Abstract 2025: Inverse relation of Myc and p27 in cribriform pattern prostate cancer
Authors: Kulac Ibrahim , Hicks Jessica , Zheng Qizhi , Fedor Helen , Cornish Toby C. , De Marzo Angelo M. 
Published: August 2015

Background: Prostate cancers composed exclusively of Gleason pattern 3 have an excellent prognosis,while those containing Gleason pattern 4 or higher are more aggressive. Gleason pattern 4 is composed of either fused glands, poorly formed glands or cribriform structures with cribriform structures being most readily recognized and shown to be of independent prognostic significance (PMIDS: 24145642;25189638). However, the biological properties of these cribriform structures have not been studied. There is a spectrum of nuclear features in cribriform glands with cells towards the perimeter containing enlarged nucleoli, and open chromatin as compared to cells towards the center. Since MYC overexpression drives nucleolar enlargement we examined the pattern of expression of MYC protein in these structures. Also, we examined p27 staining since it has been reported to be more intense in the nuclei in the center of these structures (PMID:9731735).

Design: Cases with cribriform Gleason score 7 were used for IHC for MYC, p27 and Ki67 as well as double label immunofluorescence staining for p27 and MYC. Slides were scanned and regions were selected containing cribriform glands (N = 18 total regions) and analyzed using image analysis software by Aperio Inc. We quantified the level of nuclear staining for MYC and p27 in relation to the outside/perimeter regions versus the inner aspect of the glands. Chromogenic in-situ hybridization for MYC mRNA was also performed.

Results: The increase in MYC staining in the perimeter aspects of the cribriform structures was highly significant as compared to the inner regions (P&lt;0.0001, rank sum). Conversely, p27 staining showed an increase in the central region as compared to the perimeter aspect (P = 0.0024). There was also a marked increase in staining for Ki67 (p&lt;0.0001) as well as MYC mRNA in the perimeter cells. Double label fluorescent staining showed a tight inverse correlation between MYC and nuclear p27 staining.

Conclusion: Two distinct populations of cancer cells comprise cribriform carcinomas of the prostate; the central aspect is composed of cells with relatively small nucleoli that are non-proliferating with high levels of nuclear p27, and an outer layer that is composed of metabolically more active cells with increased MYC, nucleolar size and proliferative fraction. These findings provide new biological insights into the unique structure of cribriform prostate cancer lesions and suggest a complex interplay between the two cell types. Future studies are needed to determine how and whether these findings relate to disease aggressiveness.

Citation Format: Ibrahim Kulac, Jessica Hicks, Qizhi Zheng, Helen Fedor, Toby C. Cornish, Angelo M. De Marzo. Inverse relation of Myc and p27 in cribriform pattern prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2025. doi:10.1158/1538-7445.AM2015-2025