Tumor Progression: Adenoma Carcinoma Sequence – Carcinogenesis

by Carlo Raj, MD

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    00:01 The flow chart here, you will notice that we completed quite a bit. And before we move on, I want to show you as to how much progress you have made. You walked through all the different chemicals, radiation and viruses that are responsible for carcinogenesis. You have talked about DNA repair and how if that goes rye may result in carcinogenesis. Also talked about inactivation of tumor suppressor gene, activation of oncogene. We just completed our discussion of quickly how to evade apoptosis.

    00:31 We talked quite a bit so does'nt this flow chart now seem a hack of a lot more manageable. Where are we now? We are going to increase the proliferation. We are going to progress the tumor further. So therefore, just to make sure we're clear understand the following. So you have proliferation taking place. Proliferation takes place, hyperplasia. You are moving towards cancer. What's the next step after hyperplasia that is a little bit or a lot more dangerous. It's called dysplasia. And whenever you have dysplasia if you pathologically, the term in which we will talk about alot, not to worry. That nucleus that is oh so very important for proliferation. If you are worried about cancer, now that nucleus is referred to as being atypical. Atypical nucleus in pathology means that oh my goodness, I have a cell that is about, it' on the brink of going on to cancer.

    01:33 Now once cancer sets in, or malignancy sets in, can the membrane still be intact? Yes it can. You call that in-situ.

    01:43 In-situ is a malignancy in which the membrane is intact. Very simple as far as you are concerned. Eventually what may happen? Progression then you metastasis. Let's first talk about the progression. First we will do adenoma-carcinoma sequence.

    02:01 Understand the topic. We are moving from benign neoplasia into malignant neoplasia and then finally we have staging an invasion and rupture the membrane and metastasis. The prototype for this will be colorectal cancer. Quickly, you should be thinking about APC on chromosome 5. If this then gets mutated then yout APC can no longer control whom? Beta catenin. You have increase activity of what biochemical process? Transcription, good. And you have increased proliferation. Is that the only mutation? Not necessarily.

    02:38 The mucosa is at risk, keep going. Then, this adenoma which has been formed which means what? Increased proliferation. Other mutations can also exist including K-RAS. Others also mutated include p53. Also know SMAD, or SMAD-2. Finally, if there is increased multifactorial type of mutations, at some point maybe telomerase activity is enhanced. What's telomerase activity? Oh my goodness, the tumor cell has found fountain of youth. Something that Johnny Depp was looking for in Pirates of The Caribbean but was never able to find. But the cancer cells were actually successful. What does telomerase mean to you? Fountain of youth.

    03:30 No matter how much damage takes place in DNA the telomerase activity is going to then keep the DNA intact. Hence read please.

    03:41 Telomerase are found in most genes that are carcinoma. You also notice now that this polyp, if it's a villous type.

    03:50 Don't worry about what type right now. The point is, if there is increased proliferation increased mutations, you are going to have invasion through the submucosa, mucosa. You'll pass through the membrane and then off to the races unfortunately.

    04:05 And this spread could be either lymphatic which carcinoma love. And then maybe perhaps hematogeneous through your portal vein.

    04:11 Where are you headed? Liver. Carcinogenesis, escape from immunity. Why would your cancer cell want to be killed by immune cell.

    04:25 Loss of immune function. Just a couple of things here. The immunosurveillence normally destroys neoplastic cells via recognition of 'nonself' antigens. Both the humoral and the CMI will play a role. And patients with immune system dysfunction, often times have an increased risk for neoplasia. Keep that in mind. We see that clinically quite a bit. Staging.

    04:48 What you will be responsible from now until the end of the pathology course will be just a simple staging that you are responsible for where the prognosis might be pretty decent to begin with. And then with a particular stage, your prognosis drops like crazy.

    05:06 For example, renal cell carcinoma. With renal cell carcinoma between stages let's say, 2 and 3 you might then invade through the capsule.

    05:17 Once you invade through the capsule, in renal cell carcinoma, you have entered the renal vein. Metastasis. Towards where? Well, towards the inferior vena cava. Are we clear? The staging mechanism is called T, Tumor; N, number of lymph nodes; M, will be metastasis. I'll keep coming back to this.

    About the Lecture

    The lecture Tumor Progression: Adenoma Carcinoma Sequence – Carcinogenesis by Carlo Raj, MD is from the course Cellular Pathology: Basic Principles with Carlo Raj.

    Included Quiz Questions

    1. The cancer is confined within the basement membrane.
    2. The malignancy has invaded local tissues.
    3. The tumor has metastasized.
    4. The malignancy has progressed through the basement membrane.
    5. The malignancy has spread to local lymph nodes.
    1. It keeps the malignant DNA intact for further replication.
    2. It creates monoclonality.
    3. It provides the "second hit" in the gene mutation.
    4. It predisposes a patient to further proto-oncogene mutations.
    5. It allows for hematogenous spread.
    1. Metastasis
    2. Tumor size
    3. Number of lymph nodes involved
    4. Number of tumors
    5. Location of lymph nodes involve (local vs distant)

    Author of lecture Tumor Progression: Adenoma Carcinoma Sequence – Carcinogenesis

     Carlo Raj, MD

    Carlo Raj, MD

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