RELATIONSHIP BETWEEN ARGYROPHILIC PROTEINS OF NUCLEOLAR ORGANIZER REGIONS AND ANTIGEN KI-67 WITH CLINICAL AND MORPHOLOGICAL PARAMETERS AND SURVIVAL IN LUNG ADENOCARCINOMA
Abstract
Argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR proteins) and Ki-67 antigen were investigated in patients with lung adenocarcinoma. Tumors with low and high content of Ag-NOR proteins and proliferation index (PI) Ki-67 were determined. The relationship between the Ag-NOR content and T and N parameters, tumor size of 3 cm or more and stage of the disease was found. High survival rates in patients with lung adenocarcinoma were associated with the low content of Ag-NOR proteins and PI Ki-67 and low survival rates were related to the high content of Ag-NOR proteins and PI Ki-67. The intermediate survival rates were related to the opposite values of the content of Ag-NOR proteins and PI Ki-67. The tumor size, N parameter and the content of Ag-NOR proteins had an independent effect on survival of patients. Survival was related to the size of the tumor in lung cancer patients having no lymph node involvement and it was related to the content of Ag-NOR proteins in cases with the presence of metastases. Mutual study of Ag-NOR proteins and antigen Ki-67 has differential diagnostic and prognostic value in lung adenocarcinoma.
About the Authors
D. S. Kobyakov
City Hospital, Kogalym
Russian Federation
Russian Federation
V. V. Klimachev
Altai Medical University, Barnaul
Russian Federation
Russian Federation
A. M. Avdalyan
Altai branch of N.N. Blokhin Russian Cancer Research Center, Barnaul
Russian Federation
Russian Federation
I. P. Bobrov
Altai branch of N.N. Blokhin Russian Cancer Research Center, Barnaul
Russian Federation
Russian Federation
A. F. Lazarev
Altai branch of N.N. Blokhin Russian Cancer Research Center, Barnaul
Russian Federation
Russian Federation
References
1. Кобяков Д.С. Сравнительный анализ пролиферативной активности эпителиальных клеток аденомы и рака толстой кишки: Автореф. дис. ... канд. мед. наук. Томск, 2006.
2. Пономарева А.А., Рыкова Е.Ю., Чердынцева Н.В. и др. Сравнительный анализ эпигенетических и белковых маркеров в крови больных немелкоклеточным раком легкого // Сибирский онкологический журнал. 2011. № 5 (47). С. 40–45.
3. Райхлин Н.Т., Букаева И.А., Смирнова Е.А. и др. Значение экспрессии ядрышковых аргирофильных белков и антигена Ki-67 в определении пролиферативной активности клеток и прогноза «малого» (Т1) рака легкого // Архив патологии. 2008. Т. 70 (3). С. 15–18.
4. Шацева Т.А, Мухина М.С. Антиген Ki-67 в оценке опухолевой пролиферации. Его структура и функция // Вопросы онкологии. 2004. Т. 50 (2). С. 157–164.
5. Aubele M., Biesterfeld S., Derenzini M. et al. Guidelines of AgNOR quantization // Zentralbl. Pathol. 1994. Vol. 140 (1). P. 107–108.
6. Brown D.C., Gatter K.C. Ki67 protein: the immaculate deception? // Histopathology. 2002. Vol. 40 (1). P. 2–11.
7. Canet V., Montmasson M.P., Usson Y. et al. Correlation between silver-stained nucleolar organizer region area and cell cycle time // Cytometry. 2001. Vol. 43 (2). P. 110–116.
8. Carvalho P.E., Antonangelo L., Bernardi F.D. et al. Useful prognostic panel markers to express the biological tumor status in resected lung adenocarcinomas // Jpn. J. Clin. Oncol. 2000. Vol. 30 (11). P. 478–486.
9. Ceccarelli C., Trere D., Santini D. et al. AgNORs in breast tumours // Micron. 2000. Vol. 31 (2). P. 143–149.
10. Derenzini M., Sirri V., Trere D., Ochs R. The quantity of nucleolar proteins nucleolin and protein B23 is related to cell doubling time in human cancer cells // Lab. Invest. 1995. Vol. 73 (4). P. 497–502.
11. Derenzini M., Trere D. Standardization of interphase Ag-NOR measurement by means of an automated image analysis system using lymphocytes as an internal control // J. Pathol. 1991. Vol. 165 (4). P. 337–342.
12. Giuffre G., Mormandi F., Barresi V. et al. Quantity of AgNORs in gastric endocrine carcinoid tumours as a potential prognostic tool // Eur. J. Histochem. 2006. Vol. 50 (1). P. 45–50.
13. Jakobsen J.N., Sorensen J.B. Clinical impact of Ki-67 labeling index in non-small cell lung cancer // Lung Cancer. 2013. Vol. 79 (1). P. 1–7.
14. Kaneko S., Ishida T., Sugio K. et al. Nucleolar organizer regions as a prognostic indicator for stage I non-small cell lung cancer // Cancer Res. 1991. Vol. 51 (15). P. 4008–4011.
15. Lorenzato M., Abboud P., Lechki C. et al. Proliferation assessment in breast cancer: a double-staining technique for AgNOR quantification in MIB-1 positive cells especially adapted for image cytometry // Micron.2000. Vol. 31 (2). P. 151–159.
16. Matheus R.S., Bernardi F., Del C. et al. Nuclear markers (star volume, mitotic index, AgNOR and Ki-67) of the primary tumor and its metastasis in non-small cell lung carcinomas // Pathol. Res. Pract. 2004. Vol. 200 (1). P. 13–23.
17. Ofner D., Hittmair A., Marth C. et al. Relationship between quantity of silver-stained nucleolar organizer regions associated proteins (Ag-NORs) and population doubling time in ten breast cancer cell lines // Pathol. Res. Pract. 1992. Vol. 188 (6). P. 742–746.
18. Ogura S., Abe S., Sukoh N. et al. Correlation between nucleolar organizer regions visualized by silver staining and the growth rate of lung adenocarcinoma // Cancer. 1992. Vol. 70 (1). P. 63–68.
19. Pich A., Chiusa L., Margaria E. Prognostic relevance of AgNORs in tumor pathology // Micron. 2000. Vol. 31 (2). P. 133–141.
20. Ploton D., Menager M., Jeannesson P. et al. Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer region at the optical level // Histochem J. 1986. Vol. 18 (1). P. 5–14.
21. Rodrigues O.R., Antonangelo L., Yagi N. et al. Prognostic significance of argyrophilic nucleolar organizer region (AgNOR) in resected non-small cell lung cancer (NSCLC) // Jpn. J. Clin. Oncol. 1997. Vol. 27 (5). P. 298–304.
22. Roussel P., Hernandez-Verdun D. Identification of AgNOR proteins, markers of proliferation related to ribosomal gene activity // Exp. Cell Res. 1994. Vol. 214 (2). P. 465–472.
23. Scholzen T., Gerdes J. The Ki-67 protein: from the known and the unknown // J. Cell Physiol. 2000. Vol. 182 (3). P. 311–322.
24. Sirri V., Roussel P, Hernandez-Verdun D. The AgNOR proteins: qualitative and quantitative changes during the cell cycle // Micron. 2000. Vol. 31 (2). P. 121–126.
25. Travis W.D., Brambilla E., Muller-Hermelink H.K., Harris C.C. (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. IARC Press: Lyon, 2004.
26. Trere D., Pession A., Montanaro L. et al. AgNOR protein expression and tumor growth rate of human carcinoma xenografts growing subcutaneously in nude mice // Eur. J. Histochem. 1997. Vol. 41 (suppl.2). P. 153–154.
27. van Diest P.J., Brugal G., Baak J.P. Proliferation markers in tumours: interpretation and clinical value // J. Clin. Pathol. 1998. Vol. 51 (10). P. 716–724.
Review
For citations:
Kobyakov D.S., Klimachev V.V., Avdalyan A.M., Bobrov I.P., Lazarev A.F. RELATIONSHIP BETWEEN ARGYROPHILIC PROTEINS OF NUCLEOLAR ORGANIZER REGIONS AND ANTIGEN KI-67 WITH CLINICAL AND MORPHOLOGICAL PARAMETERS AND SURVIVAL IN LUNG ADENOCARCINOMA. Siberian journal of oncology. 2013;(5):5-11. (In Russ.)
Views:
436
Email this article 
