Apoptotic and Mitotic Index in Squamous Cell Carcinomas and Premalignant Lesions of the Uterine Cervix

Abstract

The aim of this study was to determine the frequency of apoptotic and mitotic cells in different grades of premalignant lesions and in different stages of squamous cell carcinoma (SCC) of the uterine cervix. The apoptotic and mitotic indices (A! and MI) of 55 H&E-stained sections of cervical intraepithelial neoplasia (CIN) and 30 SCCs were evaluated in light microscopy by a morphometric method. Twenty, 16, and 19 of 55 CIN cases were classified in CIN I, CIN II, and CIN III group, respectively. No apoptosis was observed in the normal epithelium next to the dysplastic mucosa. There was no statistically significant difference between CIN I and CIN II as well as CIN II and CIN III groups in terms of apoptotic and mitotic cell counts. Mitotic cell counts were found significantly higher in CIN III group when compared with CIN I and CIN II groups together. There was no statistically significant difference in the apoptotic and mitotic cell counts between nonkeratinizing and keratinizing types of SCC. In the SCC group, apoptotic cell counts did not show significant difference between tumor stages. But mitotic counts were significantly higher in advanced stage tumors. The SCC group showed significantly higher mitotic and apoptotic cell counts when compared with preneoplastic lesions. This study suggests that apoptotic function is not altered during progressive stages of dysplastic change in cervical epithelium, while proliferation is triggered only in late stages of dysplasia. Both apoptosis and mitosis are markedly increased in progression to malignancy in cervix epithelium. Mitotic cell counts may be helpful in predicting the extent of the disease in SCC. Resistance of cell death by apoptosis after invasion may accelerate the net growth of the tumor resulting in advanced disease.

Keywords

cervical intraepithelial neoplasia cervical carcinoma apoptosis mitosis

Get full access to this article

View all access options for this article.

References

1. Kerr JFR , Winterford CM , Harman BV . Apoptosis. Its significance in cancer and cancer therapy. Cancer 73:13-20, 1994

2. Majno J , Joris I . Apoptosis, oncosis, necrosis. An overview of cell death. Am J Pathol 146:3-16, 1995

3. Hockenbery D . Defining apoptosis. Am J Pathol 146: 16-19, 1995

4. Aihara M , Truong LD , Dunn JK , Wheeler TM , Scardino PT , Thompson TC . Frequency of apoptotic bodies positively correlates with Gleason grade in prostate cancer. Hum Pathol 25:797-797, 1994

5. Sinicrope FA , Ruan SB , Cleary KR . bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res 55:237-241, 1995

6. Isacson C , Kessis TD , Hedric L , Cho KR . Both cell proliferation and apoptosis increase with lesion grade in cervical neoplasia but not correlate with human papilloma virus type. Cancer Res 56:669-674, 1996

7. Kobavashi I , Matsuo K , Ishibashi Y , Kanda S , Sakai H . The proliferative activity in dysplasia and carcinoma in situ of the uterine cervix analyzed by proliferating cell nuclear antigen immunostaining and silver-binding argyrophilic nucleolar organizer region staining. Hum Pathol 25:198-198, 1994

8. Leoncini L , Del Vecchio MT , Megha T , Barbini P . Correlations between apoptotic and proliferative indices in malignant non Hodgkin's lymphomas. Am J Pathol 142:755-755, 1993

9. Kargi HA , Aktas S , Sagol O , Ermete S , Akpinar O , Akkoclu A . Apoptosis, bcl-2 and p53 expression and their relation to tumor stage in nonsmall cell lung carcinomas (NSCLC). Cancer Lett 116:185-189, 1997

10.

10. Levine EL , Renehan A , Gossiel R , Davidson SE , Roberts SA , Chadwick C , Wilkins DP , Potten CS , Hendry JH , Hunter RD . Apoptosis, intrinsic radiosensitivity and prediction of radiotherapy response in cervical carcinoma. Radiother Oncol 37:1-9, 1995

11.

11. Spencer SJ , Cataldo NA , Jaffe RB . Apoptosis in the human female reproductive tract. Obstet Gynecol Surv 51:314-323, 1996

12.

12. Baak JPA . Mitosis counting in tumors. Hum Pathol 7:683-685, 1990

13.

13. Iwasaka T , Yokoyama M , Oh-Uchida M . Detection of human papillomavirus genome and analysis of expression of c-myc and Ha-ras oncogenes in invasive cervical cancers. Gynecol Oncol 46:198-198, 1992

14.

14. Wright TC , Ferenczy A , Kurman RJ . Carcinoma and other tumors of the cervix. In Kurman RJ (ed). Blaustein's pathology of the female genital tract, Springer Verlag, New York, pp. 292-293, 1994

15.

15. Wright TC , Ferenczy A , Kurman RJ . Carcinoma and other tumors of the cervix. In Kurman RJ (ed). Blaustein's pathology of the female genital tract, Springer Verlag, New York, pp. 281-281, 1994

16.

16. Wright TC , Ferenczy A , Kurman RJ . Precancerous lesions of the cervix. In Kurman RJ (ed). Blaustein's pathology of the female genital tract, Springer Verlag, New York, pp. 246-253, 1994

17.

17. Sheets EE , Crum CP , Yeh J . Association between cervical neoplasia and apoptosis as detected by in situ nuclear labeling. Gynecol Oncol 63:94-100, 1994

18.

18. Shoji Y , Saegusa M , Takano Y , Ohbu M , Okayasu I . Correlation of apoptosis with tumor cell differentiation, progression, and HPV infection in cervical carcinoma. J Clin Pathol 49:134-138, 1996

19.

19. Sagae S , Kudo R , Kuzumaki N , Hisada T , Mugikura Y , Nihei T , Takeda T , Hashimoto M . Ras oncogene expression and progression in intraepithelial neoplasia of the uterine cervix. Cancer 66:295-295, 1990

20.

20. Tanaka T . Proliferative activity in dysplasia, carcinoma in situ and microinvasive carcinoma of the uterine cervix. Pathol Res Pract 181:531-539, 1986

21.

21. Claas ECJ , Quint WGV , Pieters WJLM , Burger MPM , Oosterhuis WJW , Lindeman J . Human papilloma virus and the three group metaphase figure as markers of an increased risk for the development of cervical carcinoma. Am J Pathol 140:497-497, 1992

22.

22. Yasuda M , Umemura S , Osamura RY , Kenjo T , Tsutsumi Y . Apoptotic cells in the human endometrium and placental villi: Pitfalls in applying the TUNNEL method. Arch Histol Cytol 58:185-190, 1995

23.

23. Kraupp BG , Ruttkay-Nedecky B , Koudelka H , Bukowska K , Bursch W , Hermann RS . In situ detection of fragmented DNA (TUNNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: A cautionary note. Hepatology 21:1465-1468, 1995

24.

24. Harrison DJ . Counting apoptosis-why and how? J Clin Pathol 49:245-246, 1996