A 50-year old male presents with large bowel type diarrhea and rectal bleeding. On sigmoidoscopy, a cauliflower-like growth is seen in the rectum. Colectomy specimen on histopathology shows adenocarcinoma. Which of the following prognostic investigations is not required?
Ans. c. EGFR mutations Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviours. It was observed that EGFR was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFT-targeted therapies (e.g. cetuximab), although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment."- Deng Y, Jurland B, Wang .1, Bi .1, Li W, Rao S, Lan P, Lin T and Lin E. High epidermal growth factor receptor expression in metastatic colorectal cancer lymph nodes may be more prognostic of poor survival than in primary tumor. Am J Clin Oncol. 2009;32:(3):245-52High EGFR expressions in metastatic lymph nodes seem to be more accurate in predicting survival than in primary or metastatic tissues. Microsatellite Instability: (Robbil,) The microsatellite instability pathway is characterized by genetic lesions in mismatched repair genes. It is involved in 10 to 15% of sporadic cases of colon cancer and in the hereditary non-polyposis colon cancer (HNPCC) syndrome. Mutations in the mismatch repair genes cause alternation of microsatellites, leading to microsatellite instability. These satellites are prone to misalignment during DNA replication. Most microsatellite sequences are in the non-coding regions of the genes, and hence, mutations in these genes are probably harmless. However, some microsatellite sequences are located in the coding or promotor regions of genes involved in regulation of cell growth. Loss of mismatch repair genes leads to accumulation of these and other growth-regulating genes, culminating in the emergence of colorectal carcinoma. C-MYC Mutations: In human colorectal adenocarcinomas, overexpression of the c-myc mRNA has been repoed to occur in 60-80% of cases. C-myc has been characterized as a proto-oncogene, which promotes cell proliferation. However, overexpression of the c-myc mRNA is associated with a more ourable prognosis. k-RAS mutations: The k-RAS is the most frequently observed activated oncogene in adenomas and colon cancers. k-RAS plays a role in intracellular signal transduction and is mutated in fewer than 10% of adenomas less than 1 cm in size, in about 50% of adenomas larger than I cam and in approximately 50% of carcinomas.
Microsatellite instability
c-myc mutations
EGFR mutations
k-RAS mutations