Presence of cells in the polyaneuploid cancer cell (PACC) state predicts the risk of recurrence in prostate cancer

Abstract

Background:The nonproliferating polyaneuploid cancer cell (PACC) state is associated with therapeutic resistance in cancer. A subset of cancer cells enters the PACC state by polyploidization and acts as cancer stem cells by undergoing depolyploidization and repopulating the tumor cell population after the therapeutic stress is relieved. Our aim was to systematically assess the presence and importance of this entity in men who underwent radical prostatectomy with curative intent to treat their presumed localized prostate cancer (PCa). Materials and Methods: Men with National Comprehensive Cancer Network intermediate-or high-risk PCa who underwent radical prostatectomy l from 2007 to 2015 and who did not receive neoadjuvant treatment were included. From the cohort of 2159 patients, the analysis focused on a subcohort of 209 patients and 38 cases. Prostate tissue microarrays (TMAs) were prepared from formalin-fixed, paraffin-embedded blocks of the radical prostatectomy specimens. A total of 2807 tissue samples of matched normal/benign and cancer were arrayed in nine TMA blocks. The presence of PACCs and the number of PACCs on each core were noted.Results: The total number of cells in the PACC state and the total number of cores with PACCs were significantly correlated with increasing Gleason score (p = 0.0004) and increasing Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) (p = 0.004), but no other variables. In univariate proportional hazards models of metastasis-free survival, year of surgery, Gleason score (9-10 vs. 7-8), pathology stage, CAPRA-S, total PACCs, and cores positive for PACCs were all statistically significant. The multivariable models with PACCs that gave the best fit included CAPRA-S. Adding either total PACCs or cores positive for PACCs to CAPRA-S both significantly improved model fit compared to CAPRA-S alone. Conclusion:Our findings show that the number of PACCs and the number of cores positive for PACCs are statistically significant prognostic factors for metastasis-free survival, after adjusting for CAPRA-S, in a case-cohort of intermediate-or high-risk men who underwent radical prostatectomy. In addition, despite the small number of

Cells in the polyaneuploid cancer cell (PACC) state have increased metastatic potential

“…Presence of cells in the PACC state within primary tumors is generally associated with poorer prognosis [ 55 , 56 ]. Recently, it was shown that the presence of PACC state cells in the primary tumors of men with prostate cancer who underwent radical prostatectomy with curative intent is predictive of lower metastasis-free survival [ 57 , 58 ]. Additionally, rapid autopsy of 5 men with metastatic prostate cancer revealed presence of cells in the PACC state in all distant metastatic lesions analyzed [ 59 ].…”

Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues

“…L-DOXR cells exhibit increased genomic content (4N+) as compared to WT cells. The presence of cells with increased nuclear size and increased genomic content has been demonstrated to be associated with poor clinical outcomes in several types of cancers ( Alharbi et al, 2018 ; Amend et al, 2019 ; Fei et al, 2015 ; Imai et al, 1999 ; Liu et al, 2018 ; Lv et al, 2014 ; Mukherjee et al, 2022 ; O’Connor et al, 2002 ; Saini et al, 2022 ; Trabzonlu et al, 2023 ). We analyzed the occurrence of cells with increased nuclear size in human TNBC patients.…”

Polyploid Giant Cancer Cells Are Frequently Found in the Urine of Prostate Cancer Patients

“…This characteristic of PGCC has been reported in vitro in primary cultures of ovarian cancer [ 6 ] and in cell lines derived from leukemic cells [ 27 ]. It is thought to be involved in the origin of PGCC-derived proliferating tumor cells in patients with cancer recurrence [ 9 , 28 , 29 ]. Although it is difficult to definitively demonstrate PGCC budding by images of cells detected in biological liquids from patients, published studies clearly indicate this possibility [ 27 , 28 , 30 ].…”