Immunohistochemical analysis of K-RAS expression in curatively treated colorectal cancer patients: Correlations of clinicopathological features with clinical outcome
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The study was conducted to assess the relationship between the presence of K-RAS oncogene expression in samples of colorectal carcinomas (CRC) and the clinicopathological data of investigated patients.
One hundred patients (55 females/mean age 64.55 years) with curable CRC treated during period 1/1/2000–31/12/2006 were studied. Eligibility criteria for cases included diagnosis with first primary incident CRC, age up to 75 years, and mental competence. Patients with distant metastasis, severe concomitant disease, coexistent malignancy, ulcerative colitis or Crohn’s disease, familial adenomatous polyposis, or immediate severe complication or death were excluded. The tumours concerned adenocarcinomas at TNM stages 0-I (26 patients), II (46 patients), and III (28 patients). Eighty-seven patients received chemotherapy, chemoradiotherapy or radiotherapy. All tumour specimens were reviewed for immunohistochemistry. Expressions of K-RAS and secondarily P53 were identified, and intensity/distribution was evaluated. All clinicopathological parameters were recorded. The cross-tabulation technique was used for variance analysis. P-values ≤0.05 were considered statistically significant.
At 5-year-follow-up, 11 deaths had occurred (stages II:4, III:7) among 20 recurrences (N1:8, N2:2). Deaths were associated with moderate (3 patients), moderate-intense (2 patients) and intense (6 patients) K-RAS staining (p=0.008), and with invasiveness of the tumour (p=0.0089), lymphnode metastasis (p<0.0001) and worse tumour differentiation (p<0.0001). A statistical significance was revealed among the general population between K-RAS intense staining and both worse tumour differentiation (p=0.0066) and N1 lymph-node metastasis (p=0.0469). A statistical significance between K-RAS and P53 expressions in women with T3 tumours was also noted (p=0.0387).
K-RAS overexpression correlated well with worse differentiation, lymph-node metastasis and invasive histologic mode in CRC.
Key wordsK-RAS Oncogene Colorectal cancer Immunohistochemistry
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- 2.Morrin M, Kelly M, Barrett N, Delaney P. Mutations of Ki-ras and p53 genes in colorectal cancer and their prognostic significance. Gut 1997;35:1127–1131Google Scholar
- 12.Zlobec I, Molinari F, Kovac M, Bihl MP, Altermatt HJ, Diebold J, Frick H, Germer M, Horcic M, Montani M, Singer G, Yurtsever H, Zettl A, Terracciano L, Mazzucchelli L, Saletti P, Frattini M, Heinimann K, Lugli A. Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients. Br J Cancer 2010;102:151–161PubMedCrossRefGoogle Scholar
- 20.Mahdavinia M, Bishehsari F, Verginelli F, Cumashi A, Lattanzio R, Sotoudeh M, Ansari R, Semeraro D, Hormazdi M, Fakheri H, Rakhshani N, De Lellis L, Curia MC, Cama A, Piantelli M, Malekzadeh R, Iacobelli S, Mariani-Costantini R. P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K-ras mutations. J Cell Physiol 2008.216:543–550PubMedCrossRefGoogle Scholar
- 24.Gervaz P, Bouzourene H, Cerottini JP, Chaubert P, Benhattar J, Secic M, Wexner S, Givel JC, Belin B. Dukes B colorectal cancer: distinct genetic categories and clinical outcome based on proximal or distal tumor location. Dis Colon Rectum 2001;44:364–372, discussion 372–373PubMedCrossRefGoogle Scholar
- 30.Scartozzi M, Mandolesi A, Giampieri R, Pierantoni C, Loupakis F, Zaniboni A, Galizia E, Giustini L, Silva RR, Bisonni R, Berardi R, Biagetti S, Menzo S, Falcone A, Bearzi I, Cascinu S. Insulin-like growth factor 1 expression correlates with clinical outcome in K-RAS wild type colorectal cancer patients treated with cetuximab and irinotecan. Int J Cancer 2010;127(8):1941–7.PubMedCrossRefGoogle Scholar
- 31.Tai CJ, Lee CH, Chen HC, Wang HK, Jiang MC, Su TC, Shen KH, Lin SH, Yeh CM, Chen CJ, Yeh KT, Chang CC. High nuclear expression of phosphorylated extracellular signal-regulated kinase in tumor cells in colorectal glands is associated with poor outcome in colorectal cancer. Ann Diagn Pathol 2012. doi:pii: S1092-9134(12)00129-3. 10.1016/j.anndiagpath.2012.09.004. [Epub ahead of print]Google Scholar
- 34.Scartozzi M, Giampieri R, Maccaroni E, Mandolesi A, Giustini L, Silva R, Zaniboni A, Biscotti T, Biagetti S, Galizia E, Loupakis F, Falcone A, Bearzi I, Cascinu S. Analysis of HER-3, insulin growth factor-1, nuclear factor-kB and epidermal growth factor receptor gene copy number in the prediction of clinical outcome for K-RAS wild-type colorectal cancer patients receiving irinotecancetuximab. Ann Oncol 2012;23(7):1706–1712. Epub 2011.PubMedCrossRefGoogle Scholar
- 35.Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008;359:1757–1765PubMedCrossRefGoogle Scholar