Bibbo Marluce, DeCecco Jennifer, Kovatich Albert J
Division of Cytopathology and Immunopathology, Department of Pathology, Thomas Jefferson University, 132 South 10th Street, Room 260, Main Building, Philadelphia, Pennsylania 19107, USA.
Anal Quant Cytol Histol. 2003 Feb;25(1):8-11.
To assess the utility of P16INK4A as an adjunct test in liquid-based cytology in cases with equivocal morphologic changes of high grade squamous intraepithelial lesion (HSIL).
P16INK4A immunoreactivity was investigated in residual ThinPrep material (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) from 30 cases with equivocal diagnoses of HSIL that had corresponding follow-up biopsies. Two control ThinPrep cases were included: 1 HSIL with biopsy-confirmed cervical intraepithelial neoplasia (CIN) 3 and a negative specimen with a corresponding biopsy of squamous metaplasia. The expression of P16INK4A in ThinPrep specimens and corresponding biopsies was scored as previously described. A ThinPrep case was scored positive if it contained > 10 abnormal cells with nuclear and cytoplasmic immunocytochemical staining. Corresponding biopsies were scored as having negative, sporadic, focal or diffuse staining.
The P16INK4A antibody assay was positive in 19 of 30 ThinPrep cases (63.3%). Seventeen of the 19 (89.4%) biopsies corresponding to the positively stained ThinPreps also were positive, with a score of at least focal positivity in the dysplastic regions (2 CIN 1, 4 CIN 2, 11 CIN 3; 2 lesions lost in the tissue recut). The assay was negative in 11 ThinPreps (36.6%) and 10 biopsies (33.3%) with tissue confirmation of chronic cervicitis (5), squamous metaplasia (2), CIN 1 (3) and 1 lesion lost in the tissue recut. Seventeen of 18 (94.4%) ThinPreps confirmed as high grade lesions upon biopsy showed P16INK4A positivity. The control HSIL case with a CIN 3 biopsy was diffusely positive for P16INK4A, and the control negative case with biopsy diagnosis of squamous metaplasia was negative. Nondysplastic squamous and metaplastic epithelium in 7 biopsies and nondysplastic squamous or metaplastic cells in ThinPrep cases were negative. Sporadic staining of bacteria, inflammatory cells and endocervical cells was noted.
ThinPrep cases in the equivocal cytologic category with the corresponding tissue biopsy assayed for P16INK4A expression showed that there was utility for this type of testing. A larger series comparing corresponding ThinPrep and tissue biopsies will be undertaken. The role of HPV infection in these cases will also be explored.
评估P16INK4A作为高级别鳞状上皮内病变（HSIL）形态学改变不明确病例的液基细胞学辅助检测的效用。
对30例HSIL诊断不明确且有相应随访活检的病例的剩余ThinPrep样本（美国马萨诸塞州博克斯伯勒的Cytyc公司）进行P16INK4A免疫反应性研究。纳入2例对照ThinPrep病例：1例活检确诊为宫颈上皮内瘤变（CIN）3级的HSIL病例和1例鳞状化生相应活检为阴性的样本。按照先前描述对ThinPrep样本和相应活检中P16INK4A的表达进行评分。如果ThinPrep病例含有>10个具有核和细胞质免疫细胞化学染色的异常细胞，则评为阳性。相应活检根据染色情况评为阴性、散在、局灶或弥漫性染色。
30例ThinPrep病例中有19例（63.3%）P16INK4A抗体检测呈阳性。19例ThinPrep样本染色阳性对应的活检中有17例（89.4%）也呈阳性，发育异常区域的评分为至少局灶性阳性（2例CIN 1级、4例CIN 2级、11例CIN 3级；2例病变在组织重切中丢失）。11例ThinPrep样本（36.6%）和10例活检（33.3%）检测为阴性，组织学证实为慢性宫颈炎（5例）、鳞状化生（2例）、CIN 1级（3例），1例病变在组织重切中丢失。18例活检确诊为高级别病变的ThinPrep样本中有17例（94.4%）显示P16INK4A阳性。活检为CIN 3级的对照HSIL病例P16INK4A弥漫性阳性，活检诊断为鳞状化生的对照阴性病例为阴性。7例活检中的非发育异常鳞状上皮和化生上皮以及ThinPrep病例中的非发育异常鳞状或化生细胞均为阴性。观察到细菌、炎性细胞和宫颈管细胞的散在染色。
对形态学改变不明确的ThinPrep病例及相应组织活检进行P16INK4A表达检测表明这种检测是有用的。将开展更大规模的系列研究比较相应的ThinPrep样本和组织活检。还将探讨HPV感染在这些病例中的作用。
