Research highlights

Achievements - from the 1960s to the present

Melanoma Institute Australia, and its predecessor the Sydney Melanoma Unit, has been at the forefront of melanoma research for decades.

• In 1972 Dr Vincent McGovern, a pathologist from the Sydney Melanoma Unit (now Melanoma Institute Australia) together with Dr Wallace Clark from the United States, found that levels of invasion were important in determining prognosis of cutaneous melanoma.  These subsequently became known as Clark levels, but Dr McGovern made fundamentally important contributions to this concept and validated it in a major study (1). 
• Together with Dr Helen Shaw and Professor Gerry Milton, Dr McGovern published the first detailed analysis of histologic features of primary melanomas that were significant independent predictors of prognosis (2). 
• Development by Professor John Thompson of the “isolated limb infusion” technique, a less invasive alternative to isolated limb perfusion for regional chemotherapy in patients with metastatic melanoma confined to a limb.  This technique has now been adopted in other Australian melanoma centres, and in North America, Britain, Europe, and South America (3).
• Since the adoption of lymphatic mapping and sentinel lymph node biopsy for patients with cutaneous melanoma in the early 1990s, MIA researchers have undertaken studies providing new insights into cutaneous lymphatic anatomy, including some clinically relevant and unexpected new drainage pathways (4).
• Development of one of the largest melanoma research databases in the world; the last two versions of the American Joint Committee on Cancer’s Melanoma Staging Manual have been heavily dependent on data from this database (5).
• In 2003, Institute researchers reported that tumour mitotic rate is an independent predictor of survival for melanoma patients; they later confirmed this finding in a larger retrospective study in 2004 (6, 7). These findings have since been confirmed by other groups, and mitotic rate is now included in the latest version of the American Joint Committee on Cancer’s Melanoma Staging System (8).
• Institute researchers are playing a key role in important international clinical trials, such as the Multicentre Selective Lymphadenectomy Trials I and II, and the trials of BRAF inhibiting drugs, which are showing promise in improving the survival of patients with metastatic melanoma.  These studies are contributing to important new understandings in the prognosis of melanoma patients (9, 10). 

REFERENCES

1. McGovern VJ, Mihm MC, Jr., Bailly C, Booth JC, Clark WH, Jr., Cochran AJ, Hardy EG, Hicks JD, Levene A, Lewis MG, Little JH, Milton GW. The classification of malignant melanoma and its histologic reporting. Cancer 1973;32:1446-1457

2. McGovern VJ, Shaw HM, Milton GW, Farago GA. Prognostic significance of the histological features of malignant melanoma. Histopathology 1979;3:385-393

3. Kroon HM, Thompson JF. Isolated limb infusion: A review. J Surg Oncol 2009

4. Thompson JF, Uren RF, Shaw HM, McCarthy WH, Quinn MJ, O'Brien CJ, Howman-Giles RB. Location of sentinel lymph nodes in patients with cutaneous melanoma: new insights into lymphatic anatomy. J Am Coll Surg 1999;189:195-204

5. Thompson JF, Shaw HM, Stretch JR, McCarthy WH, Milton GW. The Sydney Melanoma Unit--a multidisciplinary melanoma treatment center. Surg Clin North Am 2003;83:431-451

6. Azzola MF, Shaw HM, Thompson JF, Soong SJ, Scolyer RA, Watson GF, Colman MH, Zhang Y. Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center. Cancer 2003;97:1488-1498

7. Francken AB, Shaw HM, Thompson JF, Soong SJ, Accortt NA, Azzola MF, Scolyer RA, Milton GW, McCarthy WH, Colman MH, McGovern VJ. The prognostic importance of tumor mitotic rate confirmed in 1317 patients with primary cutaneous melanoma and long follow-up. Ann Surg Oncol 2004;11:426-433

8. Thompson JF, Soong SJ, Balch CM, Gershenwald JE, Ding S, Coit DG, Flaherty KT, Gimotty PA, Johnson T, Johnson MM, Leong SP, Ross MI, Byrd DR, Cascinelli N, Cochran AJ, Eggermont AM, McMasters KM, Mihm MC, Jr., Morton DL, Sondak VK. 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

9. Long GV, Menzies AM, Nagrial AM, Haydu LE, Hamilton AL, Mann GJ, Hughes TM, Thompson JF, Scolyer RA, Kefford RF. Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma. J Clin Oncol 2011;29:1239-1246

10. Thompson JF, Shaw HM. Benefits of sentinel node biopsy for melanoma: a review based on interim results of the first Multicenter Selective Lymphadenectomy Trial. ANZ J Surg 2006;76:100-103