Department of Pathology, Central Hospital Bolzano, Bolzano, Italy.
Int J Gynecol Pathol. 2011 Jul;30(4):407-13. doi: 10.1097/PGP.0b013e31820a79b0.
Although the diagnostic criteria of in-situ and invasive adenocarcinomas of the cervix uteri are well established, the differentiation from benign mimics may be difficult and the morphologic features of the precursors of endocervical adenocarcinoma are still debated. In this study, we evaluated the usefulness of p16ink4a (p16), ProEX C, and Ki-67 for the diagnosis of endocervical adenocarcinoma and its precursors. Immunohistochemistry with p16, ProEX C, and Ki-67 was performed in 82 glandular lesions including 15 invasive adenocarcinomas, 29 adenocarcinomas in situ (AIS), 22 non-neoplastic samples, and 16 cases of glandular dysplasia (GD), which showed significant nuclear abnormalities but did not meet the diagnostic criteria for AIS. The immunohistochemical expression pattern was scored according to the percentage of the stained cells (0, 1+, 2+, and 3+ when 0% to 5%, 6% to 25%, 26% to 50%, and more than 50% of the cells were stained, respectively) and was evaluated for each antibody. p16 was at least focally expressed (1+ or more) in 14 of 15 invasive adenocarcinomas, in all AIS and in 7 negative samples. ProEX C and Ki-67 both scored 1+ or more in all adenocarcinomas and AIS and in 8 and 6 negative samples, respectively. Of the GD 15, 14, and 15 expressed p16, ProEX C, and Ki-67, respectively. The score differences between neoplastic and non-neoplastic samples were highly significant for each marker (P<0.001); however, the score distribution by marker differed significantly only in GD (P=0.006) in which, compared with the other markers, p16 showed more often a 3+ pattern. Our study shows that p16, Ki-67, and ProEX C may be helpful for the diagnosis of glandular lesions of the cervix uteri and may also improve the diagnostic accuracy of endocervical GD. In particularly problematic cases, the combination of p16 and a proliferation marker can provide additional help for the interpretation of these lesions.
虽然子宫颈原位和浸润性腺癌的诊断标准已经确立，但良性模拟物的鉴别可能很困难，而且内宫颈腺癌前体的形态学特征仍存在争议。在这项研究中，我们评估了 p16ink4a(p16)、ProEX C 和 Ki-67 对诊断内宫颈腺癌及其前体的有用性。对 82 例腺性病变进行了 p16、ProEX C 和 Ki-67 的免疫组织化学染色，包括 15 例浸润性腺癌、29 例原位腺癌(AIS)、22 例非肿瘤性样本和 16 例腺性发育不良(GD)。这些样本显示出明显的核异常，但不符合 AIS 的诊断标准。根据染色细胞的百分比(分别为 0%至 5%、6%至 25%、26%至 50%和超过 50%的细胞染色时为 0、1+、2+和 3+)对免疫组化表达模式进行评分，并对每种抗体进行评估。p16 在 15 例浸润性腺癌中的 14 例、所有 AIS 中和 7 例阴性样本中至少局灶性表达(1+或更高)。ProEX C 和 Ki-67 在所有腺癌和 AIS 中均为 1+或更高，在 8 例和 6 例阴性样本中分别为 1+或更高。在 15 例 GD 中，分别有 14、14 和 15 例表达 p16、ProEX C 和 Ki-67。每个标志物的肿瘤和非肿瘤样本之间的评分差异均具有统计学意义(P<0.001)；然而，仅在 GD 中，标志物的评分分布存在显著差异(P=0.006)，与其他标志物相比，p16 更常出现 3+模式。我们的研究表明，p16、Ki-67 和 ProEX C 可能有助于诊断子宫颈腺性病变，也可能提高内宫颈 GD 的诊断准确性。在特别棘手的病例中，p16 与增殖标志物的联合应用可为这些病变的解释提供额外帮助。
