Expression of Proliferating Cell Nuclear Antigen (PCNA) in breast carcinoma and its association with Ki67 and tumor grade in mastectomy specimens
Keywords:
Carcinoma breast, Histological tumor grade, Immunohistochemistry, Ki67, PCNA
Abstract
Background: Breast cancer ranks first among cancer in urban population of India, and 2nd most common in the rural population. Proliferative activity acts as an adjunct and gives prognostic importance in breast cancer. However, the best method for measurement of proliferative rate is controversial. The aim was to evaluate the association between PCNA labeling index (PCNA-LI) and Ki67 labeling index (Ki67-LI) and their correlation with histological grade.Methods: Seventy cases of simple and modified Radical Mastectomy specimens with the diagnosis of carcinoma breast were included in the study. H&E stained sections were examined for assessment of histological grade. IHC scoring was done for the markers Ki-67 and PCNA. Correlation of PCNA with Ki67 and tumor grade was performed.Result: 18 specimens were grade 1 tumors, 36 cases were grade 2 and 16 were grade 3. 90.0% of tumors were positive for PCNA index and Ki-67 positivity was observed in 85.7% cases, median and mean values of PCNA and Ki67 were 52.0, 51.64+/-37.475, and 24.50, 26.17± 24.183 respectively. Final score was divided into low and high index using median value as a cut off. Ki-67 LI showed strong positive correlation with histological grade (p=0.0001). PCNA LI showed positive correlation with histological grade (p=0.041) but no correlation was observed with Ki-67 LI (p=0.232)Conclusion: PCNA marker cannot substitute Ki67 but may be used as an additional marker to assess proliferative activity along with other markers. It may be useful to categorize subgroups with different grades of proliferative activity due to its easy applicability and assessment techniques. DOI: 10.21276/apalm.2017.1191References
1. Lyon, France: International Agency for Research on cancer. Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J cancer, 2013;132(5):1133-45.
2. Sullivan RP, Mortimer G, Muircheartaigh IO. Cell proliferation in breast tumours: analysis of histological parameters Ki67 and PCNA expression. Ir J Med Sci. 1993; 162(9):343-7.
3. Albert A. Keshgegian, Avital cnaan. Proliferation Markers in Breast Carcinoma Mitotic Figure Count, S-Phase Fraction, Proliferating Cell Nuclear Antigen, Ki-67 and MIB-1. Am J Clin Pathol 1995;104:42-49.
4. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984; 133(4):1710-5.
5. Simpson, JF, Gray R, Dressler LG, Cobau CD, Falkson CI, Gilchrist KW. et al. Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J Clin Oncol 2000; 18: 2059-69
6. Van Diest, Paul J, Brugal, Gerard, Baak, Jan PA. Proliferation markers in tumours: interpretation and clinical value J Clin Pathol 1998; 51(10): 716-724.
7. Schönborn I, Minguillon.C, Möhner.M, Ebeling . PCNA as a potential prognostic marker in breast cancer, breast Volume 3, Issue 2, June 1994, Pages 97-102
8. Noguchi, Thomas MM, Kitagawa H, Kinoshita K, et al. The prognostic significance of proliferating cell nuclear antigen in breast cancer: correlation with DNA ploidy, c-erbB-2 expression, histopathology, lymph node metastases and patient survival. Int. J. Oncol. 2: 985-989. 1993
9. Pelosi G, Bresaola E, Rodella S, Manfrin E, Piubello Q, Schiavon I, Iannucci A. Expression of proliferating cell nuclear antigen, Ki-67 antigen, estrogen receptor protein, and tumor suppressor p53 gene in cytologic samples of breast cancer: an immunochemical study with clinical, pathobiological, and histologic correlations. Diagn Cytopathol. 1994;11(2):131-40
10. Brown DC, Gatter KC. Monoclonal antibody Ki67: its use in histopathology. Histopathology 1990;17:489-503.
11. Caly M, Genin P, Ghuzlan AA. Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma. Methodological aspects and prognostic value in a series of 257 cases. Anticancer Res 2004; 24: 3283-88.
12. Leonardi E, Girlando S, Serio G. PCNA and Ki-67 expression in breast carcinoma; Correlation with clinical biological variables. J Clin Patrhol 1992; 45: 416-419.
13. Hall PA, Levison DA, Woods AL, et al. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of
deregulated expression in some neoplasms. J Pathol 1990;162:285-94.
14. Thomas M, Noguchi M, Kitagawa H, Kinoshita K, Miyazaki I Poor prognostic value of proliferating cell nuclear antigen labeling index in breast carcinoma. J Clin Pathol 1993; 46: 525-528
15. Surowiak P, Pudelko M, Maciejczyk A. The relationship of the expression of proliferetron--related antigens Ki67 and PCNA in the cells of ductal breast cancer with the differentiation grade. Ginekol Pol 2005; 76: 9-14.
16. Dawson AE, Norton JA, Weinberg DS. Comparative assessment of proliferation and DNA content in breast carcinoma by image analysis and flow cytometry. Am J Pathol 1990;136:1 115-24.
17. Battersby S, Anderson TJ. Correlation of proliferative activity in breast tissue using PCNA/cyclin. Hum Pathol 1990;21:781.
18. Mercer EW, Shield MT, Amin M, et al. Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. Proc Natl Acad Sci USA 1990;87:6166-70.
19. Haneda H, Katabami M, Miyamoto H, et al. The relationship of the proliferating cell nuclear antigen protein to CDDP resistance of a murine leukemia cell line P388/CDDP. Oncology 1991;48:234-8.
2. Sullivan RP, Mortimer G, Muircheartaigh IO. Cell proliferation in breast tumours: analysis of histological parameters Ki67 and PCNA expression. Ir J Med Sci. 1993; 162(9):343-7.
3. Albert A. Keshgegian, Avital cnaan. Proliferation Markers in Breast Carcinoma Mitotic Figure Count, S-Phase Fraction, Proliferating Cell Nuclear Antigen, Ki-67 and MIB-1. Am J Clin Pathol 1995;104:42-49.
4. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984; 133(4):1710-5.
5. Simpson, JF, Gray R, Dressler LG, Cobau CD, Falkson CI, Gilchrist KW. et al. Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J Clin Oncol 2000; 18: 2059-69
6. Van Diest, Paul J, Brugal, Gerard, Baak, Jan PA. Proliferation markers in tumours: interpretation and clinical value J Clin Pathol 1998; 51(10): 716-724.
7. Schönborn I, Minguillon.C, Möhner.M, Ebeling . PCNA as a potential prognostic marker in breast cancer, breast Volume 3, Issue 2, June 1994, Pages 97-102
8. Noguchi, Thomas MM, Kitagawa H, Kinoshita K, et al. The prognostic significance of proliferating cell nuclear antigen in breast cancer: correlation with DNA ploidy, c-erbB-2 expression, histopathology, lymph node metastases and patient survival. Int. J. Oncol. 2: 985-989. 1993
9. Pelosi G, Bresaola E, Rodella S, Manfrin E, Piubello Q, Schiavon I, Iannucci A. Expression of proliferating cell nuclear antigen, Ki-67 antigen, estrogen receptor protein, and tumor suppressor p53 gene in cytologic samples of breast cancer: an immunochemical study with clinical, pathobiological, and histologic correlations. Diagn Cytopathol. 1994;11(2):131-40
10. Brown DC, Gatter KC. Monoclonal antibody Ki67: its use in histopathology. Histopathology 1990;17:489-503.
11. Caly M, Genin P, Ghuzlan AA. Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma. Methodological aspects and prognostic value in a series of 257 cases. Anticancer Res 2004; 24: 3283-88.
12. Leonardi E, Girlando S, Serio G. PCNA and Ki-67 expression in breast carcinoma; Correlation with clinical biological variables. J Clin Patrhol 1992; 45: 416-419.
13. Hall PA, Levison DA, Woods AL, et al. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of
deregulated expression in some neoplasms. J Pathol 1990;162:285-94.
14. Thomas M, Noguchi M, Kitagawa H, Kinoshita K, Miyazaki I Poor prognostic value of proliferating cell nuclear antigen labeling index in breast carcinoma. J Clin Pathol 1993; 46: 525-528
15. Surowiak P, Pudelko M, Maciejczyk A. The relationship of the expression of proliferetron--related antigens Ki67 and PCNA in the cells of ductal breast cancer with the differentiation grade. Ginekol Pol 2005; 76: 9-14.
16. Dawson AE, Norton JA, Weinberg DS. Comparative assessment of proliferation and DNA content in breast carcinoma by image analysis and flow cytometry. Am J Pathol 1990;136:1 115-24.
17. Battersby S, Anderson TJ. Correlation of proliferative activity in breast tissue using PCNA/cyclin. Hum Pathol 1990;21:781.
18. Mercer EW, Shield MT, Amin M, et al. Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. Proc Natl Acad Sci USA 1990;87:6166-70.
19. Haneda H, Katabami M, Miyamoto H, et al. The relationship of the proliferating cell nuclear antigen protein to CDDP resistance of a murine leukemia cell line P388/CDDP. Oncology 1991;48:234-8.
Published
2017-02-19
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