Protein S100 as Prognostic Marker for Gastrointestinal Stromal Tumors: A Clinicopathological Risk Factor Analysis

Abstract

Gastrointestinal stromal tumors (GISTs) are a heterogenous group of mesenchymal neoplasms ranging from semibenign tumors to highly aggressive neoplasms. Predicting their clinical behavior is challenging and criteria delineating benign from malignant cases are controversially discussed. The aims of the present study were to define the clinicopathological features of 35 GISTs and to determine whether any specific parameters were associated with the patient's outcome. In the present series, protein S100 (S100) expression was found in 13/35 (37%) patients with a varying staining intensity ranging between strong and moderate. The multivariate statistical analysis in the S100-positive group revealed a significantly poorer survival (p = .0058) and a tendency for higher recurrence (p = .052) compared to the negative GIST patients. Furthermore, the statistical analysis disclosed a correlation between the expression of CD117, CD34, desmin, and alpha-smooth muscle actin and survival or recurrence (p > .05). Positive immunoreactivity was seen for CD117 in 25 (71%) patients and for CD34 in 19 (54%) patients. In addition we confirmed the previously reported impact of initial tumor size on survival and recurrence rate (p = .034 and p = .039). The series was also analyzed according to established prognostic factors (tumor size and mitotic activity), which indicated that 77% of S100-positive cases were at high risk for malignant tumor behavior, 15% at intermediate risk, and 8% at low risk. Based on these findings, we suggest that protein S100 represents an additional prognostic factor to better define the malignant potential of GISTs and stratify the risk for each patient.

Does Immunohistochemistry Provide Additional Prognostic Data in Gastrointestinal Stromal Tumors?

“…Similar with other markers, no association was reported between S-100 immunoexpression and GIST prognosis in several retrospective studies. However, only two studies proposed that S-100 expression had a negative prognostic effect on GISTs (Fujimoto et al, 2003;Perez et al, 2007). In our study group, both S-100 and desmin were not associated with GIST prognosis relevant with the results of the great majority of the studies.…”

Multiple S100 protein isoforms and C-terminal phosphorylation contribute to the paralog-selective regulation of nonmuscle myosin 2 filaments

“…We expect that other S100 proteins, having the ability to effectively disrupt NM2A filaments, can function similarly to S100A4. In clinical studies, S100A1 (74), S100A2 (75-77), S100A6 (78), S100P (79), (80), and S100B (81) were found to be up-regulated in many tumors, and they are also believed to promote metastasis (82). A similar effect is seen when NM2A is targeted directly.…”

Recidiva en intestino delgado de tumor de GIST de bajo riesgo: Caso clínico y revisión de la literatura

“…Esto se debe a que el anticuerpo MIB-1 reconoce el antígeno nuclear Ki-67, que está asociado con la proliferación celular y que se encuentra a lo largo del ciclo celular (fases G1, S, G2, y M), pero no se encuentra en células en reposo (G0) [19][20][21] (Tabla 2). Por otro lado, Pérez y cols, han descrito que la expresión de la proteína S-100 como marcador inmunohistoquímico revelaría una menor sobrevida y una tendencia a mayor recurrencia que en los tumores negativos para este marcador 22 . En cuanto a estudios genéticos, la presencia de mutaciones específicas en el gen C-KIT podría predecir una menor sobrevida a 5 años luego de la resección quirúrgica en tumores de GIST localizados 23 .…”