Unless you majored in cellular biology, there’s a good chance you never came across the word ploidy. The term refers to the number of complete sets of chromosomes in a cell. Chromosomes are composed of DNA molecules, which carry your genetic instructions. You wouldn’t be who you are without long chains of DNA packed into your chromosomes.

In humans, the normal set of chromosomes is 23 pairs, totaling 46 chromosomes (23 x 2 = 46). At the time of conception, you received one single set (23 chromosomes) from your mother’s ovum (egg), and the other set (23 chromosomes) from your father’s sperm. Since the germ cells (ovum and sperm) each have one chromosome set, they are called haploid cells. But as soon as the two sets pair up, they are called diploid. These chromosome-paired diploid cells now begin to multiply and form an embryo—the FUTURE YOU! Thus, humans are made up of diploid cells. The cells are programmed with copy mechanisms designed to duplicate the chromosome sets as cells reproduce themselves (“daughter cells”).

However, nature doesn’t always go as planned. When a cell is in the reproduction process, various errors can delete or duplicate specific chromosomes, leading to daughter cells with less or more than the normal number of 46. These are called aneuploid cells, and they can deviate in functionality from diploid cells. Aneuploidy has been found to exist in normal cells, though it’s not known if it contributes in some beneficial manner to the cell, or whether the cell is simply tolerating it.

When gene mutations spawn cancer cells, just like normal cells they can be either diploid or aneuploid. According to Orr, et al. (2015), “The role of aneuploidy in tumor initiation, progression, and recurrence has been the subject of controversy for many years.”^[i] Even so, ploidy matters. Renowned PCa pathologist Dr. David Bostwick notes, “Patients with diploid tumors have a more favorable outcome than those with aneuploid tumors.”^[ii] He points out that ploidy correlates with Gleason grade: the higher the grade at the time of diagnosis or treatment, the greater likelihood that the PCa cells are aneuploid. Thus, aneuploidy in prostate cancer (PCa) cells is linked with aggression and higher risk of recurrence after PCa treatment. Therefore, the ploidy of a patient’s PCa cells may act as a biomarker to predict the risk of recurrence.

In fact, a newly published paper by Pulk, et al. (2023) conducted a study of prostatectomy patients to test whether ploidy is an accurate prognosticator of biochemical recurrence (rising PSA) after surgical gland removal. If the risk were identified at the time of surgery, why wait till PSA starts to rise further down the line? “There is a need for an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population.”^[iii]Since ploidy can be obtained from the post-surgery prostate specimen, could it not be used to “red-flag” patients so potentially life-saving or life-extending salvage treatments could be initiated at the earliest possible time?

For this study, 99 patients who underwent prostatectomy between 2003-2009 were followed annually or until biochemical recurrence. At the time of surgery, the specimens’ tissues with worse Gleason patterns were analyzed for ploidy using a method called image cytometry which accurately identifies ploidy abnormalities. The authors noted a significantly higher presence of aneuploid PCa cells in patients whose pre-treatment PSA and Grade Group classified them as higher risk. They concluded, “DNA ploidy is an independent prognostic marker of BCR in low-risk PCa after radical prostatectomy, which could early on identify potentially aggressive PCa recurrences and introduce a more personalized approach to salvage treatments.”

This is not a new idea. Three years earlier, a Norwegian paper suggested ploidy as a “prognostic marker for the risk stratification of prostate cancer patients.”^[iv] In fact, back in 2009 a team of Johns Hopkins researchers proposed that ploidy could “serve as a surrogate biomarker that has the potential to replace biopsy Gleason scores for organ vs. non-organ confined PCa prediction.”^[v] PCa cell ploidy is easy to obtain when biopsy needle samples are sent for pathology lab analysis, though it is not routinely done. Dr. Bostwick himself has been proponent of ploidy analysis for risk stratification since the late 1990s.

Perhaps it’s worth considering the inclusion of ploidy in PCa pathology reports. It could be a relatively inexpensive adjunct to the classic determinants of risk level, and perhaps an indication of need for further genomic testing for known high-risk mutations. Another way of approaching this would be to ask, “Is there such a thing as too much information when developing an individualized PCa treatment strategy?” Just something to think about…

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Orr B, Godek KM, Compton D. Aneuploidy. Curr Biol. 2015 Jun 29;25(13):R538-42.
[ii] Bostwick D, Cheng L. “Neoplasm of the Prostate.” In Urologic Surgical Pathology (Fourth Edition). Elsevier, 2020. Pp. 415 ff.
[iii] Pukl M, George M, Javanmardi A, Carraro A et al. DNA Ploidy as a Potential Adjunct Prognostic Marker of Low-Risk Prostate Cancer Progression after Radical Prostatectomy. Urol J. 2023 Jul 22.
[iv] iv Ersvaer E, Hveem TS, Vlatkovic L, Brennhovd B, Kleppe A, Tobin KAR, Pradhan M, Cyll K, Waehre H, Kerr DJ,
Danielsen HE. Prognostic value of DNA ploidy and automated assessment of stroma fraction in prostate cancer. Int J Cancer. 2020 Aug 15;147(4):1228-1234.
[v] Isharwal S, Miller MC, Epstein JI, Mangold LA, Humphreys E, Partin AW, Veltri RW. DNA Ploidy as surrogate for biopsy gleason score for preoperative organ versus nonorgan-confined prostate cancer prediction. Urology. 2009 May;73(5):1092-7.