Intro: The Basics

Welcome to The Basics. In this section, we’ll go over all the first questions you may have about your colorectal cancer diagnosis. We’re going to discuss things like where your tumor is located, how far it has spread, and break down confusing topics like grade and stage.

This content is part of CRC101, a Learning Center with tons more information! In order to see the table of contents, look at the upper left hand corner of the page and click on one of the icons below:

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Last updated: November 13, 2022

Is my tumor MSS (pMMR) or MSI-H (dMMR)?

All newly diagnosed CRC patients should have their tumors tested for MSS/MSI status. Finding out which kind of tumor you have can have a big impact on what treatment options are available to you.

So what do those acronyms really mean? Learning about mismatch repair (MMR) is a great place to start.

There are two major types of colon cancer:

  • Microsatellite stable (MSS) or proficient mismatch repair (pMMR) is the “normal” state our cells are in, where the mismatch repair (MMR) pathway is active and functional. MMR is the body’s system for recognizing and repairing wrong letters in DNA synthesis. MSS is the most common kind of colon cancer.
  • Microsatellite instability (MSI) or deficient mismatch repair (dMMR) is the “mutant” state, where the MMR pathway is not working as usual. This is often called MSI-H for microsatellite instability high.

So what are microsatellites?

Microsatellites are short, repeated sequences in your DNA. They can vary in length between people, but within one person’s DNA they are a specific length. We can use this as a kind of “fingerprint” of someone’s DNA.

Here’s what they look like:

When your cells grow and divide, your DNA needs to replicate too. As we mentioned earlier, your body can make mistakes! So DNA mismatch repair enzymes — proteins with special jobs — come along and fix any errors. These enzymes are coded for in your DNA itself.

Now, there can be an issue where the enzymes used to repair your DNA are themselves defective. If this happens, those short repeated sequences, microsatellites, can accumulate errors in length and get wonky. If your microsatellites have these errors, your tumor is likely MSI-H.

How do I know if my MMR pathway is working normally?

Most cancer centers send a sample of your tumor, called a biopsy, to their pathology department for MMR studies using an immunohistochemistry (IHC) test. Through this process, doctors look at your tumor’s protein expression on microscope slides.

You might get a pathology report that says something like this:

MLH1: Intact nuclear expression (or expressed, positive or present)

MSH2: Intact nuclear expression (or expressed, positive or present)

MSH6: Intact nuclear expression (or expressed, positive or present)

PMS2: Intact nuclear expression (or expressed, positive or present)

This means your tumor is MSS. These acronyms (MLH1, MSH2, MSH6, PMS2) are all specific proteins involved in mismatch repair, and the report shows they are all present as they should be.

Your report might go on to say:

No loss of nuclear expression of MMR proteins (or negative or absent), low probability of MSI-H.

This statement also means that your tumor is MSS. When it says there’s a “low probability of MSI-H,” the report refers to the rare case where — despite having no loss of the MMR proteins — there can be a defect in the gene. For the great majority of people, the statement above means that they are MSS — even if the report does not explicitly state that!

You might also get a pathology report that looks like this:

MLH1: Intact nuclear expression (or expressed)

MSH2: Intact nuclear expression (or expressed)

MSH6: Loss of nuclear expression (or not expressed)

PMS2: Intact nuclear expression (or expressed)

This means that your tumor is MSI. Your pathology report might go on to say, for example: 

Loss of nuclear expression for MSH6 only. High probability of Lynch syndrome (tumor MSI evaluation and sequencing of germline MSH6 are indicated).

Lynch syndrome is a hereditary disease linked to a higher risk of cancer.

Want to learn more about Lynch syndrome?

Check out this link from the Mayo Clinic.

Don’t worry, we’ll talk more about Lynch syndrome later on.

So what does all of this mean for treatment?

The great majority of all CRC is MSS. About 85% of all-stage CRC and about 96% of stage IV CRC is MSS.

MSI makes up about 15% of all CRC and about 4% of stage IV CRC. The good news is that this subset of CRC can be treated with immunotherapy, which is very effective for some patients.

This is why it’s so important that everyone diagnosed with CRC knows whether their tumor is MSS or MSI!

Looking for more information about what MSS/ MSI-H status means for your treatment?

Come join us in Colontown!

  • In Tom’s MSI-H Clinic, you can learn all about clinical trials and treatment options specific to MSI-H patients
  • In Tom’s MSS Clinical Trials Clinic, you can learn about clinical trials open to MSS patients

Interested in joining? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: August 22, 2023

The Basics

What is the stage of my tumor?

Determining if your tumor has spread — and if so, how much it has spread — is known as staging. The lower the number, the less the cancer has spread. Although each person’s cancer experience is unique, cancers in the same stages often have a similar outlook, and are treated in similar ways.

For example, the best treatment for an early-stage cancer might be surgery or radiation, while later stages may require chemotherapy, targeted drug therapy, or immunotherapy.

Staging is determined by testing, including physical exams, imaging, endoscopies (such as a colonoscopy), biopsies and sometimes surgery. It’s important to know that cancer can be staged more than once. You might get a stage when you’re first diagnosed, but often staging is updated after treatment has started. This is known as restaging.

Stages are determined by three key pieces of information:

  • How far the cancer has grown into the wall of the colon or rectum
  • If the cancer has spread to any lymph nodes
  • If the cancer has metastasized, which means spread to distant organs

Take a look at what the wall of the colon looks like:

TNM system

The most common and useful staging is the TNM system.

In this system, the overall stage from I (one) to IV (four) is determined after the cancer is assigned a letter or number to describe the T (tumor), N (node) and M (metastasis) categories. 

Confusing, right? Let’s go over it again:

  • T describes the original tumor
  • N says whether the cancer has spread to any lymph nodes
  • M shows whether the cancer has spread (metastasized) to any other parts of the body
T: The primary tumor

When determining how much the cancer has spread, doctors first take a look at the primary tumor. This is where the cancer originated. The size, location, and growth into other areas are important to look at.

The T category is assigned a letter or a number:

  • TX means there is no information about the primary tumor, or it can’t be measured
  • T0 means there is no evidence of a primary tumor, and it can’t be found
  • Tis means that the cancer cells are only growing in the layer they started in, without spreading into deeper layers. This might also be referred to as in situ cancer or pre-cancer
  • T1, T2, T3 and T4 describe the tumor size and/or amount of spread into nearby areas. The higher the T number, the larger the tumor and/or the more it has grown
N: The lymph nodes

Many types of cancer spread into nearby lymph nodes before they reach other parts of the body. Your doctor will check to see if cancer has spread to them.

The N category is assigned a letter or a number:

  • NX means there’s no information about the lymph nodes near the tumor, or they can’t be assessed
  • N0 means nearby lymph nodes do not contain cancer
  • N1, N2 and N3 describe the size, location and/or number of lymph nodes affected by cancer. The higher the N number, the greater the spread
M: Metastasis

Cancer that has spread to body parts far away from the primary tumor is known as metastasis. 

The M category is assigned a number:

  • M0 means that no distant cancer spread has been found
  • M1 means that cancer has spread to other organs

Putting it all together

Adding these TMN categories together can give you your stage, broadly classified into stage I, II, III, and IV. 

You can use the chart below to determine which stage your cancer is:

For example, if your tumor is T3 N1 M0, you have stage III cancer.

Still a bit confused? Here’s an analogy:

Manju’s 7-year-old son just got back from his soccer game, and wanted to talk about his mom’s cancer.

Son: Mommy, I thought your cancer was stage IV.

Manju: No, it was stage III.

Son: What’s the difference?

Manju: My cancer was in the rectum —

Son: I KNOW! What does stage I mean? Tell me about that.

Manju: Okay… Your soccer socks have a pocket for your shin guards, right?

Son (feeling his shins): Yes, I feel 4 layers. My pants, the first layer of my sock, my shin guard, then the second layer of my sock. Then the skin of my leg. Why are you telling me this?

Manju: Wait for it. This is a very simple explanation, okay? The wall of the colon and rectum are just like your soccer uniform, they have many different layers. If the tumor is like a small rock stuck between your skin and the inner sock layer, it’s stage I. If the rock is a bit bigger, and pokes into the inner sock layer and shin guard, it’s more like stage II.

Son: And if it’s like a bigger rock, poking through the inner sock layer, the shin guard, and into the outer sock layer, that’s stage III?

Manju: Yes, you’ve got it! And stage IV is when the tumor goes through all the layers — AND can be found in some other part of the body.

Son: Like in your knee?

Manju: Like in the liver or lungs, up here.

Son: Oh, okay. So your tumor was really stage III. I get it now!

Want to chat with other people in the same stage as you?

Join one of our COLONTOWN Facebook groups:

  • 1st Avenue (Stage I patients)
  • 2nd Avenue (Stage II patients)
  • 3rd Lane (Stage III patients)
  • Four Corners (Stage IV patients)
  • NEDS Ballroom (Patients with current or past NED — no evidence of disease — status)

Interested in joining? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: May 18, 2022

What is the grade of my tumor?

The differentiation, also known as grade, of your cancer describes how abnormal the tumor cells look under a microscope. Cancers that are higher grade (poorly differentiated) tend to grow quickly. 

If your oncologist hasn’t mentioned grade, that’s okay! Many different factors play a role in cancer diagnosis and treatment. If you have any questions, reach out to your healthcare team.

CRC is often divided into 3 grades:

  • Well differentiated (low grade)
  • Moderately differentiated (intermediate grade)
  • Poorly differentiated (high grade)

A bit confusing, right? Take a look at the picture below. As differentiation deteriorates, cancer cells start looking wonky.

So why does this matter?

The grade of your tumor can tell you how likely your cancer is to spread, but other factors, such as the stage and genetic profile of your tumor, are important to consider when determining prognosis.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: May 18, 2022

Where is my tumor located?

When you eat food, the body breaks it down and extracts the nutrients you need through the digestive system.

The digestive system starts in the mouth and is made up of the esophagus, stomach, small intestine, colon (also known as the large intestine), rectum, and anus. The small intestine’s main job is to absorb nutrients from your food. The colon’s main job is to reabsorb water and minerals from your poop.

The colon can be broken down into even smaller parts:

  • The cecum, the beginning of the colon where the small intestine empties into the large intestine
  • Ascending colon
  • Transverse colon
  • Descending colon
  • Sigmoid colon

The colon ends at the rectum, where poop is stored until it is excreted through the anus.

So why does this matter?

Knowing what side of the colon your tumor is on is an important consideration. Right-sided colon cancer is found in the cecum, the ascending colon and the transverse colon. Left-sided colon cancer comprises tumors in the descending colon or sigmoid colon. Rectal cancer means that they primary tumor is in the rectum and anal cancer means that the primary tumor is located in the anus.

Tumors in the right and left colon have different characteristics, and may have different treatment plans. Rectal and anal cancer may have different treatment protocols depending on your diagnosis. For example, rectal tumors often require radiation before surgery, whereas colon tumors do not. 

Want to learn more about sidedness or tumor location?

Join one of our COLONTOWN Facebook groups:

  • On the Right Side (Cancer in the cecum, ascending, or transverse colon)
  • Rectalburgh (Rectal cancer)
  • Small Bowel Corral (Small intestine cancer)
  • Analwise (Anal cancer)

Want to join? Fill out the registration form here.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: May 18, 2022

What is colorectal cancer?

Our bodies are made up of about 30 trillion cells that together form our tissues and organs. As the body grows and ages, these cells go through trillions of replications and divisions.

Behind the wheel of all this complex growth and division is our DNA, the instruction manual that tells cells how to make and do everything they need to do.

Sometimes this genetic code gets errors.

Most of the time, the body’s highly effective proofreading system goes through and fixes these errors. But sometimes, they’re left unchecked. The resulting cells, which often grow at unexpected and dangerous rates, can become tumors.

When a tumor develops in the colon or rectum, we call this colorectal cancer (CRC).

Want to learn more about how cancer develops in the body?

Check out this link from the National Cancer Institute, where you can find more information.

COLONTOWN University has so much more to offer, from DocTalk videos with CRC experts to easy-to-understand biomarker test breakdowns. We’re here for you! See our list of Learning Centers here.

Last updated: October 27, 2022