Was G(3+4) once a baby G(3+3)?

do the offspring of a Gleason 3+3 remain a 3+3, or do they morph into higher numbers? eg., A G(3+4) was once a baby G(3+3)?

[Could cancer cells that avoid apoptosis, start their lives as G9 and G10 or were they once baby G(3+3)s?]

I have seen articles mentioning that G3 and G4 cells are genetically different.

That would suggest that they would not progress, but perhaps another member will have a definitive answer.

halbert said...
I don't know a definitive answer. However, for surgical patients, a significant percentage of the time a G3+3 at biopsy turns into a 3+4 on surgical pathology. It just says a lot about how much we don't know.

But since there is often not a lot of time between Dx an surgery compared to how many years the cancer has been growing, I always figured that means the Bx just missed the G7. Or, diagnoses error as we so often see on those 2nd or 3rd opinions on the Bx results. Plus of course, sometime they are down graded. But who really knows?

I did see a study or two somewhere that was comparing the number of G6 vs G8-10 Dx in the pre PSA era vs after the era of PSA, or something like that. I'm don't remember exactly how they came to the conclusion, but I remember they strongly leaned towards a low risk stayed low risk, and high risk started out high risk.

Post Edited (BillyBob@388) : 3/5/2015 12:41:21 PM (GMT-7)

As you might suspect, we have had this conversation before. In fact, if you search "johns hopkins study organ confined" (without quotes) using the Search function at the top of this screen, upper right, you will get a listing of a number of very good discussions that we have had on this topic.

After retrieving and reviewing this listing myself, I found the following discussion particularly useful, with answers to your question:

www.healingwell.com/community/default.aspx?f=35&m=2396284

Highlights from that discussion:

OK, here's your answer. I just got off the phone with Dr Scholz for my yearly consult and asked him that question. He said that in most all cases a G6 remains a G6 and rarely progresses to a G7. What usually occurs is that a higher grade grows independently as another tumor starting off with the higher grade. So a G6 tumor can grow larger as time progresses, but it won't turn into a higher grade.

My docs agree that G-6 tumors don't necessarily progress into G-9 tumors over time. They seem to think the G-9 tumors develop as G-9 tumors right from the get-go

Also worthy of note:

For organ confined G6 PCA death is very-very-very rare. The last study I read showed that 3 out of 9,577 patients died after 15 years. That is a 99.97% survival rate. That study contained patients from 3 major medical centers. Johns Hopkins had a study with 2526 patients who had organ confined G6 PCA and nobody died up to 15 years out.

My own uro put it to me this way (and this is virtually a direct quote): "Prostate cancer is either a kittycat or a mountain lion. And if it's a kittycat it never grows into a mountain lion."

Technically, this question about whether or not a G6 can progress is still on the table, but the preponderance of evidence so far seems to indicate that a true G6 organ contained does not normally do so.

I think there are about 6 different questions being addressed in this thread:

1) Can a true Gleason Score 6 tumor metastasize?

This is the easiest question. The answer is decidedly no. This has been discussed in many previous threads, so I won't belabor it. I will add that GS 6 has also never been found with stage T3b, and only rarely and focally with stage T3a.

2) Can a Gleason score 6 tumor eventually become a Gleason score 7, 8, 9, or 10 tumor?

Probably. The tumor is an ecological system of interacting cells, so even a few cells of higher grade may eventually predominate, given the right circumstances. Many never progress to higher Gleason score.

3) Can a Gleason pattern 3 cell become a Gleason pattern 4 or 5 cell eventually?

Maybe. Once the genetic and epigenetic machinery is off kilter, genetic errors may (or may not) continue to accumulate. Researchers have found G4 cells with a common genetic signature to G3 cells, but whether it evolved sequentially or in parallel is uncertain.

4) Do all higher Gleason pattern cells start off at a lower grade pattern?

Probably not. There is evidence of parallel development, perhaps from a common ancestor prostate cancer stem cell.

5) How can we distinguish the GS 6 tumors that will remain indolent from the ones that will progress eventually?

Genetic (e.g., Prolaris and Oncotype Dx) and biochemical tests (e.g., TMPRSS2:ERG fusion) may give a clue.

6) How can we be sure from a biopsy that the tumor is indeed a GS 6 tumor?

We can't with absolute certainty, but the mpMRI-targeted/US fusion-guided biopsies in the hands of an excellent radiologist are getting really good at finding GS 7 or higher tumors. Saturation biopsies too, and CDUS in really expert hands. We gain certainty with such repeated biopsies.

- Allen

EPE=stage T3a in #1 above
Positive margins are in part due to surgeon skill.

Mjw,
A G6 can grow into the rectum or bladder if it gets large enough. This can cause substantial damage, but does not spread to other organs as higher grades of PC.

Prostate cancer is multi-focal. Upon biopsy of organs removed during surgery, the average number of tumors found is 7. Seven distinct, separate tumors. These tumors can be of different Gleason grades..12 core needle biopsies can miss one or more of these separate tumors and thereby give a false picture of the true Gleason grade..There can indeed be a Gleason 9 tumor lurking in a prostate gland that biopsied a Gleason 6....