K-ras Mutation Detection - Background Information
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Colon Cancer
Virtually 98% of all cancers in the large intestine are adenocarcinomas with a peak incidence between ages 60 and 79. Less than 20% of cases occur in patients less than 50 years old. There is no gender difference in the incidence of colon cancer.
Environmental factors, particularly dietary practices, are implicated in colon cancer and are believed to be effected by geographic location (higher death rates in US, Australia, New Zealand, and Eastern European countries and substantially lower death rates in Mexico, South America and Africa). Obesity and physical inactivity are also considered as risk factors for colon cancer.
Epidemiological studies showed that use of aspirin and other NSAIDs has protective effect against colon cancer. Lymph nodes, liver, lungs and bones are considered favoured sites of metastatic spread, followed by many other sites. In 25% to 30% of patients, the disease has spread beyond the range of curative surgery.
The extent of the tumor (tumor stage) at the time of diagnosis is the single most important prognostic indicator of colorectal carcinoma. Currently, most countries use the tumor-nodes-metastasis (TNM) classification and staging system from the American Joint Commission on cancer (Table 1).
TNM classification of Carcinoma of the Colon and Rectum (used for both clinical and pathologic staging)
Primary Tumor (T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ: intraepithelial or invasion of lamina Propria
T1
Tumor invades submucosa
T2
Tumor invades muscularis propria
T3
Tumor invades through the muscularis propria into the suberosa, or into non-peritonealized periocolic or perirectal tissues
T4
Tumor directly invades other organs or structures, and/or perforates visceral peritoneum
Regional Lymph Nodes (N)
Nx
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Metastasis in 1 to 3 lymph nodes
N2
Metastasis in 4 or more lymph nodes
Distant Metastasis (M)
Mx
Distant metastasis cannot be assessed
M0
No distant metastasis
M1
Distant metastasis
STAGE GROUPING
Stage
T
N
M
Dukes
MAC
0
Tis
N0
M0
-
-
I
T1
N0
M0
A
A
T2
N0
M0
A
B1
IIA
T3
N0
M0
B
B2
IIB
T4
N0
M0
B
B3
IIIA
T1-T2
N1
M0
C
C1
IIIB
T3-T4
N1
M0
C
C2/C3
IIIC
Any T
N2
M0
C
C1/C2/C3
IV
Any T
Any N
M1
-
D
American Joint Committee on Cancer, 2002, Cancer Staging Manual, Sixth Edition, page 115-116
K-ras Mutation Detection assay
During the last few years, clinical trials on colorectal cancer patients made discoveries related to personal genetic differences which could affect treatment regimens. Current studies showed that monoclonal antibodies against EGFR are not beneficial in patients with mutations in K-ras oncogenes. The most significant results indicated that successful treatment of metastatic colorectal cancer could be directly linked to the activation of K-ras signaling pathways.
Currently, there are different methods available to detect the K-ras mutations, from sequencing, mini-sequencing, using one-step polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis, to commercially available kits based on allele specific PCR (ARMS) and Scorpions® real-time PCR technology. MOUNT SINAI SERVICES (MSS) will use the K-ras Mutation Detection Kit based on ARMS and Scorpions® real-time PCR technology (www.dxsdiagnostics.com).
Links
There are many web sites issued by governments or societies which provide detailed information on colorectal cancer. The following list provides just few of these web sites:
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Mount Sinai Services 600 University Ave. Toronto, Ontario Canada M5G 1X5 |
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