Reason why FISH not necessary?

[*_Ginger_*]

Anyone know of reason why a FISH would not be needed to determine if really HER2 pos? The IHC of HER2 showed 2+ and I asked about getting a FISH done. Was told not needed. Is it because no recurrence yet?

[Esther]

I seem to remember that a FISH test was necessary when you are Her2+, since that could produce a different result than the IHC.

I believe that an IHC result of her2++, or her2+++ does not make a FISH test necessary.

Anybody know of anything different?

[Kristen]

Hello Ginger,
No, FISH testing is used to give information to your onc on where you are at with the overexpression at primary cancer. I can only tell you my experience with how my surgeon handled the test. My understanding is that there are 5 kinds of BC. ER+/PR+/HER2+/DNA and another one I can't remember. When I had my mastectomy, she ordered those tests. My IHC came in over 2, so she sent it out for a FISH analysis to see where my numbers were. What I was told is that routinely if an IHC test is over 2, they FISH test it. My FISH test came in at 7.6, which there is a range, but I don't know the numbers off the top of my head.
What my FISH path report said is this, "Results are expressed as the averaged ratio HER2 chromosome 17 signals in 60 nuclei.
Interpretation: Ratio of greater than 2.0 indicates HER2 gene amplification adjusted for for chromosome 17 polysomy. A site that will explain chrom17 is at www.ibms.org, search chromosome 17. Hope this helps. I pulled up this also on grading and there is a section down aways that talks about HER 2. Take Care, K

Histologic Grades of Breast Cancer: Helping Determine a Patient's Outcome Format for Printing

Main menu:

What is a histologic grade system?
Summary of Histologic Grades of Breast Cancer
Hormone Receptor Status
DNA Cytometry
Additional References and Resources

What is a Histologic Grade System?

Histology is the study of tissues, including cellular structure and function. Pathologists (physicians who conduct laboratory studies of tissues and cells) often assign a histologic grade to a patient’s cancerous breast tumor to identify the type of tumor present and help determine the patient’s prognosis (projected outcome). The Scarff-Bloom-Richardson system is the most common type of cancer grade system used today. To determine a tumor’s histologic grade, pathologists examine the breast cancer cells and their patterns under a microscope. A sample of breast cells may be taken from a breast biopsy, lumpectomy or mastectomy.

Pathologists closely observe three features when determining a cancer’s grade: the frequency of cell mitosis (rate of cell division), tubule formation (percentage of cancer composed of tubular structures), and nuclear pleomorphism (change in cell size and uniformity). Each of these features is assigned a score ranging from 1 to 3 (1 indicating slower cell growth and 3 indicating faster cell growth). The scores of each of the cells’ features are then added together for a final sum that will range between 3 to 9.

Tubule Formation (% of Carcinoma Composed of Tubular Structures) Score
> 75% 1
10-75% 2
less than 10% 3
Nuclear Pleomorphism (Change in Cells) Score
Small, uniform cells 1
Moderate increase in size and variation 2 2
Marked variation 3
Mitosis Count (Cell Division) Score
Up to 7 1
8 to 14 2
15 or more 3



Courtesy of the American Medical Association


Summary of Histologic Grades of Breast Cancer

A tumor with a final sum of 3, 4, or 5 is considered a Grade 1 tumor (well-differentiated). A sum of 6 or 7 is considered a Grade 2 tumor (moderately-differentiated), and a sum of 8 or 9 is a Grade 3 tumor (poorly-differentiated).

Grade Description Score 5 yr. survival 7 yr. survival

Grade 1
(lowest) Well-differentiated breast cells;
cells generally appear normal
and are not growing rapidly;
cancer arranged in small tubules. 3,4,5 95% 90%

Grade 2 Moderately-differentiated breast cells;
have characteristics between
Grade 1 and Grade 3 tumors. 6,7 75% 63%

Grade 3
(highest) Poorly differentiated breast cells;
Cells do not appear normal and tend to
grow and spread more aggressively. 8,9 50% 45%


*Scarff-Bloom-Richardson grade system

Pathologists also look for necrosis (areas of degenerating cancer cells) when determining a tumor’s grade. Cancers with a high grade, necrosis, cancers close to the surrounding margin of breast tissue of a lumpectomy sample, or large areas of DCIS are more likely to recur after breast cancer treatment than other breast cancers.(1)

Hormone Receptor Status

Physicians often examine hormone receptors in breast cancer cells at the time of biopsy or breast surgery to determine whether estrogen receptors (ER-positive) or progesterone receptors (PR-positive) are present. Patients whose cancers have ER or PR-positive receptors tend to have a better prognosis than patients whose cancers do not have these receptors. Cancers with ER or PR-positive receptors are also much more likely to respond to chemotherapy or hormone treatment.

Breast cancer cells that express ER-positive receptors in their nuclei also tend to respond better to hormonal manipulation. For example, the drug tamoxifen is used to block the female hormone estrogen from estrogen receptors, thus slowing the growth and reproduction of cancerous cells. Researchers know less about PR-positive receptors but have noticed that cells that contain ER-positive receptors often contain PR-positive receptors too. If a cell contains a PR-positive receptor but no ER-positive receptors, a patient’s prognosis may be worsened.

HER2 (human epidermal growth factor receptor 2), a protein receptor found on the surface of cells, is a key component in regulating cell growth. When the HER2 gene (sometimes written HER2/neu) is altered, extra HER2 receptors may be produced. This over-expression of HER2 causes increased cell growth and reproduction, often resulting in more aggressive tumor cells. HER2 protein over-expression affects 25% to 30% of breast cancer patients. A new drug, herceptin, has recently been approved by the U.S. Food and Drug Administration (FDA) to treat women with metastatic breast cancer who over-express HER2. Metastatic breast cancer is cancer that has spread past the breast and underarm lymph nodes.

Physicians may test tumor tissue for HER2 over-expression at the time of breast biopsy or surgery. Testing may also be done on stored tumor tissue from previous biopsy. To test for HER2 over-expression, the tumor tissue will be stained by a specific solution. A pathologist will then examine the tissue, checking for highlighted areas where high levels of over-expression are present. Depending on the level of staining, the tumor tissue sample may be classified as HER2 positive.

It is estimated that 200,000 HER2 diagnostic tests are performed each year. Women are encouraged to be tested for HER2 over-expression at the time of breast cancer diagnosis since results of the test may help determine a course of treatment.

DNA Cytometry

Cytometry is the process of counting and measuring a patient’s cells. DNA cytometry involves measuring a breast tumor’s DNA to help predict the tumor’s aggressiveness. Flow cytometry is one type of DNA cytometry in which lasers and computers are used to measure the amount of DNA in cancer cells suspended in liquid as they flow past a laser beam. A second type of DNA cytometry, image cytometry, involves using computers to analyze digital images of the cells from a microscope slide. Both flow cytometry and image cytometry measure the DNA ploidy (amount of DNA) of cancer cells. Ploidy is a marker that helps predict how quickly a cancer is likely to spread. Cancers with the same amount of DNA as normal cells are called diploid and those cancers with either more or less than that amount are called aneuploid. About two-thirds of breast cancers are aneuploid.(1) Several studies have shown that aneuploid cancers tend to be more aggressive than normal cancers.

Flow cytometry can also measure a tumor’s S-phase (the percentage of cells in a sample that are in the synthesis stage of cell division). Many cells in the S-phase indicate that the breast tissue is growing fast and that the cancer is likely to be more aggressive than normal cancers. Image cytometry can also estimate the growth rate of a cancer when combined with special antibody tests of the breast tissue.

[Kristen]

Ginger, one other thing. Don't let these prognosis figures scare you. No one knows for sure what our prognosis is because we are getting new combos' and have herceptin around. Even all the mets ladies on this board will tell you, they were given a "time" and they have proved them all wrong. Stay Strong and ask any quesions you want answered. TK, K

[Lisa]

All I know is that the FISH test is supposed to be more accurate in determining your HER2 status. If the lab still has your sample, just ask for it.

Love and light,

Lisa

[StephN]

Great question and good info posted by Kristen.

I did not have FISH as my IHC reported "poorly differentiated cells and high grade with Her2+++." So, I knew at the outset that I had an aggressive kind of tumor and proceeded into treatment on that basis.

Also, I am hormone neg/neg.

So, if there is any reason for a question ask for the FISH, otherwise if you get a very positive IHC that should be enough.

One other thing, The standard of care may have changed since my diagnosis nearly 4.5 years ago. Maybe FISH is the standard at some clinics after IHC shows HER2 pos.

[AlaskaAngel]

What I've read sounds like what you've read -- that anything less than HER2+++ on IHC isn't as reliable as FISH. My IHC results came out HER2+++ so were not tested by FISH. A lot can depend on it, so if in doubt, continue to ask about it.

A.A.

[*_Leslie_*]

Hi Ginger,
Having a HER2 status by IHC of 2+ is exactly the group that would benefit the most from the FISH test. A HER2 IHC status of 0 or 1+ is considered negative. A 3+ would be definately positive. It is the 2+ people who need to have the FISH test to determine if they really are HER2 amplified. The FISH test is considered more accurate. This enables the doctors to determine if Herceptin would be an effective line of defense. ( Being IHC 2+ and FISH positive would mean a positive result for overexpression, possibly being helped by Herceptin. IHC 2+ but FISH negative would be considered a negative result for amplification. Testing by FISH should not have anything to do with not having a recurrance.
Hope this helps.
Leslie

[Guest]

I was told by my oncologist even if you have a low or weak score for HER2 you are a HER2 positive. Fish test are more accurate than the IHC test and also more expensive. Push to have the FISH test done.