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Changes of Ki-67 index in squamous cell carcinoma of the cervix during the early course of radiotherapy and prediction of prognosis
1Department of Radiation Oncology, Ege University School of Medicine, Turkey
2Department of Pathology, Dokuz Eyliil University School of Medicine, Turkey
3Department of Pathology, Tepecik S. S. K. Maternity Hospital, Turkey
4Department of Gynecologic Oncology, Tepecik S. S. K. Maternity Hospital, Turkey
5Department of Gynecologic Oncology, Ege University· School of Medicine, Iznir, Turkey
*Corresponding Author(s): D. Yalman E-mail:
Purpose: To determine whether changes in the Ki-67 index during the early course of radiotherapy could predict the prognosis in squamous cell carcinoma of the uterine cervix and be of value in clinical practice.
Materials and methods: Biopsy specimens from 23 cases of histologically confirmed squamous cell carcinoma of the cervix were stained with anti-Ki-67 monoclonal antibody prior to radiotherapy and after 9 Gy. The correlation between the Ki-67 index, local control and distant metastasis was determined by Spearman's correlation test.
Results: Median age of the patients was 49. According to the FIGO staging system four patients had Stage IIA, 16 had Stage IIB, one had Stage IIIA and two had Stage IIIB disease. Among the whole group brachytherapy was applied to 17 patients (17/23) and weekly cisplatin (40 mg/m2) was applied to 15 patients (15/23). The mean Ki-67 index prior to radiotherapy and after 9 Gy for the entire group were 58.5% and 46.0%, respectively. The Ki-67 index after 9 Gy decreased in most of the patients (74%). During a median follow-up of 23 months four patients developed local recurrence and four patients developed distant metastasis. No significant correlation was detected among the local control and changes in Ki-67 index after 9 Gy, whereas there was a moderate correlation between distant metastasis and changes in Ki-67 index after 9 Gy (r = 0.51, p = 0.01).
Conclusion: The Ki-67 index can be used safely as a proliferation marker in cervical carcinomas, and changes in the Ki-67 index during the early course of radiotherapy may predict the metastatic potential. However prospective studies including a large number of patients with long-term follow-up are necessary to confirm the clinical utility of this marker in cervical cancer.
Carcinoma of the cervix; Radiotherapy; Ki-67 index
S. A. Kamer,D. Yalman,E. Ozer,S. Sayhan,M. Hanhan,A. Ozsaran,A. Haydaroglu. Changes of Ki-67 index in squamous cell carcinoma of the cervix during the early course of radiotherapy and prediction of prognosis. European Journal of Gynaecological Oncology. 2003. 24(3-4);287-292.
[1] Eifel P.J., Berek J.S., Thigpen J.T.: "Cancer of the cervix, vagina and vulva". In: De Vita V., Hellman S., Rosenberg S.A. (eds.). Cancer, Principles and Practice of Oncology, Philadelphia, New York: Lippincott-Raven Publishers, 1997, 1433.
[2] Takeshi K., Katsuyuki K., Yoshiaki T., Teppei S., Tadayoshi M., Akira M. et al.: "Definitive radiotherapy combined with highdose-rate brachytherapy for stage III carcinoma of the uterine cervix: Retrospective analysis of prognostic factors concerning patient characteristics and treatment parameters". Int. J. Radiat. Oneal. Biol. P hys., 1998, 41 (2), 319.
[3] Ming-Tak Ho D., Hsu C. Y., Chiang H.: "MIB-1 labeling index as a prognostic indicator for survival in patients with FIGO stage IB squamous cell carcinoma of the cervix". Gynecol. Oneal., 2000, 76, 97.
[4] Perez C. A.: "Uterine cervix". In: Perez C. A., Brady L. W. (eds.). Principles and Practice of Radiation Oncology, Philadelphia, New York: J.B. Lipincott Company, 1998, 1733.
[5] Dervan P. A., Magee H. M., Buckley C., Carney D. N.: "Proliferating cell nuclear antigen counts in formalin-fixed paraffinembedded tissue correlate with Ki-67 in fresh tissue". Am. J. Clin. Pathol., 1992, 97 (5), 21.
[6] Gerdes J., Lemke H., Baisch H., Wacker H., 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, /33 (4), 1710.
[7] Nakano T., Oka K.: "Transition of Ki-67 index of uterine cervical tumors during radiation therapy". Cancer, 1991, 68, 517.
[8] Valente G., Orecchia R., Gandolfo S., Arnaudo M., Ragona R., Kerim S. et al.: "Can Ki-67 immunostaining predict response to radiotherapy in oral squamous cell carcinoma?". J. Clin. Pathol., 1994, 47, 109.
[9] Costa A., Salvatori P., Molinari R., Motta R., Cerutti A., Silverstrini R.: "Cell kinetics to monitor radioresponsivity in human epidermoid carcinoma". Basic App. Histochem., 1986, 30, 206.
[10] Felix Wong W. S., McGuire L. J.: "Tumor growth fraction in cervical carcinoma". Gynecol. Oneal., 1991, 40, 48.
[11] Felix Wong W. S.: "Immunhistochemical detection of proliferating tumor cells in cervical cancer using monoclonal antibody Ki-67". Gynecol. Obstet. Invest., 1994, 37, 123.
[12] Oka K., Nakano T., Hoshi T.: "Transient increases of growth fraction during fractionated radiation therapy for cervical carcinoma". Cancer, 1993, 72 (9), 2621.
[13] Avall-Lundqvist E. H., Silfversward C., Aspenblad U., Nilsson B R., Auer G. U.: "The impact of tumour angiogenesis, p53 overexpression and proliferative activity (MIB-1) on survival in squamous cervical carcinoma". Eur. J. Cancer, 1997, 33 (11), 1799.
[14] Kovarik J., Skry G. D., Mikel J., Svoboda V. H.J.: "Changes of Ki-67 index of various tumors during radiation therapy". Neoplasma, 1996, 43 (2), 89.
[15] Bar J. K., Harzolinska A., Markoowska J., Nowak M.: "Studies on tumor proliferation using monoclonal antibody, Ki-67 and expression of p53 in cancer of the uterine cervix". Eu,: J. Gynecol Oncol.,1 996,17, 378.
[16] Brown D. C., Cole D., Gatter K. C., Mason D. Y.: "Carcinoma of the cervix uteri: an assessment of tumour proliferation using the monoclonal antibody Ki-67". Bl: J. Cancer, 1988, 57 (2), 178.
[17] Cole D. J., Brown D. C., Crossley E., Alcock C. J., Gatter K. C.: "Carcinoma of the cervix uteri: an assessment of the relationship of tumour proliferation to prognosis". Br. J. Cancer,1 992,6 5 (5), 783.
[18] Nakano T., Oka K.: "Differential values of Ki-67 index and mitollc index of proliferating cell population". Cancer, 1993, 15, 72 (8), 2401.
[19] Garzetti G., Ciavattini A., Lucarini G., Goteri G., De Nictolis M., Muzzioli M. et al.: "MIB-1 immunstaining in Stage I squamous cervical carcinoma. Relationship with natural killer activity" Gynecol. Oneal., 1995, 58, 28.
[20] Nakano T., Oka K., Ishikawa A., Morita S.: "Immunhistochemi- cal prediction of radiation response and local control in radiation therapy for cervical cancer". Cancer Detect. Prev., 1998, 22 (2), 120.
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