PROGNOSTIC SIGNIFICANCE OF IMMUNOHISTOCHEMISTRY AND PROLIFERATIVE ACTIVITY IN COLORECTAL CANCER USING SURVIVIN, COX2, S PHASE FRACTION AND DNA PLOIDY.
- Pathology Department, Faculty of Medicine, Zagazig University, Egypt.
- Surgery Department, Faculty of Medicine, Zagazig University, Egypt
- Medical Biochemistry Department, Faculty of medicine, Zagazig University, Egypt.
- Cite This Article as
- Corresponding Author
Background:- Aggressiveness of neoplasm may be linked to the biological characteristic of tumor cells, represented by the level of expression of specific molecular markers. Aim: was to examine the co-expression of survivin, COX-2, DNA ploidy and S phase fraction (SPF) in colorectal carcinomas and assess its prognostic value. Material and Methods:- neoplastic tissue from 100 patients with primary non treated colorectal adenocarcinomas were assessed by immunohistochemistry and flow cytometry. Statistical analysis evaluated the correlation of marker expression with clinicopathological variables and with the expression of other markers. Results:- Survivin and COX-2 cytoplasmic immunoreactivity was detected in 65% and 73% respectively of the studied adenocarcinomas. Flow cytometry revealed that 62% of carcinomas were aneupliod and 47% had high SPF. COX-2, DNA aneuploidy and high SPF showed significantly association with lymph nodes (LN) involvement and Dukes’ stage (P = 0.04, P = 0.02 and 0.03, respectively for LN and P = 0.03, P = 0.01 and 0.04, respectively for Dukes’ stage). DNA aneuploidy was positively associated with histological grade (P = 0.03). High SPF and DNA aneuploidy were positively associated with tumor localization (P = 0.03 for both). COX-2 displayed positive association with survivin expression and with recurrence (P = 0.04 and P = 0.02 respectively). High SPF significantly associated with survivin, COX-2 and DNA ploidy (P = 0.005, P = 0.004 and 0.02, respectively). The expression of more markers by each carcinoma was positively correlated with LN involvement (P = 0.04) and advanced stage (P = 0.001). Conclusions: Our analysis demonstrate that the score of markers co-expression correlates significantly with the poor prognosis of patients with colorectal adenocarcinomas.
- Friedlich MS, Stern HS. Primary prevention: what can you tell your patient? Surg Oncol Clin N Am 2000; 9:655-60; discussion 61-3.
- Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61:759–67.
- Boo YJ, Park JM, Kim J, Chae YS, Min BW, Um JW, Moon HY. L1 expression as a marker for poor prognosis, tumor progression, and short survival in patients with colorectal cancer. Ann Surg Oncol 2007; 14:1703–11.
- Feezor RJ, Copeland EM, 3rd, Hochwald SN. Significance of micrometastases in colorectal cancer. Ann Surg Oncol 2002; 9:944–53.
- Soumaoro LT, Uetake H, Higuchi T, Takagi Y, Enomoto M, and Sugihara K.Cyclooxygenase-2 Expression: A Significant Prognostic Indicator for Patients with Colorectal Cancer. Clinical Cancer Research 2004; 10: 8465–8471.
- Salzano G, Riehle R, Navarro G, Perche F, De Rosa G, Torchilin VP. Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: a promising strategy to overcome drug resistance in cancer, Cancer Lett. 2014 Feb 28;343(2):224-231
- Wang J, Li Z, Lin Z, Zhao B, Wang Y, Peng R, Wang M, Lu C, Shi G, Shen Y. 17-DMCHAG, a new geldanamycin derivative, inhibits prostate cancer cells through Hsp90 inhibition and survivin downregulation, Cancer Lett. 2015 Jun 28; 362(1):83-96.
- Athanasoula KCh, Gogas H, Polonifi K, Vaiopoulos AG, Polyzos A, Mantzourani M. Survivin beyond physiology: orchestration of multistep carcinogenesis and therapeutic potentials, Cancer Lett. 2014 Jun 1;347(2):175-182
- Qiu Y , Find all citations by this author (default). Or filter your current search Li X , Find all citations by this author (default). Or filter your current search Yi B , Find all citations by this author (default). Or filter your current search Zheng J , Find all citations by this author (default). Or filter your current search Peng Z , Find all citations by this author (default). Or filter your current search Zhang Z , Find all citations by this author (default). Or filter your current search Wu M , Find all citations by this author (default). Or filter your current search Shen F , Find all citations by this author (default). Or filter your current search Su C. Protein phosphatase PHLPP induces cell apoptosis and exerts anticancer activity by inhibiting survivin phosphorylation and nuclear export in gallbladder cancer, Oncotarget 2015, 6(22):19148-19162.
- Pennati M1, Folini M, Zaffaroni N. Targeting survivin in cancer therapy, Expert Opin. Ther. Targets 12 (2008) 463–476.
- Fux R, Schwab M, Thon KP, Gleiter CH, Fritz P. Cyclooxygenase-2 Expression in Human Colorectal Cancer Is Unrelated to Overall Patient Survival. Clin Cancer Res. 2005 Jul 1; 11(13):4754-60.
- Dario C. Altieri. Targeting survivin in cancer, Cancer Lett. 2013 May 28; 332(2): 225–228.
- de Leval X1, Delarge J, Somers F, de Tullio P, Henrotin Y, Pirotte B, Dogné JM. Recent advances in inducible cyclooxygenase (COX-2) inhibition. Curr Med Chem 2000; 7:1041–62.
- Prescott SM, Fitzpatrick FA. Cyclooxygenase-2 and carcinogenesis. Biochim Biophys Acta 2000; 1470:M69–78.
- Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M and Hla T. Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 1995; 55: 3785–3789
- Kargman SL, O’Neill GP, Vickers PJ, Evans JF, Mancini JA and Jothy S. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 1995; 55: 2556–2559.
- Kawamori T, Rao CV, Seibert K and Reddy BS. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998; 58: 409–412
- Salud A, Porcel JM, Raikundalia B, Camplejohn RS and Taub NA. Prognostic Significance of DNA Ploidy, S-Phase Fraction, and P-Glycoprotein Expression in Colorectal Cancer. Journal of Surgical Oncology 1999;72:167–174
- Quirke P, Dixon MF, Clayden AD, Durdey P, Dyson JE, Williams NS, Bird CC .: Prognostic significance of DNA aneuploidy and cell proliferation in rectal adenocarcinomas. J Pathol 1987; 151:285–291.
- Lanza G, Gafà R, Santini A, Maestri I, Dubini A, Gilli G, Cavazzini L. Prognostic significance of DNA ploidy in patients with stage II and stage III colon carcinoma. A prospective flow cytometric study. Cancer 1998; 82:49–59.
- Sarela AI, Macadam RCA, Farmery SM, Markham AF, Guillou PJ. Expression of the anti-apoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma. Gut 2000; 46:645– 650.
- Lu C-D, Altieri DC, Tanigawa N. Expression of a novel antiapoptosis gene, survivin, correlated with tumour cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 1998; 58: 1808–12.
- Sarela AI, Scott N, Ramsdale J, Markham AF, Guillou PJ. Immunohistochemical Detection of the Anti-Apoptosis Protein, Survivin, Predicts Survival After Curative Resection of Stage II Colorectal Carcinomas. Annals of Surgical Oncology 2001; 8(4):305–310
- Masunaga R, Kohno H, Dhar DK, Ohno S, Shibakita M, Kinugasa S, Yoshimura H, Tachibana M, Kubota H, Nagasue N. Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients. Clin Cancer Res. 2000 Oct; 6 (10):4064-8.
- Hedley DW, Friedlander ML, Taylor IW, Rugg CA, Musgrove EA: Method for analysis of cellular DNA content of paraffin embedded pathological material using flow cytometry. J Histochem Cytochem 1983; 31: 1333-1335.
- Taylor SR, Zachariah S, Chakraborty S, Overstreet J, Ramzy L, Mody DR. Ploidy studies by image analysis on fine needle aspirates of the breast. Acta Cytol 1993; 37:923-928.
- Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 1998; 58:5071– 4.
- Suga K, Yamamoto T, Yamada Y, et al. Correlation between transcriptional expression of survivin isoforms and clinicopathological findings in human colorectal carcinomas. Oncol Rep. 2005; 13:891–897.
- Sarela, AI, Scott, N, Ramsdale J, Markham AF, and Guillou PJ. Immunohistochemical Detection of the Anti-Apoptosis Protein, Survivin, Predicts Survival After Curative Resection of Stage II Colorectal Carcinomas. Annals of Surgical Oncology, 2001:8(4):305–310.
- Kalliakmanis JG, Kouvidou Ch, Latoufis C, Kouvatseas G, Anagnostakis D, Papatheodoridis G, Koskinas J, Archimandritis A. Survivin Expression in Colorectal Carcinomas: Correlations with Clinicopathological Parameters and Survival. Dig Dis Sci (2010) 55:2958–2964.
- Endo T, Abe S, Seidlar HB, et al. Expression of IAP family proteins in colon cancers from patients with different age groups. Cancer Immunol Immunother. 2004; 53:770–776.
- Al-Maghrabi J, Buhmeida A, Emam E, Syrjanen K, Sibiany A, Al-Qahtani M and Mahmoud Al-Ahwal: Cyclooxygenase-2 expression as a predictor of outcome in colorectal carcinoma. World J Gastroenterol 2012. 2012 Apr 21; 18(15): 1793–1799.
- Joo YE, Kim HS, Min SW, Lee WS, Park CH, Park CS, Choi SK, Rew JS and Kim SJ: Expression of cyclooxygenase-2 protein in colorectal carcinomas. Int J Gastrointest Cancer 2002: 31: 147-154.
- Elzagheid A, Emaetig F, Alkikhia L, Buhmeida A, Syrjänen K, El- Faitori O, Latto M, Collan Y, Pyrhönen S. High cyclooxygenase-2 expression is associated with advanced stages in colorectal cancer. Anticancer Res 2013; 33: 3137-3143.
- Soumaoro LT, Uetake H, Higuchi T, Takagi Y, Enomoto M, Sugihara K: Cyclooxygenase-2 expression: a significant prognostic indicator for patients with colorectal cancer. Clin Cancer Res 2004;10: 8465-8471,.
- Sheehan KM, Sheahan K, O’Donoghue DP, et al. The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 1999; 6:282:1254–7.
- Dean PA, Vernava AM III. Flow cytometric analysis of DNA content in colorectal carcinoma. Dis Colon Rectum 1992; 35:95– 102.
- Pinto AE, Chaves P, Fidalgo P, et al. Flow cytometric DNA ploidy and S-phase fraction correlate with histopathologic indicators of tumor behavior in colorectal carcinoma. Dis Colon Rectum 1997; 40:411–419.
- Bazan V1, Migliavacca M, Zanna I, Tubiolo C, Corsale S, Calò V, Amato A, Cammareri P, Latteri F, Grassi N, Fulfaro F, Porcasi R, Morello V, Nuara RB, Dardanoni G, Salerno S, Valerio MR, Dusonchet L, Gerbino A, Gebbia N, Tomasino RM, Russo A. DNA Ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study. J Cancer Res Clin Oncol (2002) 128: 650–658.
- Salud A, Porcel JM, Raikundalia B, Camplejohn RS, Taub NA. Prognostic significance of DNA ploidy, S-phase fraction, and P-glycoprotein expression in colorectal cancer. J Surg Oncol 1999; 72:167–174
- Ito T1, Shiraki K, Sugimoto K, Yamanaka T, Fujikawa K, Ito M, Takase K, Moriyama M, Kawano H, Hayashida M, Nakano T, Suzuki A. Survivin promotes cell proliferation in human hepatocellular carcinoma. 2000 May; 31(5):1080-5.
- Kawasaki H1, Toyoda M, Shinohara H, Okuda J, Watanabe I, Yamamoto T, Tanaka K, Tenjo T, Tanigawa N. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis. 2001 Jun 1; 91(11):2026-32.
- Sarela AI1, Verbeke CS, Ramsdale J, Davies CL, Markham AF, Guillou PJ. Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma. Br J Cancer. 2002 Mar 18; 86(6):886-92.
- Mrena J1, Wiksten JP, Kokkola A, Nordling S, Ristimäki A, Haglund C. COX-2 is associated with proliferation and apoptosis markers and serves as an independent prognostic factor in gastric cancer. Tumour Biol. 2010 Jan; 31(1):1-7. doi: 10.1007/s13277-009-0001-4. Epub 2009 Dec 18.
- Yamagishi M1, Noda M, Tatsumi Y, Mukaisho K, Mitsufuji S, Sugihara H, Okanoue T, Hattori T. Correlation between cyclooxygenase-2, proliferative activity, and mucin phenotype in human advanced gastric cancer. J Gastroenterol. 2004 Dec; 39(12):1143-9.
- Yu J1, Leung WK, Ebert MP, Ng EK, Go MY, Wang HB, Chung SC, Malfertheiner P, Sung JJ. Increased expression of survivin in gastric cancer patients and in first degree relatives. Br J Cancer. 2002 Jul 1;87(1):91-7.
- Barnes N1, Haywood P, Flint P, Knox WF, Bundred NJ. Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence. Br J Cancer. 2006 Jan 30; 94(2):253-8.
- Yang Y1, Zhu J, Gou H, Cao D, Jiang M, Hou M. Clinical significance of Cox-2, Survivin and Bcl-2 expression in hepatocellular carcinoma (HCC). Med Oncol (2011) 28:796–803.
[Walid S. H. Elsayed, Samah S. Elbasateeny, Rasha S. H. Elsayed, Ibtsam S. Harera and Rehab S Abdul-Maksoud. (2017); PROGNOSTIC SIGNIFICANCE OF IMMUNOHISTOCHEMISTRY AND PROLIFERATIVE ACTIVITY IN COLORECTAL CANCER USING SURVIVIN, COX2, S PHASE FRACTION AND DNA PLOIDY. Int. J. of Adv. Res. 5 (2). 441-453] (ISSN 2320-5407). www.journalijar.com
Pathology Department, Faculty of Medicine, Zagazig University, Egypt.
Article DOI: 10.21474/IJAR01/3169 DOI URL: http://dx.doi.org/10.21474/IJAR01/3169
Share this article
This work is licensed under a Creative Commons Attribution 4.0 International License.