Thin cutaneous malignant melanomas (?1.5 mm)

Abstract

BACKGROUND Although thin cutaneous melanomas generally have a favorable prognosis, in some cases they may undergo progression. The current study was undertaken to identify variables that may predict a more aggressive clinical outcome in these patients. In addition to classic clinicopathologic features, the authors tested the prognostic impact of three new morphometric quantitative parameters: 1) tumor thickness plus regression thickness (T+R), 2) percentage of skin thickness infiltrated by tumor cells (T/S ratio), and 3) percentage of skin thickness infiltrated by tumor cells and regression ([T+R]/S ratio). METHODS The authors retrospectively evaluated 287 patients with invasive cutaneous melanoma ≤ 1.5 mm in thickness. Disease free survival rates (Kaplan–Meier method) were compared by using the log rank test. A multivariate analysis (Cox proportional hazards model) was used to determine the independent effect of each variable on progression. Progression was defined as any documented cutaneous local and/or distant metastasis. RESULTS Thirty‐two of the 287 patients (11.1%) underwent disease progression. The overall 5‐year and 10‐year disease free survival rates were 89.3% and 84.6%, respectively. In the univariate analysis, the following factors were found to be significant predictors of progression: male gender (P = 0.01), acral‐lentiginous histotype (P = 0.02), tumor thickness (P = 0.005), T+R (P = 0.001), T/S ratio ≥ 50% (P = 0.03), (T+R)/S ratio ≥ 50% (P = 0.006), vertical growth phase (P = 0.04), and absence of inflammatory response (P < 0.0001). Conversely, age, site, and Clark's level did not affect the risk of recurrences and/or metastases significantly. In the multivariate analysis, only T+R (P = 0.009) and inflammatory response (P < 0.0001) were found to be independent predictors of progression. Five‐year disease free survival rates according to presence versus absence of inflammatory response were 93.4% and 63.8%, respectively (P < 0.0001). CONCLUSIONS In the current study, peritumoral and intratumoral inflammatory infiltrate and T+R were found to be strong independent predictors of progression in thin cutaneous melanomas. Cancer 1999;85:1067–76. © 1999 American Cancer Society.

Functional role of MIA in melanocytes and early development of melanoma

“…Interestingly, several genes known to be important and strongly overexpressed in malignant melanoma were shown to be downregulated in MIA-deficient cell clones: t-PA, SPARC (BM40, osteonectin), MT1-MMP, integrin b3 and fibronectin. A large body of evidence suggests a role for t-PA (Saksela et al, 1984;Meissauer et al, 1991;Alizadeh et al, 1995;de Vries et al, 1996), SPARC (Ledda et al, 1997a, b;Massi et al, 1999;Sturm et al, 2002), MT1-MMP (Hofmann et al, 2000a, b;Seftor et al, 2001;Krengel et al, 2002;Sounni et al, 2002;Iida et al, 2004), integrin b3 (Nip et al, 1992;Natali et al, 1995;Van Belle et al, 1999;Felding-Habermann et al, 2002;Sturm et al, 2002) and fibronectin (Wollina et al, 1991;Natali et al, 1995) in migration, invasion and metastatic spread of melanoma cells. Since these proteins are directly or indirectly involved in matrix degradation (t-PA, MT1-MMP), in the transition of melanomas being in radial growth phase to a vertical growth phase (induction of SPARC by integrin b3) and enforced cell proliferation (fibronectin), induction of gene expression by MIA could account for several abilities that melanoma cells harbor during tumor development and progression.…”

Expression of polo‐like kinase (PLK1) in thin melanomas: a novel marker of metastatic disease

“…Several investigators reported that thin melanomas, which should have an excellent prognosis according to the Breslow index, may have the potential to metastasize, some in a very rapid fashion (Table 1). 5–13 Identifying high‐risk and low‐risk patients with thin melanomas may improve guidelines for the application of adjuvant therapies or a long‐term follow‐up to this population 7 . However, appropriate markers to measure the aggressive behavior of thin melanomas were missing.…”

“…They may have the potential to develop recurrence and metastasize despite a favorable Breslow thickness (Table 1). 5–13 Therefore, better prognostic tools are required to identify melanomas with high metastatic potential.…”

SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor–stromal interactions

“…Secreted protein acidic and rich in cysteine (SPARC)/ osteonectin/BM 40 is a matricellular glycoprotein involved in diverse biological processes, including tissue remodeling, wound repair, morphogenesis, cellular differentiation, cell proliferation, cell migration, and angiogenesis (Jendraschak and Sage, 1996;Yan and Sage, 1999;Bradshaw and Sage, 2001;Brekken and Sage, 2001). SPARC is highly expressed in a wide range of human malignant neoplasms, and the deregulated expression of SPARC is often correlated with disease progression and/or poor prognosis (Wewer et al, 1988;Bellahcene and Castronovo, 1995;Porte et al, 1995;Porter et al, 1995Porter et al, , 1998Ledda et al, 1997;Massi et al, 1999;Rempel et al, 1999;Thomas et al, 2000;Yamanaka et al, 2001). Interestingly, in certain tumor types, strong expression of SPARC has been detected predominantly in the stroma adjacent to the neoplastic cells (Le Bail et al, 1999;Paley et al, 2000;Iacobuzio-Donahue et al, 2002a).…”