目的:疣状棘皮外阴上皮内瘤变(vaVIN)是一种不依赖HPV的,p53野生型病变具有独特的形态和记录的复发和癌症进展的风险。vavin是罕见的,与非肿瘤性增生性病变的前瞻性区分可能很困难。CK17、SOX2和GATA3免疫组织化学在HPV非依赖性病变的诊断中具有新的价值,特别差异化的VIN。我们旨在测试这些标志物在vaVIN诊断中的综合价值及其在外阴中的非肿瘤性差异。
结果:CK17,SOX2和GATA3免疫组织化学在16个vaVINs和34个模拟物上进行了评估(疣状黄瘤,慢性单纯性地衣,硬化性苔藓,牛皮癣,假性上皮瘤增生)。CK17评分为3+=全厚度,2+=局部厚度,1+=斑片状,0=不存在;SOX2为3+=强染色≥10%细胞,2+=中度,1+=弱,0=在<10%细胞中染色;GATA3为模式0=在<25%基底细胞中丢失,1=25-75%基底细胞损失,2=>75%基底细胞的损失。为了进行分析,结果记录为阳性(CK17=3+,SOX2=3+,GATA3=模式1/2)或阴性(CK17=2/1/0,SOX2=2/1/0,GATA3=模式0)。CK17,SOX2和GATA3阳性记录在81%,75%和58%的vaVIN中,分别,与32%,17%和22%的非肿瘤模仿者相比,分别;≥2个标记阳性赋予83个灵敏度,vaVIN诊断的特异性为88%,准确率为86%。与vaVIN相比,SOX2和GATA3在硬化性苔藓中差异表达,慢性单纯性苔藓和假性上皮瘤增生,而CK17在疣状黄色瘤和邻近的正常粘膜中差异表达。
结论:CK17,SOX2和GATA3可用于vaVIN的诊断及其与增生性非肿瘤性外阴病变的区别。虽然CK17具有更高的灵敏度,SOX2和GATA3更具体,所有标记物的组合显示出最佳的诊断准确性。
OBJECTIVE: Verruciform acanthotic vulvar intra-epithelial neoplasia (vaVIN) is an HPV-independent, p53 wild-type lesion with distinct morphology and documented risk of recurrence and cancer progression. vaVIN is rare, and prospective distinction from non-neoplastic hyperplastic lesions can be difficult. CK17, SOX2 and GATA3 immunohistochemistry has emerging value in the diagnosis of HPV-independent lesions, particularly differentiated VIN. We aimed to test the combined value of these markers in the diagnosis of vaVIN versus its non-neoplastic differentials in the vulva.
RESULTS: CK17, SOX2 and GATA3 immunohistochemistry was evaluated on 16 vaVINs and 34 mimickers (verruciform xanthoma, lichen simplex chronicus, lichen sclerosus, psoriasis, pseudo-epitheliomatous hyperplasia). CK17 was scored as 3+ = full-thickness, 2+ = partial-thickness, 1+ = patchy, 0 = absent; SOX2 as 3+ = strong staining ≥ 10% cells, 2+ = moderate, 1 + =weak, 0 = staining in < 10% cells; and GATA3 as pattern 0 = loss in < 25% basal cells, 1 = loss in 25-75% basal cells, 2 = loss in > 75% basal cells. For analysis, results were recorded as positive (CK17 = 3+, SOX2 = 3+, GATA3 = patterns 1/2) or negative (CK17 = 2+/1+/0, SOX2 = 2+/1+/0, GATA3 = pattern 0). CK17, SOX2 and GATA3 positivity was documented in 81, 75 and 58% vaVINs, respectively, versus 32, 17 and 22% of non-neoplastic mimickers, respectively; ≥ 2 marker positivity conferred 83 sensitivity, 88 specificity and 86% accuracy in vaVIN diagnosis. Compared to vaVIN, SOX2 and GATA3 were differentially expressed in lichen sclerosus, lichen simplex chronicus and pseudo-epitheliomatous hyperplasia, whereas CK17 was differentially expressed in verruciform xanthoma and adjacent normal mucosa.
CONCLUSIONS: CK17, SOX2 and GATA3 can be useful in the diagnosis of vaVIN and its distinction from hyperplastic non-neoplastic vulvar lesions. Although CK17 has higher sensitivity, SOX2 and GATA3 are more specific, and the combination of all markers shows optimal diagnostic accuracy.