Lilo Mohammed T, Allison Derek, Wang Yuting, Ao MingHui, Gabrielson Edward, Geddes Susan, Zhang Hui, Askin Frederic, Li Qing Kay
The Department of Pathology, the Johns Hopkins Medical Institutions, Baltimore, MD 21224.
The Department of Chemistry, Magdalen College, University of Oxford, OX1 4AU, United Kingdom.
J Am Soc Cytopathol. 2016 May-Jun;5(3):123-132. doi: 10.1016/j.jasc.2015.07.002.
Fine-needle aspiration (FNA) biopsy of lung lesions is a highly accurate method for diagnosing and staging of lung cancers, particularly in patients with advanced cancer. Although, the majority of FNA cases of non-small cell lung carcinoma (NSCLC) can be subclassified by hematoxylin and eosin (H&E) sections, immunohistochemical (IHC) markers are usually necessary for difficult cases. Our previous study has shown that both P40 and P63 demonstrate differential sensitivity and specificity in the subclassification of squamous cell carcinoma (SqCC) using tumor tissue microarrays (TMA). In the present study, we further evaluated the utility of P40 and P63 and the potential pitfalls and limitations associated with the usefulness of these stains in FNA cases.
By a computer search of pathology archives, 144 FNA biopsies with diagnoses of lung cancers and P40/P63 stains were identified, including 50 adenocarcinomas (ADCs), 56 SqCCs, 8 small cell lung carcinomas (SCLCs), and 12 cases of poorly differentiated carcinoma (PD CA). Ten benign FNA lung lesions and 8 other malignant neoplasms were also included as controls. Nuclear staining patterns of P40 and P63 were scored semi-quantitatively as 0 (negative), 1 (<10%, weak and focal), or 2 (>10%, strong and diffuse).
In lung SqCCs, P40 and P63 were positive in 77.3% and 89.5% cases, respectively. In ADCs, P40 was weakly and focally positive in 6.1% cases, and P63 was variably positive in 62.8% cases. In SCLCs, P40 and P63 were focally positive in 12.5% and 50% cases. In PD CAs, no P40 or P63 immunoreactivity was detected. In the group of other neoplasms (n=8) both P40 and P63 were positive in the case of metastatic non-seminomatous germ cell tumor (NSGCT) (n=1), and P63 was positive in the case of metastatic Merkel cell carcinoma (n=1). The sensitivity and specificity of P40 and P63 were 76.9%/93.3%, and 90.2%/50.7% in the lung SqCC.
P63 has a better sensitivity, and P40 has a better specificity for SqCC. A positive staining pattern with both markers was also found in certain non-SqCC cases. Recognizing limitations of these markers are particularly important in FNA cases.
肺病变的细针穿刺（FNA）活检是诊断肺癌及进行分期的一种高度准确的方法，尤其对于晚期癌症患者。虽然，大多数非小细胞肺癌（NSCLC）的FNA病例可通过苏木精和伊红（H&E）切片进行亚分类，但对于疑难病例，免疫组化（IHC）标志物通常是必需的。我们之前的研究表明，P40和P63在使用肿瘤组织微阵列（TMA）对鳞状细胞癌（SqCC）进行亚分类时表现出不同的敏感性和特异性。在本研究中，我们进一步评估了P40和P63的效用以及与这些染色在FNA病例中的实用性相关的潜在陷阱和局限性。
通过计算机检索病理档案，确定了144例诊断为肺癌且有P40/P63染色的FNA活检病例，包括50例腺癌（ADC）、56例SqCC、8例小细胞肺癌（SCLC）和12例低分化癌（PD CA）。还纳入了10例良性FNA肺病变和8例其他恶性肿瘤作为对照。P40和P63的核染色模式进行半定量评分，分别为0（阴性）、1（<10%，弱阳性且局灶性）或2（>10%，强阳性且弥漫性）。
在肺SqCC中，P40和P63分别在77.3%和89.5%的病例中呈阳性。在ADC中，P40在6.1%的病例中呈弱阳性且局灶性阳性，P63在62.8%的病例中呈不同程度阳性。在SCLC中，P40和P63分别在12.5%和50%的病例中呈局灶性阳性。在PD CA中，未检测到P40或P63免疫反应性。在其他肿瘤组（n = 8）中，转移性非精原细胞瘤（NSGCT）（n = 1）病例中P40和P63均呈阳性，转移性默克尔细胞癌（n = 1）病例中P63呈阳性。在肺SqCC中，P40和P63的敏感性和特异性分别为76.9%/93.3%和90.2%/50.7%。
对于SqCC，P63具有更好的敏感性，P40具有更好的特异性。在某些非SqCC病例中也发现了两种标志物均呈阳性的染色模式。在FNA病例中认识到这些标志物的局限性尤为重要。
