Comparative immunohistochemical study of proliferation and apoptosis in colorectal adenocarcinoma

Authors

  • M. A. Shyshkin Zaporizhzhіa State Medical University,

DOI:

https://doi.org/10.14739/2310-1237.2016.3.87497

Keywords:

intestinal neoplasms, adenocarcinoma, colon, rectum, cell proliferation, apoptosis, tumor suppressor protein p53, caspase-3

Abstract

Colorectal cancer is the actual problem in the global health care system, which is associated with high rates of morbidity and mortality.

Aim. To compare the expression levels of immunohistochemical markers of proliferation and apoptosis in the colorectal tumor cells and the colorectal tumor-associated stroma; to study the correlations between the proliferation levels, apoptosis levels and clinicopathological parameters of colorectal adenocarcinoma.

Materials and methods. The surgical material of 30 patients with distal colon adenocarcinoma (I-IV clinical stages) was analyzed using pathohistological and immunohistochemical methods.

Results. It was established that colorectal tumor cells are characterized by the medium proliferation level, the medium p53 expression level and the low apoptosis level, just as colorectal tumor-associated stroma is characterized by the low proliferation, p53 expression and apoptosis levels. The direct strong correlations between the proliferation and apoptosis levels in the tumor cells, and also between the proliferation and apoptosis levels in the tumor-associated stroma were revealed. The direct medium correlations between the p53 expression levels in the tumor cells and the tumor-associated stroma, between the p53 expression level in the tumor cells and the Ki-67 expression level in the tumor-associated stroma, and also between the p53 expression level in the tumor cells and the degree of histological differentiation of the tumor were revealed. Moreover, the reverse strong correlations between the Ki-67 expression levels and the caspase-3 expression levels in the tumor cells and the tumor-associated stroma were revealed.

Conclusions. These data indicate the tight association between proliferative and apoptosis processes in the colorectal tumor cells and the colorectal tumor-associated stroma. The interconnections between the p53 accumulation in the tumor cells and the colorectal tumor-associated stroma, the p53 accumulation in the tumor cells and the increase of proliferative activity of the colorectal tumor-associated stroma, and also between the p53 accumulation in the tumor cells and the degree of histological differentiation of the tumor were established. Furthermore, it was revealed that increase of proliferative activity of colorectal adenocarcinoma is associated with decrease apoptotic activity of the tumor.

References

Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015) Global Cancer Statistics, 2012. CA: A Cancer Journal for Clinicians, 65, 87–108. doi: 10.3322/caac.21262.

Kumar, V., Abbas, A. K., Fausto, N., & Aster, D. K. (2014) Osnovy patologii zabolevanij po Robbinsu i Kotranu [Robbins and Cotran Pathologic Basis of Disease]. Moscow: Logosfera [in Russian].

Fletcher, C., D. (2013) Diagnostic histopathology of tumors. Philadelphia: Elsevier Saunders.

Ingolf, J., B., Mavrova, R., Moga, S., Radosa, J., Schmidt, G., Rainer, M., B., et al. (2014) Can Ki-67 Play a Role in Prediction of Breast Cancer Patients' Response to Neoadjuvant Chemotherapy? BioMed Research International, 2014, 71–78. http://dx.doi.org/10.1155/2014/628217.

Inwald, E. C., Klinkhammer-Schalke, M., Hofstädter, F., Zeman, F., Koller, M., Gerstenhauer, M., & Ortmann, O. (2013) Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Research and Treatment, 139(2), 539–552. doi: 10.1007/s10549-013-2560-8.

Tumanskiy, V. A., & Chepets, A. V. (2016) Sravnitel´naya immunogistokhimicheskaya kharakteristika e´kspressii receptorov e´strogena-α i progesterona, p16 i p53, Ki-67 i kaspazy-3 v invazivnoj e´ndometrioidnoj adenokarcinome tela matki i v proliferativnom e´ndometrii [Comparative immunohistochemical characteristics of expression of estrogen receptors-alpha, progesterone receptors, p16, p53, Ki-67 and caspase 3 in invasive endometrial adenocarcinoma and normal proliferative endometrium]. Pathologia, 1(36), 22–28. [in Ukrainian]. doi: 10.14739/2310-1237.2016.1.72165.

Guo, Z. L., Chen, K., Wang, X. Q., & Hu, W. (2011). Expression and relationship of Ezh2, Runx3 and caspase-3 in endometrial adenocarcinoma. Zhonghua Bing Li Xue Za Zhi, 40(6), 387–391.

Nassar, A., Lawson, D., Cotsonis, G., & Cohen, C. (2008). Survivin and Caspase-3 Expression in Breast Cancer: Correlation with Prognostic Parameters, Proliferation, Angiogenesis, and Outcome. Applied Immunohistochemistry & Molecular Morphology, 16(2), 113–120. doi: 10.1097/PAI.0b013e318032ea73.

Heshiki, W., Tomihara, K., Yamazaki, M., Arai, N., Nakamori, K., & Noguchi, M. (2015). Constitutive Activation of Caspase-3 in Non-Apoptotic Oral Squamous Cell Carcinoma Cells. Journal of Cancer Science & Therapy, 7, 75–80.

Melling, N., Kowitz, C., M., Simon, R., Bokemeyer, C., Terracciano, L., Sauter, G., et al (2016). High Ki67 expression is an independent good prognostic marker in colorectal cancer. Journal of Clinical Pathology, 69, 209–14. doi: 10.1136/jclinpath-2015-202985.

Claudio, M. J., Ulysses, R. J., Kleber, Venancio, A., Vincenzo, P., Massad, E., Abraao, S., W., et al. (2012). Prognostic Predictive Factors in Colorectal Adenocarcinoma with Liver Metastasis. Scientific Reports, 9, 56–60.

Najib, R., Daoudi, K., Fatima, Z., H., Arifi, S., & Mellas, N. (2014). Ki 67 as a marker of prognosis in Morocco colorectal cancer. Annals of Oncology, 25, 153–156. doi: 10.1093/annonc/mdu165.195.

Mogoantă, S. S., Vasile, I., Totolici, B., Neamţu, C., Streba, L., Busuioc, C., J., & Mateescu, G., O. (2014). Colorectal cancer – clinical and morphological aspects. Romanian Journal of Morphology and Embryology, 55, 103–110.

Streba, L., ForŢofoiu, M. C., Popa, C., Ciobanu, D., Gruia, C. L., Mogoantă, S. Ş., & Streba, C. T. (2015). A pilot study on the role of fractal analysis in the microscopic evaluation of colorectal cancers. Romanian Journal of Morphology and Embryology, 56, 191–96.

Li, X., Zhou, J., Chen, Z., & Chng, W. (2015). p53 mutations in colorectal cancer - molecular pathogenesis and pharmacological reactivation. World Journal of Gastroenterology, 21(1), 84–93. doi: 10.3748/wjg.v21.i1.84.

Noble, P., Vyas, M., Al-Attar, A., Durrant, S., Scholefield, J., & Durrant, L. (2015). High levels of cleaved caspase-3 in colorectal tumour stroma predict good survival. British Journal of Cancer, 108, 2097–2105. doi: 10.1038/bjc.2013.166.

Gurzu, S., Jugn, J., Mezei, T., & Pavai, Z. (2007). The correlation between the immunostains for p53 and Ki67 with bcl-2 expression and classical prognostic factors. Romanian Journal of Morphology and Embryology, 48(2), 95–99.

Sobin, L. H., Gospodarowicz, M. K., & Wittekind, C. (2009) International Union Against Cancer (UICC). TNM Classification of Malignant Tumours. New York: Wiley-Blackwell.

Dabbs D. J. (Ed.) (2010). Diagnostic Immunohistochemistry. Philadelphia: Saunders/Elsevier.

Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., et al. (2015) The Human Protein Atlas. Retreved from: http://www.proteinatlas.org.

Tumanskyi, V. O., Yevsieiev, A. V., Kovalenko, I. S., & Zubko, M. D. (patentee) (2015) Patent 99314 Ukraina, MPK 2015.01 G01N 21/00 G06K 9/00 Sposib fototsyfrovoi morfometrii imunohistokhimichnykh preparativ [Patent of Ukraine 99314, IPC 2015.01 G01N 21/00 G06K 9/00 The technique of digital morphometry of immunohistochemical slides]. Biuleten, 10 [in Ukrainian].

Shyshkin, M. A. (2016) Osobennosti immunogistokhimicheskoj e´kspressii markera kletochnoj proliferacii Ki-67 v opukholevykh i stromal´nykh kletkakh kolorektal´noj adenokarcinomy [Immunohistochemical study of Ki-67 expression in the tumor cells and the stromal cells of colorectal adenocarcinoma]. Pathologia, 2(37), 76–81. [in Ukrainian]. doi: 10.14739/2310-1237.2016.2.80898.

Hegazy, A., Daoud, S. A., Ibrahim, W. S., El-Atrebi, K., Saker, M., & Abdel-Wahab, N. (2014) Role of Ki-67, P53 and Bcl-2 in Advanced Colorectal Carcinoma (Histopathological and Immunohistochemical Study). Academic Journal of Cancer Research, 7(3), 168–72. doi: 10.5829/idosi.ajcr.2014.7.3.1111.

Flanagan, L., Meyer, M., Fay, J., Curry, S., Bacon, O., Duessmann, H., et al. (2016). Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach. Cell Death and Disease, 7, 2087–2098. doi: 10.1038/cddis.2016.7.

Alcaide, J., Funez, R., Rueda, A., Perez-Ruiz, E., Pereda, T., Rodrigo, I., et al. (2013). The role and prognostic value of apoptosis in colorectal carcinoma. BMC Clinical Pathology, 13, 24–31. doi: 10.1186/1472-6890-13-24.

How to Cite

1.
Shyshkin MA. Comparative immunohistochemical study of proliferation and apoptosis in colorectal adenocarcinoma. Pathologia [Internet]. 2016Dec.23 [cited 2024Apr.20];(3). Available from: http://pat.zsmu.edu.ua/article/view/87497

Issue

Section

Original research