Display options
Cite
Cao CD, Rico-Castillo J, De Cotiis D, et al. Digital Quantification of Ki-67 and PHH3 in the Classification of Uterine Smooth Muscle Tumors. Int J Gynecol Pathol. 2021;40(6):549-555doi: 10.1097/PGP.0000000000000739.
Cao, C. D., Rico-Castillo, J., De Cotiis, D., Richard, S. D., Rosenblum, N. G., & Chan, J. S. Y. (2021). Digital Quantification of Ki-67 and PHH3 in the Classification of Uterine Smooth Muscle Tumors. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists, 40(6), 549-555. https://doi.org/10.1097/PGP.0000000000000739
Cao, Connie D, et al. "Digital Quantification of Ki-67 and PHH3 in the Classification of Uterine Smooth Muscle Tumors." International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists vol. 40,6 (2021): 549-555. doi: https://doi.org/10.1097/PGP.0000000000000739
Cao CD, Rico-Castillo J, De Cotiis D, Richard SD, Rosenblum NG, Chan JSY. Digital Quantification of Ki-67 and PHH3 in the Classification of Uterine Smooth Muscle Tumors. Int J Gynecol Pathol. 2021 Nov 01;40(6):549-555. doi: 10.1097/PGP.0000000000000739. PMID: 33323861.
Copy Download .nbib Format: NLM
Share it on

Int J Gynecol Pathol. 2021 Nov 01;40(6):549-555. doi: 10.1097/PGP.0000000000000739.

Digital Quantification of Ki-67 and PHH3 in the Classification of Uterine Smooth Muscle Tumors.

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists

Connie D Cao, Jesus Rico-Castillo, Dan De Cotiis, Scott D Richard, Norman G Rosenblum, Joanna S Y Chan

PMID: 33323861 DOI: 10.1097/PGP.0000000000000739

Abstract

Uterine smooth muscle tumors are the most common tumors of the female genital tract and include leiomyoma (LM) and its variants, smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). Accurate diagnosis of LMS is determined by nuclear atypia, mitotic count, and the presence or absence of tumor cell necrosis, a process which is often difficult and subjective. In this study, we correlated digital quantification of proliferation marker Ki-67 and mitotic marker phosphohistone H3 (PHH3) to mitotic count, classification of uterine smooth muscle tumors, and clinical outcomes. A total of 39 cases (17 LMS, 5 STUMP, 10 LM with bizarre nuclei, and 7 LM) were included. Mitotic count, Ki-67, and PHH3 were significantly correlated. When comparing the LMS group to the STUMP, LM with bizarre nuclei, and LM groups combined, LMS showed a significantly greater digital quantification of Ki-67 (median 10.6% vs. 0.4%, P<0.001) and PHH3 (median 0.5% vs. 0.14%, P=0.022). Ki-67 was a better predictor of LMS compared with PHH3 (area under the curve 0.92 vs. 0.73, P=0.017). Above a threshold Ki-67 value of 3.8%, the sensitivity was 82% and specificity was 91%. Clinical outcomes were available for 10 patients (8 LMS and 2 STUMP), and inferior progression-free survival was noted for patients with higher Ki-67 values. Overall, this study suggests that digital quantification of Ki-67 can potentially aid in diagnosis of LMS.

Copyright © 2020 by the International Society of Gynecological Pathologists.

Conflict of interest statement

The authors declare no conflict of interest.

References

  1. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol 1990;94:435–8. - PubMed
  2. Kapp DS, Shin JY, Chan JK. Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas: emphasis on impact of lymphadenectomy and oophorectomy. Cancer 2008;112:820–30. - PubMed
  3. Kurman RJ, Carcangiu ML, Herrington CS, et al. WHO Classification of Tumours, 4th ed. Lyon, France: IARC Press; 2014. - PubMed
  4. Bell SW, Kempson RL, Hendrickson MR. Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Surg Pathol 1994;18:535–58. - PubMed
  5. Tapia C, Kutzner H, Mentzel T, et al. Two mitosis-specific antibodies, MPM-2 and phospho-histone H3 (Ser28), allow rapid and precise determination of mitotic activity. Am J Surg Pathol 2006;30:83–9. - PubMed
  6. Veras E, Malpica A, Deavers MT, et al. Mitosis-specific marker phospho-histone H3 in the assessment of mitotic index in uterine smooth muscle tumors: a pilot study. Int J Gynecol Pathol 2009;28:316–21. - PubMed
  7. Chen L, Yang B. Immunohistochemical analysis of p16, p53, and Ki-67 expression in uterine smooth muscle tumors. Int J Gynecol Pathol 2008;27:326–32. - PubMed
  8. Chow KL, Tse KY, Cheung CL, et al. The mitosis-specific marker phosphohistone-H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome-based study. Histopathology 2017;70:746–55. - PubMed
  9. D’Angelo E, Espinosa I, Ali R, et al. Uterine leiomyosarcomas: tumor size, mitotic index, and biomarkers Ki67, and Bcl-2 identify two groups with different prognosis. Gynecol Oncol 2011;121:328–33. - PubMed
  10. Mayerhofer K, Lozanov P, Bodner K, et al. Ki-67 expression in patients with uterine leiomyomas, uterine smooth muscle tumors of uncertain malignant potential (STUMP) and uterine leiomyosarcomas (LMS). Acta Obstet Gynecol Scand 2004;83:1085–8. - PubMed
  11. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837–45. - PubMed
  12. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993;39:561–77. - PubMed
  13. Pang SJ, Li CC, Shen Y, et al. Value of counting positive PHH3 cells in the diagnosis of uterine smooth muscle tumors. Int J Clin Exp Pathol 2015;8:4418–26. - PubMed
  14. Zivanovic O, Jacks LM, Iasonos A, et al. A nomogram to predict postresection 5-year overall survival for patients with uterine leiomyosarcoma. Cancer 2012;118:660–9. - PubMed
  15. Taylor WR. FACS-based detection of phosphorylated histone H3 for the quantitation of mitotic cells. Methods Mol Biol 2004;281:293–9. - PubMed
  16. O’Neill CJ, McBride HA, Connolly LE, et al. Uterine leiomyosarcomas are characterized by high p16, p53 and MIB1 expression in comparison with usual leiomyomas, leiomyoma variants and smooth muscle tumours of uncertain malignant potential. Histopathology 2007;50:851–8. - PubMed
  17. Leiser AL, Anderson SE, Nonaka D, et al. Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma. Gynecol Oncol 2006;101:86–91. - PubMed

Publication Types