open access (pdf): Endometrial cancer genomics and genetics (of interest to Lynch Syndrome women/dual malignancies eg. ovarian/uterine cancers)

Endometrial cancer genomics and genetics


Abstract: (click on pdf for full file)

Most sporadic endometrial cancers (ECs) can be histologically classified as endometrioid, serous, or clear cell.

Each histotype has a distinct natural history, clinical behavior, and genetic etiology. Endometrioid ECs have an overall favorable prognosis.

They are typified by high frequency genomic alterations affecting PIK3CA, PIK3R1, PTEN, KRAS, FGFR2, ARID1A (BAF250a), and CTNNB1 (β-catenin), as well as epigenetic silencing of MLH1 resulting in microsatellite instability.

Serous and clear cell ECs are clinically aggressive tumors that are rare at presentation but account for a disproportionate fraction of all endometrial cancer deaths. Serous ECs tend to be aneuploid and are typified by frequent genomic alterations affecting TP53 (p53), PPP2R1A, HER-2/ERBB2, PIK3CA, and PTEN; additionally, they display dysregulation of E-cadherin, p16, cyclin E, and BAF250a.  

The genetic etiology of clear cell ECs resembles that of serous ECs, but it remains relatively poorly defined. A detailed discussion of the characteristic patterns of genomic alterations that distinguish the three major histotypes of endometrial cancer is reviewed herein.

open access: Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist’s initiative

Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist’s initiative

"....One limitation of our study was the low response rate in the eligible patients. This may have biased our results, especially if the surgeons had consciously avoided recruiting patients with a (very) poor prognosis or emotional problems. Such bias would have resulted in underestimation of psychological distress. At present, we cannot assess whether bias was present. However, we note that in our sample, the levels of psychological distress were lower than those described in the literature. 

Another reason for the low response rate may have been the complex logistic inclusion procedure [15], if communication of the test result to the patient exceeded the inclusion criterion of 6 months. In some cases, it took several months before the MSI-test report, written by the pathologist, was sent to the surgeon and a number of weeks more before the patient was contacted. Another limitation of our study was that no firm conclusions could be drawn, because the large number of tests increased the possibility of a type I error, which we have not corrected for. 

Despite some methodological concerns, we can conclude that moderate levels of distress were present following MSI testing in patients recently diagnosed with CRC. These levels were similar to those in other patients diagnosed with CRC [27, 47, 48]. 

High cancer-specific distress was observed in 40% of the MSI-positive patients and was significantly correlated with female gender."

Australia - Cancer Directory - Lynch Syndrome booklet (pdf file - updated Jan 25, 2012)

Understanding genetic tests for Lynch syndrome. Information and decision aid

Year first published or reviewed: 2010
Last updated on: 25-01-2012
By: Centre for Genetics Education

 

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Lynch syndrome cancers
People affected by Lynch syndrome have a higher risk of bowel cancer
and some other cancers listed in the table below.

Men with Lynch syndrome are at
high risk of developing:
large bowel cancer

Women with Lynch syndrome are
at high risk of developing:
large bowel cancer
endometrial cancer
ovarian cancer

Men and women have an
increased risk of developing:
cancers of the stomach, small
bowel, kidney, brain, pancreas,
ureter (tube from kidney to
bladder