What are the characteristic's of colon cancer caused by HNPCC?
What advantages does early diagnosis have?
What are screening recommendations for HNPCC?
What protocols should be followed if an individual is identified as a carrier (or very likely a carrier)?
What testing for mutations in the MLH1 gene are available?
How may HNPCC be diagnosed in the future?

What are the characteristic's of colon cancer caused by HNPCC?

    Cancers for HNPCC patients are morphologically identical to other cancers, but HNPCC tumors tend to be more aggressive in their pattern of growth and differentiation (Ref. 8) . These characteristics are not quantitative, making it difficult to classify a cancer as sporadic or HNPCC. Guidelines have been written and modified to best define HNPCC: (Ref. 8)

• At least 3 relatives should have cancer of the large intestine, one should be a  first degree relative to the other two.
• At least two successive generations should be affected
• In one of the relatives, colorectal cancer should be diagnosed before age 55.

What advantages does early diagnosis have?
 

If detected in early stages there is a 90% survival rate. However, it is not often detected until late stages decreasing the survival rate to 35%. (Ref. 16) Therefore, anyone who has reason to suspect this disease is found in their family should be screened on a regular basis in order to increase chances of early stage detection. Screening is a very cost effective way for suspected carriers to monitor their health. It is widely under used at the present time, with only 20-30% of the general public screened according the to recommended guidelines. It is important for everyone to be screened regularly just because of the autosomal dominate nature of the disease coupled with its low survival rate in late stages.

 

What are screening recommendations for HNPCC? (Ref. 6)

• Baseline colonoscopy at age 50
• Annual digital rectal exam after age 40
• Stool blood testing annually after age 50
• Pap smears every two years for women
• Mammography every 1-2 years after age 40

• For asymptomatic carriers (Ref. 4):

• Colonoscopy* every 1-3 years beginning at age 20-25
• Adenomatous polyps should be removed during endoscopy
• Family members should be referred for genetic counseling

• For female carriers:

• Annual pelvic exam with endometrial aspiration** beginning at age 25-35
• Annual transvaginal pelvic ultrasound beginning at age 25-35

Endometrial aspiration: This test involves taking tissue and fluid samples from the lining to the uterus to detect the presence of cancerous cells.
 

What testing for mutations in the MLH1 gene are available?

    The test can run in the range from $700 to $2,000 and many insurance companies will not cover these charges.  Because of this, it is recommend that family history  of prospective test candidates and the meaning of the test results be analyzed by and discussed with a genetic counselor.  For information about genetic counseling, check the Cancer Control Site.

    Either a whole blood sample or fresh frozen tumor specimen can be analyzed for HNPCC.  However since there are many mutations in not only the MLH1 gene but the other genes that can cause HNPCC, it is often difficult to detect if the same gene has been inherited by other family members.

    If a patient is found to carry the normal gene, then he or she can be reassured that they do not have the HNPCC syndrome.  However this does not mean that their risk of cancer is zero, it means that their risk is the same as the general population.

    There have also been discoveries which now enable the theoretical determination of the risk of genetic colon cancer during embryogenesis.
 

How may HNPCC be diagnosed in the future?

    Tumors in patients with HNPCC show a feature called microsatellite instability (MSI).  It is currently unclear how useful testing for this will aide in the diagnosis of HNPCC.  Future medical advances and knowledge of HNPCC may result in diagnosis of HNPCC based on this anomaly.

    Currently, the presence of microsatellite instability in tumors of colon cancer patients is a good indicator that the person may be afflicted with HNPCC.