Page 138 - Read Online

Ambe et al. Mini-invasive Surg 2018;2:37 I http://dx.doi.org/10.20517/2574-1225.2018.45 Page 3 of 13

Table 1. Amsterdam II criteria and revised Bethesda criteria
Type Description
Amsterdam II criteria 1. Three or more relative with a Lynch - associated malignancy (gastrointestinal cancers,endometrial
cancer, ureter or renal pelvic cancer)
2. Two or more successive generations involved including involvement of a first-degree relative
3. At one individual is diagnosed before the age of 50 years
4. Familial adenomatous polyposis has been ruled out
Revised Bethesda criteria 1. Colorectal cancer diagnosed in a patient less than 50 years of age
2. Synchronous or metachronous colorectal cancer or other Lynch tumor independent of age
3. Colorectal cancer with MSI-H diagnosed in a patient less than 60 years of age
4. Colorectal cancer diagnosed in one or more first-degree relative with a Lynch-related tumor, one
of which is diagnosed on or before the age of 50 years
5. Colorectal cancer diagnosed in two or more first or second-degree relativen with Lnych-related
tumors regardless of age
MSI-H: high level of microstatellite instability

in the proximal colon. However, both old age and left-sided or rectal cancers are far more frequent than
originally described, since more systematic detection and a more unbiased approach have been pursued.
Histopathologically, HNPCC tumors are usually large, mutinous, poorly differentiated and exhibit an ex-
[9]
tensive lymphocytic infiltration . Despite these unfavorable histopathological features, HNPCC tumors
[10]
rarely metastasize and are therefore associated with a better prognosis compared to sporadic CRC .
The clinical diagnosis of HNPCC is based on the patient’s personal and family history. The Amsterdarm II
[12]
criteria and the revised Bethesda criteria [Table 1] still remain the most common approach for iden-
[11]
tifying potential Lynch patients or families, despite their poor sensitivity and specificity. Histopathologic
examination of tumor biopsies obtained during colonoscopy including immunohistochemical staining for
gene products of the MMR genes represents a simple and cost-effective method of identifying individu-
als with MMR deficiency requiring an individualized therapeutic approach. Of these, approximately 30%
[13]
will harbour a constitutional mutation, that leads to the diagnosis LS . Therefore all patients with the
substantial family history and/or MMR deficiency in the tumor (biopsy) require genetic counseling and if
consented genetic testing in a DNA sample in normal tissue.

Recently, it has been demonstrated that systematic tumor testing without previous staining for loss of pro-
tein expression renders a more efficient approach. The authors conclude that “up-front tumor sequencing in
colorectal cancer is simpler and has superior sensitivity to current multitest approaches to Lynch syndrome
screening, while simultaneously providing critical information for treatment selection” . Also, germline
[14]
testing in unselected CRC cases with a gene panel [25 known predisposing genes for gastrointestinal tract
(GI) cancers] rendered a yield of nearly 10% of identified carriers with a pathogenic mutation. These recent
results indicate the need to reassess the value of systematic panel testing either in the tumor or in consti-
tutional DNA as a preferred method for identification of patients with hereditary conditions, rather than
staining for MMR deficiency, also taking into account that the polyposis syndromes are almost all stable
(exception PPAP and MSH3 polyposis). Specifically for a tailored surgical approach, it is of increasing im-
portance to be aware of the risk disposition for subsequent cancers.

Individuals with a confirmed pathogenic mutation benefit from a regular surveillance program, although
the value of each screening procedure must be weighed against potential harm and to date there is a lack of
evidence for some of the recommendations. Also, there is no global agreement on the intervals and type of
procedures or quality assurance. Beside this, additional data has evolved indicating that a more differenti-
[15]
ated approach on the basis of the different MMR genes and gender is required .
The indications for colorectal surgery in patients with HNPCC are basically similar to those in patients
with sporadic CRC. Premalignant polyps with severe dysplasia, large polyps not amendable via colonos-