A question about differences between Gleason scores and cell mutations

Following this one because Uro said something very disturbing at hubby's 4 month post op visit. On biopsy he had one G7 but on surgical path was downgraded to G6. However, last week at the visit uro stated "You had fairly aggressive cancer". Since when is G6 aggressive cancer? From everything I've read G6 doesn't metastasis. It goes along w/ the question you're asking so I'll wait for the experts to weigh in on this one.

Hi Miki,

Hmm, I'd be confused by what your husband's doctor said as well. We were told that G6 is not aggressive, and G7 (which turned out to be by father's score after the biopsy) was termed "intermediary" by the doctor performing the biopsy.

Migration= a propensity for a definitively graded cell to morph into a higher graded cell. A definition I will use for this discussion. For my purposes migration has nothing to do with cancer spreading thru the body..by my definition of the word.The question as to whether a definitive gleason 6 or any definitive gl grade can migrate to a higher gl grade is one that is controversial in the pca medical community. No one as yet, to my knowledge, has solved this issue. Studies have shown that Gl 6 rarely metastasizes, which would leave one to think migration does not exist, at least this is a false argument that folks use routinely. I accept that a gl6 rarely metastasize. This in no way says anything as to whether they can migrate to a grade that does metastasize There are no studies to my knowledge that suggest cells do not migrate upward and possibly downward{the latter I doubt}. I personally believe they do. This does not mean that clusters of cells do not "bloom" as an already established grade 5 or less. It simply means that I believe , given time, any pca cancer cell can Migrate{refer to my definition} . It could be, however that any gl grade present may never migrate but instead fertilize the garden for spontaneous higher gl grades to present themselves in time. I could actually argue for both sides of the argument logically… this in itself just feeds the controversy, and buttresses the reality that PCa is such a mysterious disease. Of all the cancers this is the one that, who's genesis will be the most difficult to find. Having said that, strides in pca treatment gives hope. It is always better to get the cause, so as to eradicate it completely. Sadly this will be difficult to do. But hopefully the treatments will more and more morph the disease into a chronic rather than an acute disease. The real question is what in fact causes dis ease{ not a pun on the word, but part of the words origin}. Ya know like disciple and discipline for instance. Or ignore and ignorance as another example.
Mimi, Your uro either did not have his notes on your case or felt he in some way that he needed to "justify" himself after the downgrade, by saying he had a aggressive disease. Bottom line It was removed with excellent pathology, Gl 6 is indeed the least aggressive and yours is indeed a gl with little chance of migration, if they do in fact migrate at all. A side note on this post: As I was typing this I noticed how difficult it was to express my thoughts using the various words... as the proprietary ones could all be used differently…which then led to a thought that how difficult it is of any of us to really communicate truly our thoughts, especially when in todays paradigm, there is a propensity to distrust intent rather then receive wording trust. I, {recently} , for those who know me here know different} have been trying to, by my words transform the words of others ,when ever I sense this distrust. Its amazing to me how the sensory touch…. that the word Trust symbolizes….. can indeed be so heartfelt... as to be able to transform the others distrust into trust. I seek this and I trust it will be found.{Hold me to it} Thanks again for letting me share who I am….. PS Remember….Realization…not Recognition edit and any self assumption that is implied.

Miki,

The word "aggressive" doesn't, as far as I know, have a particularly specific definition when applied to cancer and it's not particularly odd to apply it to low-Gleason disease. It simply suggests that the cancer, if left untreated, would have been likely to have caused problems, eventually. Higher Gleason cancers cause problems by circulating in the blood stream and causing distant mets. They can be hard to treat since they tend to pack up and flee surgery and radiation like Oakies fleeing the dust bowl. Gleason 6 disease moves to the 'burbs and "aggressive" Gleason 6 disease does so en masse and tends to sprawl into other nearby tissues. With six positive cores on biopsy and with a tumor that represented something like a third of the gland your husband's Gleason 6 disease could probably be fairly described as "aggressive". He's well rid of it.

Gleason score is an indicator of the amount of cell "dysplasia" going on. Dysplasia means the normal cell architecture now looks different. It looks different because the cells' genetics are different. As cancer progresses, the cells are less differentiated (i.e., they function less like normal prostate cells) and become more stem-cell like in character. They may be spun off from "cancer stem cells", or cloned with mutations from earlier versions, or both.

The less differentiated they are, the more aggressive they are. Gleason grade 3 (G3) cells are incapable of living outside of the prostatic environment because they are still very similar to healthy prostate cells. (One can't graft healthy prostate tissue to, say, skin tissue in an attempt to grow a new prostate). In contrast, G4s and G5s are often able to survive outside of the prostate. They have undergone a genetic transition (called EMT) that allows them to become mobile in the serum and lymph and plant themselves in other tissues.

I really like PDA's okies/suburban sprawl analogy.

- Allen

arthur-qa said...
Tall Allen, when you write "the more aggressive they are", you mean less differentiated cells tends to travel, clone and mutate at a faster rate, than lower Gleason scales?

Right.

arthur-qa said...
the more one waits or delays, the higher the probability for more genetically mutated cells, thus the higher probability of hormone-resistance disease...

"Waits or delays" to do what? If the cells have metastasized, it's already too late for curative treatment.

arthur-qa said...
Oh, I meant delaying treatment at this stage...

What kind of treatment are you talking about, and what stage are you talking about?

No one delays primary treatment with a high risk diagnosis, for example, and if you are talking about secondary treatments, it depends on what they are. For example, it is not at all clear that early hormone therapy after, say, RP and salvage RT when there are no metastases provides any survival benefit.

Because you asked this question, I assume you are facing some kind of decision. It might be better if you fully described your situation rather than trying to generalize. PC does not lend itself to generalizations.

- Allen

I'm sorry to hear this bad news.

So he never had any initial treatment, other than a single round of HT, after his Dx in 2000? Why do you call it a "remission?" Ten years from Dx to mets is part of the long natural history of the disease - it's actually on the briefer side of the curve. It sounds like that he had one of the varieties of PC that do not put out a lot of PSA. That's part of the reason I said that PC doesn't lend itself to generalizations.

It's very common with intermittent ADT to get a great response to the first cycle and progressively lesser responses to subsequent cycles. It's not called "castrate resistance" until the PSA actually rises while on ADT, but, as you say, the cancer is certainly not as hormone responsive as it once was. I think replacing Casodex with Xtandi was a good move and hope it works for him.

You didn't say how many mets were discovered, but if there were several, I would urge you to talk to his oncologist about early use of docetaxel. Another point worth considering is treatment of the prostate (with RP or RT), which even at this late date, might slow down progression. Many mets are spread from the original tumor site if it isn't removed. There are also many clinical trials that he might benefit from.

- Allen

TA and PDA,
Thank you for the explanation. I learn so much from reading these threads. I think it would be great if all men understood what a psa test and Gleason score was all about. Seems that PCa should be broken down into two categories: pc G 6 or lower and pc G 7 +
Beth for Gary

Beth,

Like all things about PC, it's more complicated than it at first seems. Actually it has been suggested that dividing line be drawn a little higher than you suggest. Anthony D'Amico, the doctor who devised the basis for the most popular risk stratification criteria (the NCCN risk categories), has been advocating to draw the line between GS 3+4 and GS 4+3. He reasons that GS 3+4 behaves more like low risk PC, and is amenable to treatment by active surveillance, surgery and radiation monotherapies. GS 4+3 has a prognosis that is more like high risk PC, and is better treated with combination radiation therapies (or wider margins with SBRT) with added ADT. The probability of success of surgery for GS 4+3 depends on the staging (less than T3) more than anything.

The reason why GS 4+3 is so much more aggressive than GS 3+4 is because the tumor environment has an effect above and beyond the grade of the cells that compose it. The tumor is an ecological system of interacting cell types.

All of this applies to tumors in the prostate only, and before initial therapy. The OP did not mention that his father's situation was that he'd had a prostatectomy (including info like that in a signature would be helpful). Post prostatectomy, there are additional considerations that are prognostic for judging the cancer's aggressiveness.

- Allen

logoslidat,

You mentioned "Migration= a propensity for a definitively graded cell to morph into a higher graded cell." I am not sure if that is completely correct. From what I remember individual cells rarely switch (mutate) to a more aggressive or less aggressive form of cancer. But that (eukaryotic) cells when they undergo mitosis (cell division or replication) then mutation can occur. These mutations include additions, deletions and substitutions of DNA nucleotide sequence. Mutations can change the sequence of proteins which can have negative consequences such as promoting cancer or no effect depending where the mutation occurs (junk DNA snippet) Additionally mutations can be beneficial and without DNA mutations evolution would not exists.

logoslidat,

I posed the question to our director of pathology and one of the doctors where I work at (medical/dental school). The pathologist said she isn't aware of cells mutating themselves but only when mitosis occurs (most vulnerable time.) She did mention that factors such as radiation, viruses, chemicals, etc., can damage the cells causing mutations to occur during cell division. The doctor said the same thing but thought that it might be possible for a cell to mutate due to these previously mentioned factors prior to division. If that is the case, then I would reason that three things may happen, either the cell dies, or it is unable to divide due to this damage, or it can pass on the damage during division.

Nick