Ronen Shira, Abbott Daniel W, Kravtsov Oleksandr, Abdelkader Amrou, Xu Yayun, Banerjee Anjishnu, Iczkowski Kenneth A
Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Hum Pathol. 2017 Jul;65:85-91. doi: 10.1016/j.humpath.2017.04.024. Epub 2017 May 10.
The presence and extent of cribriform pattern of prostate cancer portend recurrence and cancer death. The relative expressions within this morphology of the prognostically adverse loss of PTEN, and the downstream inactivation of cell cycle inhibitor p27/Kip1 had been uncertain. In this study, we examined 52 cases of cribriform cancer by immunohistochemistry for PTEN, p27, and CD44 variant (v)7/8, and a subset of 17 cases by chromogenic in situ hybridization (ISH) using probes for PTEN or CDKN1B (gene for p27). The fractions of epithelial pixels positive by immunohistochemistry and ISH were digitally assessed for benign acini, high-grade prostatic intraepithelial neoplasia, and 8 morphologic patterns of cancer. Immunostaining results demonstrated that (1) PTEN loss was significant for fused small acini, cribriform-central cells, small cribriform acini, and Gleason grade 5 cells in comparison with other acini; (2) p27 loss was significant only for cribriform-peripheral cells and borderline significant for fused small acini in comparison with benign acini; and (3) CD44v7/8 showed expression loss in cribriform-peripheral cells; other comparisons were not significant. ISH showed that cribriform cancer had significant PTEN loss normalized to benign acini (P<.02), whereas Gleason 3 cancer or fused small acini did not. With CDKN1B, the degree of signal loss among various cancer morphologies was insignificant. In conclusion, molecular disparities emerged between the fused small acini and cribriform patterns of Gleason 4 cancer. PTEN or p27 loss as prognostic factors demands distinct assessment in the varieties of Gleason 4 cancer, and in the biphenotypic peripheral versus central populations in cribriform structures.
前列腺癌筛状结构的存在及范围预示着复发和癌症死亡。在这种形态学中，预后不良的PTEN缺失以及细胞周期抑制剂p27/Kip1的下游失活的相对表达情况尚不确定。在本研究中，我们通过免疫组织化学检测了52例筛状癌的PTEN、p27和CD44变异体（v）7/8，并使用PTEN或CDKN1B（p27的基因）探针通过显色原位杂交（ISH）检测了17例的一个亚组。通过免疫组织化学和ISH检测为阳性的上皮像素分数，针对良性腺泡、高级别前列腺上皮内瘤变和8种癌症形态学模式进行了数字评估。免疫染色结果表明：（1）与其他腺泡相比，融合性小腺泡、筛状中央细胞、小筛状腺泡和Gleason 5级细胞中的PTEN缺失显著；（2）与良性腺泡相比，p27缺失仅在筛状周边细胞中显著，在融合性小腺泡中临界显著；（3）CD44v7/8在筛状周边细胞中表达缺失；其他比较无显著差异。ISH显示，筛状癌相对于良性腺泡有显著的PTEN缺失（P<0.02），而Gleason 3级癌或融合性小腺泡则没有。对于CDKN1B，各种癌症形态学之间的信号缺失程度不显著。总之，Gleason 4级癌的融合性小腺泡和筛状模式之间出现了分子差异。PTEN或p27缺失作为预后因素，在Gleason 4级癌的不同类型以及筛状结构中双表型周边与中央细胞群中需要进行不同的评估。
