊断中,以确定其作为诊断生物标志物的可靠性。方法与结果对262例RENs进行CA 9免疫组化染色,其中包括119例CCRCC和143例非CCRCC。免疫染色评价为阴性(0%)、罕见(1+,1-10%)、局灶性(2+,11-50%)或弥漫性(3+,>50%)。93%的CCRCC为3+ CA 9阳性; 4%为CA 9阴性。67%的乳头状肾细胞癌(RCC)为1+/2+ CA 9阳性,而33%为CA 9阴性。嫌色细胞RCC几乎总是CA 9阴性(93%),7%显示罕见的细胞反应性。透明细胞小管乳头状RCC(CCTPRCC)始终为3+ CA 9阳性,但具有杯状染色模式。53%的Xp11.2 RCC为CA 9阴性;然而,6%为3+ CA 9阳性,12%为2+ CA 9阳性。8例富马酸水合酶缺陷型RCC中有2例为3+ CA 9阳性。其余RCC的一小部分显示罕见至局灶性CA 9表达。所有嗜酸细胞瘤和嗜酸性实体和囊性RCC均为CA 9阴性。结论:总体而言,弥漫性CA 9表达在几乎所有的CCRCC和所有的CCTPRCC(高敏感性),但CA 9是不完全特异性。至少局灶性CA 9表达可以在许多RCC的一个子集中看到,这些发现应该与其他形态学,免疫表型和临床发现一起考虑。
Aims Renal epithelial neoplasms (RENs) can be difficult to subclassify, owing to overlapping morphological features. Carbonic anhydrase 9 (CA9) is a common biomarker for clear cell renal cell carcinoma (CCRCC); however, the sensitivity and specificity across REN subtypes are less clear. The aim of this study was to investigate CA9 expression in RENs, especially those in the differential diagnosis with CCRCC and less common entities, to determine its reliability as a diagnostic biomarker. Methods and results CA9 immunostaining was performed on 262 RENs, including 119 CCRCCs and 143 non-CCRCC. Immunostaining was evaluated as negative (0%), rare (1+, 1-10%), focal (2+, 11-50%), or diffuse (3+, >50%). CCRCCs were 3+ CA9-positive in 93% of cases; 4% were CA9-negative. Sixty-seven percent of papillary renal cell carcinomas (RCCs) were 1+/2+ CA9-positive, whereas 33% were CA9-negative. Chromophobe RCCs were nearly always CA9-negative (93%), with 7% showing rare cell reactivity. Clear cell tubulopapillary RCCs (CCTPRCCs) were consistently 3+ CA9-positive, but with a cup-like staining pattern. Fifty-three percent of Xp11.2 RCCs were CA9-negative; however, 6% were 3+ CA9-positive and 12% were 2+ CA9-positive. Two of eight fumarate hydratase-deficient RCCs were 3+ CA9-positive. A small subset of the remaining RCCs showed rare to focal CA9 expression. All oncocytomas and eosinophilic solid and cystic RCCs were CA9-negative. Conclusions Overall, diffuse CA9 expression was identified in nearly all CCRCCs and in all CCTPRCCs (high sensitivity); however, CA9 was not entirely specific. At least focal CA9 expression can been seen in a subset of many RCCs, and such findings should be taken into consideration with other morphological, immunophenotypic and clinical findings.