For 30 years, this Program Project Grant (PPG) has pioneered new surgical, immunologic, histopathologic and molecular approaches to diagnosis and prognosis of patients with melanoma. Sentinel node biopsy (SNB), now standard for melanoma and breast cancer, was developed under this PPG;its accuracy for staging melanoma was confirmed during the current funding period (first Multicenter Selective Lymphadenectomy Trial, MSLT-I);and its therapeutic potential without further nodal dissection will be determined by continued accrual and randomization of subjects for MLST-II (Project Ill). Project III continues the follow-up of subjects in MSLT-I to determine if the long-term follow-up reveals a significant difference in melanoma specific survival, in addition to the documented improvement in disease-free survival. Project I will provide the histopathology quality review for these two phase III trials, and Project II will provide the molecular data required for stratification of patients in MSLT-II (first use of qRT-PCR to guide therapy in an international trial). As part of this PPG's commitment to translational research and multidisciplinary integration, Projects I, II, III, &Core A will collaborate in the development of a comprehensive prognostic index based on characteristics of primary tumor, immune microenvironment of SN, and serum assays of antibody, mRNA and DNA biomarkers. Specimens from MSLT and non-MSLT studies will be used to develop and assess new molecular biomarkers (Projects II and Ill) and to investigate histopathologic markers relating to SN tumor burden, architecture, and microenvironment (Projects I and Ill). These markers enable us to determine the likelihood of metastasis beyond the SN and thereby identify candidates for CLND and adjuvant therapy. Projects I and III also investigate the biology and pathophysiology of the SN, while Projects I, II and III, with the help of Core C (Molecular Diagnostics and Support) will develop molecular and immunologic markers for detection of occult systemic metastases. These studies are designed directly together with Core A (Biostatistics). Core B (Administration and Multicenter Trial Operations Center) is a unique, complex core in charge with the administration of the grant and the operations center of the two major Phase III clinical trials.

Public Health Relevance

The overall goal of this Program Project uses melanoma as a model to improve the survival of melanoma patients and those with other solid neoplasms, through optimal surgical management, accurate staging, earl] identification of recurrence, and individualized assessment of prognosis.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (M1))
Program Officer
Wu, Roy S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
John Wayne Cancer Institute
Santa Monica
United States
Zip Code
Jones, Maris S; Lee, Jihey; Stern, Stacey L et al. (2017) Is Pregnancy-Associated Melanoma Associated with Adverse Outcomes? J Am Coll Surg 225:149-158
Faries, Mark B; Thompson, John F; Cochran, Alistair J et al. (2017) Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med 376:2211-2222
Ozao-Choy, Junko; Nelson, Daniel W; Hiles, Jason et al. (2017) The prognostic importance of scalp location in primary head and neck melanoma. J Surg Oncol 116:337-343
Karakousis, Giorgos; Gimotty, Phyllis A; Bartlett, Edmund K et al. (2017) Thin Melanoma with Nodal Involvement: Analysis of Demographic, Pathologic, and Treatment Factors with Regard to Prognosis. Ann Surg Oncol 24:952-959
Jones, Maris S; Torisu-Itakura, Hitoe; Flaherty, Devin C et al. (2016) Second Primary Melanoma: Risk Factors, Histopathologic Features, Survival, and Implications for Follow-Up. Am Surg 82:1009-1013
Faries, Mark B (2016) Intralesional Immunotherapy for Metastatic Melanoma: The Oldest and Newest Treatment in Oncology. Crit Rev Oncog 21:65-73
Ono, Shigeshi; Oyama, Takashi; Lam, Stella et al. (2015) A direct plasma assay of circulating microRNA-210 of hypoxia can identify early systemic metastasis recurrence in melanoma patients. Oncotarget 6:7053-64
Wang, Jinhua; Huang, Sharon K; Marzese, Diego M et al. (2015) Epigenetic changes of EGFR have an important role in BRAF inhibitor-resistant cutaneous melanomas. J Invest Dermatol 135:532-541
Cochran, Alistair J; Huang, Rong-Rong; Su, Albert et al. (2015) Is sentinel node susceptibility to metastases related to nodal immune modulation? Cancer J 21:39-46
Marzese, Diego M; Huang, Sharon K; Hoon, Dave S B (2015) In Situ Sodium Bisulfite Modification of Genomic DNA from Microdissected Melanoma Paraffin-Embedded Archival Tissues. Methods Mol Biol :

Showing the most recent 10 out of 256 publications