Annals of Surgical Oncology

, Volume 22, Issue 9, pp 2978–2987 | Cite as

Tumor Mitotic Rate Added to the Equation: Melanoma Prognostic Factors Changed?

A Single-Institution Database Study on the Prognostic Value of Tumor Mitotic Rate for Sentinel Lymph Node Status and Survival of Cutaneous Melanoma Patients
  • M. J. Speijers
  • E. Bastiaannet
  • S. Sloot
  • A. J. H. Suurmeijer
  • H. J. Hoekstra
Melanomas

Abstract

Background

This study aimed to investigate the predictive value of the tumor mitotic rate per mm2 (TMR) for sentinel lymph node (SLN) status and survival in intermediate and thick cutaneous melanoma.

Methods

Patients treated for stage I and II melanoma with wide local excision and SLN biopsy between May 1995 and May 2013 were analyzed. In case of insufficient data regarding TMR, pathology slides were reanalyzed. Prognostic factors for SLN status and survival were analyzed with the emphasis on TMR, which was analyzed as a continuous variable, dichotomized (median value) and categorized by two methods.

Results

The study analyzed 453 patients with complete TMR data. The median Breslow thickness was 2.20 mm, and 31.8 % of patients had tumor-positive sentinel lymph node biopsies (SLNBs). In the univariate analysis, TMR was associated with tumor-positive SLNB. This association was not significant in the multivariate analysis. Breslow thickness, primary tumor location on trunk and legs, and younger age were associated with tumor-positive SNLB. At a median follow-up of 47 months, 119 patients (26.3 %) had recurrent disease, and 92 (20.3 %) had died of melanoma. In the univariate analysis, TMR could be established as a significant prognostic factor for disease-free and disease-specific survival, but not in the multivariate analyses. Breslow thickness, ulcerated melanoma, and tumor-positive SLNB were significant prognostic factors for survival.

Conclusion

The study was unable to establish TMR as an independent prognostic factor associated with the presence of SLN metastasis. Regarding survival, increasing TMR showed a strong association with decreased survival in the univariate analysis, but this association was rendered nonsignificant by the importance of Breslow thickness and ulceration status in the multivariate model.

Keywords

Melanoma Sentinel Lymph Node Biopsy Breslow Thickness Completion Lymph Node Dissection Sentinel Lymph Node Status 

Notes

Acknowledgment

The project was partially supported by the Melanoma Sarcoma Groningana Foundation, Groningen, The Netherlands.

Disclosures

There are no conflicts of interest.

References

  1. 1.
    Balch CM, Greshenwald JE, Soong SJ, et al. Final version of the 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199–206.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Thompson JF, Soong SJ, Balch CM, et al. Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J Clin Oncol. 2011;29:2199–205.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Sondak VK, Taylor JMG, Sabel MS, et al. Mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model. Ann Surg Oncol. 2004;11:247–58.PubMedCrossRefGoogle Scholar
  4. 4.
    Paek SC, Griffith KA, Johnson TM, et al. The impact of factors beyond Breslow depth on predicting sentinel lymph node positivity in melanoma. Cancer. 2006;109:100–8.CrossRefGoogle Scholar
  5. 5.
    Roach BA, Burton AL, Mays MP, et al. Does mitotic rate predict sentinel lymph node metastasis or survival in patients with intermediate and thick melanoma? Am J Surg. 2010;200:759–64.PubMedCrossRefGoogle Scholar
  6. 6.
    De Vries M, Speijers MJ, Bastiaannet E, et al. Long-term follow-up reveals that ulceration and sentinel lymph node status are the strongest predictors for survival in patients with primary cutaneous melanoma. Eur J Surg Oncol. 2011;37:681–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Doting MH, Hoekstra HJ, Plukker JT, et al. Is sentinel node biopsy beneficial in melanoma patients? A report on 200 patients with cutaneous melanoma. Eur J Surg Oncol. 2002;28:673–8.PubMedCrossRefGoogle Scholar
  8. 8.
    McGovern VJ, Cochran AJ, Van der Esch EP et al. The classification of malignant melanoma, its histological reporting, and registration: a revision of the 1972 Sydney classification. Pathology. 1986;18:12–21.PubMedCrossRefGoogle Scholar
  9. 9.
    Francken AB, Shaw HM, Thompson JF, et al. The prognostic importance of tumor mitotic rate confirmed in 1,317 patients with primary cutaneous melanoma and long follow-up. Ann Surg Oncol. 2004;11:426–33.PubMedCrossRefGoogle Scholar
  10. 10.
    Azzola MF, Shaw HM, Thompson JF, et al. Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3,661 patients from a single center. Cancer. 2003;97:1488–98.PubMedCrossRefGoogle Scholar
  11. 11.
    Van Akkooi ACJ, de Wilt JHw, Verhoef C, et al. High positive sentinel identification rate by EORTC Melanoma Group Protocol: prognostic indicators of metastatic patterns after sentinel node biopsy in melanoma. Eur J Cancer. 2006;42:372–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Gershenwald JE, Thompson W, Mansfield PF, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol. 1999;17:976–83.PubMedGoogle Scholar
  13. 13.
    White RL, Ayers GD, Stell VH, et al. Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database. Ann Surg Oncol. 2011;18: 3593–600.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Kruper LL, Spitz FR, Czerniekcki BJ, et al. Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma. Cancer. 2006;107:2436–45.PubMedCrossRefGoogle Scholar
  15. 15.
    Mocellin S, Ambrosi A, Montesco MC, et al. Support vector machine learning model for the prediction of sentinel node status in patients with cutaneous melanoma. Ann Surg Oncol. 2006;13:1113–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Mitra A, Conway C, Walker C, et al. Melanoma sentinel node biopsy and prediction models for relapse and overall survival. Br J Cancer. 2010;103:1229–36.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Fairbairn NG, Orfaniotis G, Butterworth M. Sentinel lymph node biopsy in thick malignant melanoma: a 10-year single-unit experience. J Plast Reconstr Aesthet Surg. 2012;65:1396–402.PubMedCrossRefGoogle Scholar
  18. 18.
    Karakousis GC, Gimotty PA, Botbyl JD, et al. Predictors of regional nodal disease in patients with thin melanomas. Ann Surg Oncol. 2006;13:533–41.PubMedCrossRefGoogle Scholar
  19. 19.
    Attis MG, Vollmer RT. Mitotic rate in melanoma: a reexamination. Am J Clin Pathol. 2007;127:380–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Ostmeier H, Fuchs B, Otto F, et al. Can immunohistochemical markers and mitotic rate improve prognostic precision in patients with primary melanoma? Cancer. 1999;85:2391–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Schmid-Wendtner MH, Baumert J, Schmidt M, et al. Prognostic index for cutaneous melanoma: an analysis after follow-up of 2,715 patients. Melanoma Res. 2001;11:619–26.PubMedCrossRefGoogle Scholar
  22. 22.
    Balch CM, Soong SJ, Gershenwald JE, Thompson JF, Coit DG, Atkins MB, et al. Age as a prognostic factor in patients with localized melanoma and regional metastases. Ann Surg Oncol. 2013;20:3961–8.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Stucky CCH, Gray RJ, Dueck AC, et al. Risk factors associated with local in-transit recurrence of cutaneous melanoma. Am J Surg. 2010;200:770–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Scolyer RA, Shaw HM, Thompson JF, et al. Interobserver reproducibility of histopathologic prognostic variables in primary melanoma. Am J Surg Pathol. 2003;27:1571–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Balch CM, Gerschenwald JE, Soong SJ, Thompson JF, Ding S, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: compariscon of nodal micrometastases versus macrometastases. J Clin Oncol. 2010;28:2452–9.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • M. J. Speijers
    • 1
  • E. Bastiaannet
    • 1
  • S. Sloot
    • 1
  • A. J. H. Suurmeijer
    • 2
  • H. J. Hoekstra
    • 1
  1. 1.Division of Surgical Oncology, University Medical Centre GroningenUniversity of GroningenGroningenThe Netherlands
  2. 2.Department of Pathology, University Medical Centre GroningenUniversity of GroningenGroningenThe Netherlands

Personalised recommendations